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BACKGROUND: The expression efficiency of recombinant adeno-associated virus serotype 9 (rAAV9) carrying the macrophage-specific promoter synthetic promoter 146-C1 (SP146-C1) and the exogenous gene vascular endothelial growth factor C (VEGFC) in atherosclerosis is uncertain. OBJECTIVE: To investigate the expression efficiency of rAAV9-SP146-C1-VEGFC in atherosclerotic mice and its effect on lymphangiogenesis. METHODS: Thirty ApoE-/- mice were fed high-fat diet for 12 weeks to establish atherosclerosis models and were randomly divided into six groups, five in each group: 7-, 14-, 21-, 28-, and 35-day transfection groups and control group. The mice in the transfection groups were transfected with 5.0×1011 vg rAAV9-SP146- C1-VEGFC by caudal vein injection. In the control group, the mice were injected with the same amount of control virus rAAV9-SP146-C1-Scramble. Animals in the first five groups were killed under anesthesia at 7, 14, 21, 28 and 35 days after transfection, respectively, and those in the control group were killed under anesthesia at 7 days. Serum, femur, tibia, heart and aorta tissue samples were collected and retained in each group. The femur and tibia of mice in each group were used to extract bone marrow-derived macrophages. The gene expression of vascular endothelial growth factor C (VEGFC), vascular endothelial growth factor receptor 3 (VEGFR3), Podoplanin and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) in bone marrow-derived macrophages and the aorta were detected by RT-qPCR. VEGFC protein expression levels in bone marrow-derived macrophages and the aorta were detected by western blot, serum level of VEGFC was detected by ELISA, and VEGFC expression in the aortic sinus and LYVE-1 expression around the aorta and in the myocardium was detected by immunofluorescence. RESULTS AND CONCLUSION: The serum level of VEGFC, the mRNA expression of VEGFC, VEGFR3, Podoplanin, and LYVE-1 in bone marrow-derived macrophages and the aorta, the protein expression of VEGFC in bone marrow-derived macrophages, and the fluorescence intensity of VEGFC in aortic sinus plaques were significantly increased in the 7-day transfection group compared with the control group (P < 0.05, P < 0.01). Serum VEGFC level of mice transfected with rAAV9- SP146-C1-VEGFC gradually increased with time and began to decrease at 28 days. mRNA levels of VEGFC, VEGFR3, Podoplanin and LYVE-1 in mouse aorta and bone marrow-derived macrophages, VEGFC protein level in bone marrow-derived macrophages, VEGFC fluorescence intensity in aortic sinus plaques, LYVE1 fluorescence intensity around the aortic sinus and in the myocardium gradually increased with time (P < 0.05). In addition, the mRNA level of LYVE-1 in the aorta and the fluorescence intensity of LYVE-1 around the aortic sinus and in the myocardium were the highest at 28 days (P < 0.05), and gradually decreased (P < 0.05). The expression of the other indicators reached the peak at 21 days. To conclude, rAAV9-SP146-C1-VEGFC could effectively transfect bone marrowderived macrophages and promote lymphatic hyperplasia in atherosclerotic mice. [ABSTRACT FROM AUTHOR]

To examine the association between cerebral artery stenosis and depressive symptoms in elderly patients. The study participants were 365 patients aged ≥65 years who visited the psychiatric outpatient clinic, Samsung Medical Center between January 1, 2000, and December 31, 2019, and were diagnosed with depressive disorder. They had brain imaging tests including magnetic resonance angiography (MRA), psychological evaluations including the 15-item Geriatric Depression Scale (GDS-15), and lab tests. Individuals' cerebral artery stenosis was identified and the association with significant depressive symptoms was examined. Of the 365 subjects, 108 had at least one location of cerebral artery stenosis (29.6 %). The mean score of GDS-15 in the stenosis group was 8.1 (SD, 3.8), higher than the mean GDS-15 score of 6.5 (SD, 4.0) for the group without stenosis (p < 0.001). Compared to no middle cerebral artery (MCA) stenosis, having MCA stenosis was associated with significant depressive symptoms (p = 0.005). Compared to no posterior cerebral artery (PCA) stenosis, having left PCA stenosis was associated with significant depressive symptoms (p = 0.022). In the multivariable linear regression analysis, only bilateral MCA stenosis had a positive association with the score of GDS-15 (p = 0.013). Bilateral MCA stenosis and left PCA stenosis are associated with significant depressive symptoms among elderly patients, with bilateral MCA stenosis positively associated with the severity of depression. • Cerebral artery stenosis was associated with depressive symptoms among elderly patients. • Bilateral middle cerebral artery stenosis was associated with significant depressive symptoms and the severity. • Left posterior cerebral artery stenosis was associated with significant depressive symptoms. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is the pathologic basis of many cardiovascular diseases (CVDs). Hydroxysafflor yellow A (HSYA) is a valuable natural food pigment that has been reported to have significant health‐promoting abilities. However, the anti‐AS efficacy and mechanisms of HSYA have not yet been characterized. Here, we found that treatment of apolipoprotein A (ApoE) knockout (ApoE−/−) mice with HSYA markedly ameliorated atherosclerosis evidenced by decreased levels of lipids, sphingosine‐1‐phosphate (S1P), inflammatory factors, oxidative stress, vascular endothelial permeability, and endothelial damage. Moreover, mechanistic studies revealed that HSYA treatment downregulated the expression of aortic sphingosine kinase 1 (SphK1), sphingosine‐1‐phosphate receptor 3 (S1PR3), Ras homolog family member A (RhoA), Rho‐associated coiled‐coil containing protein kinase (ROCK), and filamentous actin (F‐actin). The results of administration with HSYA reversed the effects of SphK1 agonist and S1PR3 agonist on oxidized low‐density lipoprotein (ox‐LDL)‐induced vascular endothelial cell migration ability and F‐actin expression, and decreased RhoA/ROCK protein expression further confirmed the conclusion that HSYA reduced vascular endothelial permeability by modulating the SphK1/S1P/S1PR3/RhoA/ROCK signaling pathway, thereby exerting anti‐atherosclerotic effects. Overall, this study indicated that HSYA might be a therapeutic candidate for the treatment of AS. [ABSTRACT FROM AUTHOR]

AbstractEndothelial dysfunction is a risk factor for atherosclerosis and includes impaired endothelium-dependent vasodilatation. We have shown previously that low density lipoprotein (LDL) can be oxidized by iron in the lysosomes of macrophages. Macrophage lysis in atherosclerotic lesions might expose endothelial cells to this oxidized LDL and adversely affect their function. LDL was oxidized by ferrous sulfate (5 µM) for 24 h at pH 4.5 at 37 °C. Aortas from male Wistar rats were cut into rings and subjected to wire myography for isometric tension recording. The rings were incubated with or without oxidized LDL (50 µg protein/ml) for one hour, constricted with 100 nM phenylephrine and relaxation to acetylcholine (1 nM − 3 µM) was measured. There was about 50% less relaxation in the presence of this oxidized LDL. Endothelial-independent vasodilatation induced by sodium nitroprusside was less affected by oxidized LDL. Oxidized LDL increased the formation of reactive oxygen species by the aortic rings and by cultured human aortic and dermal microvascular endothelial cells, which might have inactivated nitric oxide. Acetylcholine increased the activatory phosphorylation of eNOS (ser-1177), but oxidized LDL had little effect on this activation in cultured human aortic endothelial cells. These findings raise the possibility that LDL oxidized in lysosomes and released from lysed macrophages might decrease vasodilatation in atherosclerotic arteries. [ABSTRACT FROM AUTHOR]

A disbalance between immune regulatory cells and inflammatory cells is known to drive atherosclerosis. However, the exact mechanism is not clear. Here, we investigated the homing of immune regulatory cells, mainly, regulatory T cells (Tregs) and myeloid‐derived suppressor cells (MDSCs) subsets in asymptomatic coronary artery disease (CAD) risk factor‐exposed young individuals (dyslipidemia [DLP] group) and stable CAD patients (CAD group). Compared with healthy controls (HCs), Tregs frequency was reduced in both DLP and CAD groups but expressed high levels of CCR5 in both groups. The frequency of monocytic‐myeloid‐derived suppressor cells (M‐MDSCs) was increased while polymorphonuclear myeloid‐derived suppressor cells (PMN‐MDSCs) were decreased in CAD patients only. Interestingly, although unchanged in frequency, M‐MDSCs of the DLP group expressed high levels of CCR5. Serum levels of chemokines (CCL5, CX3CL1, CCL26) and inflammatory cytokines (IL‐6, IL‐1β, IFN‐γ, TNF‐α) were higher in the DLP group. Stimulation with inflammatory cytokines augmented CCR5 expression in Tregs and M‐MDSCs isolated from HCs. Activated endothelial cells showed elevated levels of CX3CL1 and CCL5 in vitro. Blocking CCR5 with D‐Ala‐peptide T‐amide (DAPTA) increased Treg and M‐MDSC frequency in C57Bl6 mice fed a high‐fat diet. In accelerated atherosclerosis model, DAPTA treatment led to the formation of smooth muscle‐rich plaque with less macrophages. Thus, we show that CCR5‐CCL5 axis is instrumental in recruiting Tregs and M‐MDSCs to dysfunctional endothelium in the asymptomatic phase of atherosclerosis contributing to atherosclerosis progression. Drugs targeting CCR5 in asymptomatic and CAD risk‐factor/s‐exposed individuals might be a novel therapeutic regime to diminish atherogenesis. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic Cardiovascular Disease (ASCVD) is a global public health concern. This study aimed to estimate the healthcare resource utilization (HRU) and costs stratified by cardiovascular disease (CVD) risk categories using real-world evidence, in a regional population in Portugal. Methods: This is a retrospective observational study, using data from Electronic Health Records between 2017 and 2021. Patients aged ≥ 40 years, and with at least one general practitioner (GP) appointment in the 3 years before 31st of December 2019, were included. CVD risk categories were determined based on 2021 ESC prevention guidelines. HRU encompassed hospital data (hospitalizations, outpatient and emergency room visits) and GP appointments. Total direct costs per patient were calculated based on the reference cost of the Portuguese legislation for payment methodology on Diagnosis-Related Groups (DRGs). Results: Analysis of 3 122 695 episodes, revealed consistent HRU and costs across the five years. Very high-risk patients, showed higher HRU, particularly in hospital admissions. Costs tended to rise with higher CVD risk level. Very high-risk patients with ASCVD had higher costs for hospital admissions, while low-to-moderate risk patients had higher costs for GP visits. Despite a smaller proportion, very high-risk patients with prior ASCVD represent the highest costs per patient across healthcare settings (from 115€ in emergency visits to 2 673€ in hospitalizations), followed by very high-risk patients without prior ASCVD (ASCVD-risk equivalents). Conclusion: This study revealed a substantial HRU and costs by patients with very high CVD risk, particularly those with prior ASCVD. Moreover, ASCVD-risk equivalents emerge as notable consumers, emphasizing the importance of risk assessment and preventive measures in cost-effective management of these patients. [ABSTRACT FROM AUTHOR]

Background: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. Methods: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. Results: We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. Conclusion: These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis. [ABSTRACT FROM AUTHOR]

Background and purpose: Cardiovascular risk factors are known to contribute to the formation of atherosclerotic plaques, which can result in carotid stenosis. However, the extent to which these factors are associated with intraplaque neovascularization, a key indicator of plaque vulnerability, remains unclear. To investigate this relationship, a study was conducted utilizing contrast-enhanced ultrasound (CEUS) to assess intraplaque neovascularization in symptomatic patients. Methods: A cohort of 157 symptomatic patients underwent evaluation using Contrast-Enhanced Ultrasound (CEUS) imaging to assess carotid intraplaque neovascularization, which was quantified based on the degree of plaque enhancement. The collected data encompassed baseline patient characteristics, results from biochemical examinations, cardiovascular risk factors, and medication usage history. Regression analyses were conducted to elucidate the relationship between carotid plaque neovascularization and various cardiovascular risk factors. Results: Patients with intraplaque neovascularization were more prone to have diabetes mellitus (OR 3.81, 95% CI 1.94-7.46, p < 0.001), dyslipidemia (OR 2.36, 95% CI 1.22-4.55, p = 0.011) and hypertension (OR 2.92, 95% CI 1.50-5.71, p = 0.002). Smoking increased the risk of having intraplaque neovascularization (OR 2.25, 95% CI 1.12-4.54, p = 0.023). Treatment with statins was significantly lower in patients with intraplaque neovascularization (OR 0.37, 95% CI 0.19-0.72, p = 0.003). In the multivariate analysis, diabetes mellitus (OR 3.27, 95% CI 1.10-9.78, p = 0.034) was independently related to the presence of intraplaque neovascularization. Meanwhile, compared to the patients in the first tertile of serum glucose (< 6.20 mmol/L), the patients in the third tertile (> 13.35 mmol/L) had the most significance of intraplaque neovascularization (OR 5.55, 95% CI 1.85-16.66, p = 0.002). Conclusion: The findings indicated that diabetes mellitus is a significant cardiovascular risk factor that is strongly associated with carotid intraplaque neovascularization. [ABSTRACT FROM AUTHOR]

Background: Chrysin, a polyphenolic compound, possesses antioxidant and anti-inflammatory properties. In this study, we investigated the effect of chrysin on the expression of A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), a protease enzyme involved in degrading extracellular matrix associated with atherosclerosis. Methods and Results: We have studied the cell viability by MTT assay and foam cell formation by oil red O staining. The mRNA and protein expression of ADAMTS-4 was studied using quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. Our study showed that chrysin significantly downregulates the expression of ADAMTS-4 in foam cells. Conclusion: Chrysin's ability to downregulate the expression of ADAMTS-4, a protease involved in degrading the extracellular matrix, bestows upon it a new therapeutic potential for managing atherosclerosis. Highlights: Chrysin downregulates the mRNA and protein expression of ADAMTS-4 in foam cells. [ABSTRACT FROM AUTHOR]

Introduction: Recent progress in cell isolation technologies and high-end omic technologies has allowed investigation of single cell sets across multiple omic domains and a thorough exploration of cellular function and various functional stages. While most multi-omic studies focused on dual RNA and protein analysis of single cell population, it is crucial to include lipid and metabolite profiling to comprehensively elucidate molecular mechanisms and pathways governing cell function, as well as phenotype at different functional stages. Methods: To address this gap, a cellular lipidomics and transcriptomics phenotyping approach employing simultaneous extraction of lipids, metabolites, and RNA from single cell populations combined with untargeted cellular 4 dimensional (4D)-lipidomics profiling along with RNA sequencing was developed to enable comprehensive multi-omic molecular profiling from the lowest possible number of cells. Reference cell models were utilized to determine the minimum number of cells required for this multi-omics analysis. To demonstrate the feasibility of higher resolution cellular multi-omics in earlystage identification of cellular phenotype changes in pathological and physiological conditions we implemented this approach for phenotyping of macrophages in two different activation stages: MyD88-knockout macrophages as a cellular model for atherosclerosis protection, and wild type macrophages. Results and Discussion: This multi-omic study enabled the determination of the lipid content remodeling in macrophages with anti-inflammatory and atherosclerotic protective function acquired by MyD88-KO, hence expedites the understanding of the molecular mechanisms behind immune cells effector functionality and of possible molecular targets for therapeutic intervention. An enriched functional role of phosphatidylcholine and plasmenyl/plasmalogens was shown here to accompany genetic changes underlying macrophages acquisition of anti-inflammatory function, finding that can serve as reference for macrophages reprogramming studies and for general immune and inflammation response to diseases. [ABSTRACT FROM AUTHOR]

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder that causes severe cardiovascular disease, resulting in the death of patients in their teenage years. The disease pathology is caused by the accumulation of progerin, a mutated form of the nuclear lamina protein, lamin A. Progerin binds to the inner nuclear membrane, disrupting nuclear integrity, and causes severe nuclear abnormalities and changes in gene expression. This results in increased cellular inflammation, senescence, and overall dysfunction. The molecular mechanisms by which progerin induces the disease pathology are not fully understood. Progerin's detrimental impact on nuclear mechanics and the role of the nucleus as a mechanosensor suggests dysfunctional mechanotransduction could play a role in HGPS. This is especially relevant in cells exposed to dynamic, continuous mechanical stimuli, like those of the vasculature. The endothelial (ECs) and smooth muscle cells (SMCs) within arteries rely on physical forces produced by blood flow to maintain function and homeostasis. Certain regions within arteries produce disturbed flow, leading to an impaired transduction of mechanical signals, and a reduction in cellular function, which also occurs in HGPS. In this review, we discuss the mechanics of nuclear mechanotransduction, how this is disrupted in HGPS, and what effect this has on cell health and function. We also address healthy responses of ECs and SMCs to physiological mechanical stimuli and how these responses are impaired by progerin accumulation. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Elevated levels of 5‐HT have been correlated with coronary artery disease and cardiac events, suggesting 5‐HT is a potential novel factor in the development of atherosclerotic cardiovascular disease. However, the underlying pathological mechanisms of the 5‐HT system in atherosclerosis remain unclear. The 5‐HT2B receptor (5‐HT2BR), which establishes a positive feedback loop with 5‐HT, has been identified as a contributor to pathophysiological processes in various vascular disorders. In this study, we investigated the immunological impact of 5‐HT2BR in atherosclerosis‐prone apolipoprotein E‐deficient (ApoE−/−) mice.Plasma levels of 5‐HT were measured in mice using an ELISA kit. Atherosclerotic plaque formation, macrophage infiltration and inflammatory signalling were assessed in ApoE−/− mice by employing both pharmacological inhibition and genetic deficiency of 5‐HT2BR. Inflammasome activation was elucidated using peritoneal macrophages isolated from 5‐HT2BR‐deficient mice.An upregulation of 5‐HT2BR expression was observed in the aortas of ApoE−/− mice, exhibiting a strong correlation with the presence of macrophages in plaques. Atherosclerosis was attenuated in mice through pharmacological inhibition and genetic deficiency of 5‐HT2BR. Additionally, a significant reduction in atherosclerotic plaque size was achieved through bone marrow reconstitution with 5‐HT2BR‐deficient cells. 5‐HT2BR‐deficient macrophages showed attenuated interferon (IFN) signalling, NLRP3 inflammasome activation, and interleukin‐1β release. Moreover, macrophages primed with 5‐HT2BR deficiency displayed an anti‐inflammatory phenotype.These findings support the hypothesis that 5‐HT2BR in macrophages plays a causal role in the development of atherosclerosis, revealing a novel perspective for potential therapeutic strategies in atherosclerosis‐related diseases. [ABSTRACT FROM AUTHOR]

Background and purpose Experimental approach Key results Conclusion and implications Atherosclerosis is the basis of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by lipid peroxidation, which contributes to atherogenesis. The plant extract PNS (Panax notoginseng saponins), containing the main active ingredients of Panax notoginseng, exhibits anti‐atherogenic properties. Herein, we determined whether PNS and its major components could attenuate atherosclerosis by suppressing ferroptosis and revealed the underlying mechanism(s).The anti‐atherogenic effects of PNS and their association with inhibition of ferroptosis was determined in apoE−/− mice. In vitro, the anti‐ferroptotic effect and mechanism(s) of PNS components were demonstrated in the presence of ferroptosis inducers. Expression of ferroptosis markers and the ubiquitination of Keap1 were evaluated in USP2−/− macrophages. Finally, the anti‐atherogenic effect of USP2 knockout was determined by using USP2−/− mice treated with high‐fat diet (HFD) and AAV‐PCSK9.PNS inhibited ferroptosis and atherosclerosis in vivo. PNS suppressed ferroptosis and ferroptosis‐aggravated foam cell formation and inflammation in vitro. Mechanistically, PNS and its components activated Nrf2 by antagonizing Keap1, which was attributed to the inhibition of USP2 expression. USP2 knockout antagonized ferroptosis and ferroptosis‐aggravated foam cell formation and inflammation, thus mitigating atherosclerosis. USP2 knockout abolished inhibitory effects of PNS on foam cell formation and inflammation in vitro.PNS reduced USP2‐mediated Keap1 de‐ubiquitination and promoted Keap1 degradation, thereby activating Nrf2, improving iron metabolism and reducing lipid peroxidation, thus contributing to an anti‐atherosclerotic outcome. Our study revealed the mechanism(s) underlying inhibition of ferroptosis and atherosclerosis by PNS. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to reveal the role and mechanism of MG-132 in delaying hyperlipidemia-induced senescence of vascular smooth muscle cells (VSMCs). Methods: Immunohistochemistry and hematoxylin-eosin staining confirmed the therapeutic effect of MG-132 on arterial senescence in vivo and its possible mechanism. Subsequently, VSMCs were treated with sodium palmitate (PA), an activator (Recilisib) or an inhibitor (Pictilisib) to activate or inhibit PI3K, and CCK-8 and EdU staining, wound healing assays, Transwell cell migration assays, autophagy staining assays, reactive oxygen species assays, senescence-associated β-galactosidase staining, and Western blotting were performed to determine the molecular mechanism by which MG-132 inhibits VSMC senescence. Validation of the interaction between MG-132 and PI3K using molecular docking. Results: Increased expression of p-PI3K, a key protein of the autophagy regulatory system, and decreased expression of the autophagy-associated proteins Beclin 1 and ULK1 were observed in the aortas of C57BL/6J mice fed a high-fat diet (HFD), and autophagy was inhibited in aortic smooth muscle. MG-132 inhibits atherosclerosis by activating autophagy in VSMCs to counteract PA-induced cell proliferation, migration, oxidative stress, and senescence, thereby inhibiting VSMC senescence in the aorta. This process is achieved through the PI3K/AKT/mTOR signaling pathway. Conclusion: MG-132 activates autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby inhibiting palmitate-induced proliferation, migration, and oxidative stress in vascular smooth muscle cells and suppressing their senescence. [ABSTRACT FROM AUTHOR]

Background: NOD-like receptor protein 3 (NLRP3) inflammasome activation is indispensable for atherogenesis. Mitophagy has emerged as a potential strategy to counteract NLRP3 inflammasome activation triggered by impaired mitochondria. Our previous research has indicated that dihydromyricetin, a natural flavonoid, can mitigate NLRP3-mediated endothelial inflammation, suggesting its potential to treat atherosclerosis. However, the precise underlying mechanisms remain elusive. This study sought to investigate whether dihydromyricetin modulates endothelial mitophagy and inhibits NLRP3 inflammasome activation to alleviate atherogenesis, along with the specific mechanisms involved. Methods: Apolipoprotein E-deficient mice on a high-fat diet were administered daily oral gavages of dihydromyricetin for 14 weeks. Blood samples were procured to determine the serum lipid profiles and quantify proinflammatory cytokine concentrations. Aortas were harvested to evaluate atherosclerotic plaque formation and NLRP3 inflammasome activation. Concurrently, in human umbilical vein endothelial cells, Western blotting, flow cytometry, and quantitative real-time PCR were employed to elucidate the mechanistic role of mitophagy in the modulation of NLRP3 inflammasome activation by dihydromyricetin. Results: Dihydromyricetin administration significantly attenuated NLRP3 inflammasome activation and vascular inflammation in mice on a high-fat diet, thereby exerting a pronounced inhibitory effect on atherogenesis. Both in vivo and in vitro, dihydromyricetin treatment markedly enhanced mitophagy. This enhancement in mitophagy ameliorated the mitochondrial damage instigated by saturated fatty acids, thereby inhibiting the activation and nuclear translocation of NF-κB. Consequently, concomitant reductions in the transcript levels of NLRP3 and interleukin-1β (IL-1β), alongside decreased activation of NLRP3 inflammasome and IL-1β secretion, were discerned. Notably, the inhibitory effects of dihydromyricetin on the activation of NF-κB and subsequently the NLRP3 inflammasome were determined to be, at least in part, contingent upon its capacity to promote mitophagy. Conclusion: This study suggested that dihydromyricetin may function as a modulator to promote mitophagy, which in turn mitigates NF-κB activity and subsequent NLRP3 inflammasome activation, thereby conferring protection against atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory condition of the arteries and represents the primary cause of various cardiovascular diseases. Despite ongoing progress, finding effective anti-inflammatory therapeutic strategies for atherosclerosis remains a challenge. Here, we assessed the potential of molecular magnetic resonance imaging (MRI) to visualize the effects of 01BSUR, an anti-interleukin-1β monoclonal antibody, for treating atherosclerosis in a murine model. Male apolipoprotein E-deficient mice were divided into a therapy group (01BSUR, 2 × 0.3 mg/kg subcutaneously, n = 10) and control group (no treatment, n = 10) and received a high-fat diet for eight weeks. The plaque burden was assessed using an elastin-targeted gadolinium-based contrast probe (0.2 mmol/kg intravenously) on a 3 T MRI scanner. T1-weighted imaging showed a significantly lower contrast-to-noise (CNR) ratio in the 01BSUR group (pre: 3.93042664; post: 8.4007067) compared to the control group (pre: 3.70679168; post: 13.2982156) following administration of the elastin-specific MRI probe (p < 0.05). Histological examinations demonstrated a significant reduction in plaque size (p < 0.05) and a significant decrease in plaque elastin content (p < 0.05) in the treatment group compared to control animals. This study demonstrated that 01BSUR hinders the progression of atherosclerosis in a mouse model. Using an elastin-targeted MRI probe, we could quantify these therapeutic effects in MRI. [ABSTRACT FROM AUTHOR]

Carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis, has been found to be associated with incident stroke. High-sensitivity C-reactive protein (CRP) and fibrinogen have been demonstrated to be associated with atherosclerosis. Previous studies on heritability estimates of IMT, CRP, and fibrinogen among Chinese populations are limited. This study aims to estimate the heritability of these risk factors in residents who participated in the Taichung Community Health Study (TCHS) and their family members. A total of 2671 study subjects from 805 families were enrolled in the study, selected from a random sample of TCHS participants and their family members. CRP, and fibrinogen were obtained from each participant, and a questionnaire interview was conducted. cIMT was measured by high-resolution B-mode ultrasound and expressed as the mean of the maximum. Heritability estimates and the familial correlation of cIMT, CRP, and fibrinogen among family pairs were determined with SAGE software. With multivariate adjustments, significant heritability was found for cIMT (h2 = 0.26, P < 0.001), CRP (h2 = 0.34, P < 0.001), and fibrinogen (h2 = 0.48, P < 0.001). The intrafamilial correlation coefficients for the three indexes in the parent–offspring pairs were significant (P < 0.001) and ranged from 0.17 to 0.41. The full sibship correlations were also significant (P < 0.001) for the three indexes and ranged from 0.19 to 0.47. This study indicates that a moderate proportion of the variability in CRP, fibrinogen, and cIMT can be attributed to genetic factors in Chinese populations. The findings suggest that CRP is associated with cIMT, whereas no significant association exists between fibrinogen and cIMT. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) modification stands out among various RNA modifications as the predominant form within eukaryotic cells, influencing numerous cellular processes implicated in disease development. m6A modification has gained increasing attention in the development of atherosclerosis and has become a research hotspot in recent years. Programmed cell death (PCD), encompassing apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, plays a pivotal role in atherosclerosis pathogenesis. In this review, we delve into the intricate interplay between m6A modification and diverse PCD pathways, shedding light on their complex association during the onset and progression of atherosclerosis. Clarifying the relationship between m6A and PCD in atherosclerosis is of great significance to provide novel strategies for cardiovascular disease treatment. [ABSTRACT FROM AUTHOR]

Introduction: The advent of high-sensitivity C-reactive protein (Hs-CRP) assays has enhanced the utility of this acute-phase reactant in forecasting initial cardiovascular events. Elevated HsCRP levels are partially indicative of the extent of myocardial injury and can serve as predictors of both short-term and long-term outcomes in patients experiencing acute myocardial infarction. The study aims to investigate the relationship between elevated Hs-CRP levels and various traditional risk factors, including age, sex, lifestyle, and comorbidities. Materials and Methods: A prospective cross-sectional study involving 123 patients with traditional risk factors and pre-existing cardiovascular conditions was conducted at a tertiary care center. Hs-CRP levels were measured using immunoturbidimetric methods, and statistical correlations were performed. The statistical analysis was carried out using SPSS version 21 software. Results: Out of 123 patients, 82 had Hs-CRP levels exceeding 3 mg/L, while 41 patients had HsCRP levels below 3 mg/L. A total of 36.59% of the patients were in the age group of 51–60 years, with the majority (78.05%) being male. Among the individual lifestyle factors and traditional risk factors evaluated, five parameters—sedentary lifestyle, smoking, pre-existing hypertension, diabetes mellitus, and electrocardiographic changes—were found to be statistically significant. The correlation between elevated Hs-CRP levels and cardiovascular disease was also statistically significant. Conclusion: Hs-CRP is an independent biomarker for cardiovascular disease, with a significant positive correlation established between elevated Hs-CRP levels and major traditional risk factors such as sedentary lifestyle, smoking, hypertension, and diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objectives:We aimed to study the impact of gout as a correlative risk factor in the incidence of acute myocardial infarction (AMI) among patients without known MI risk factors. Our study population was obtained from the National Inpatient Sample (NIS) 2011-2018 using the International Classification of Diseases, Ninth and Tenth Revisions. Methods: This study included patients without cardiovascular disease (CVD), and various outcomes were compared among patients with and without gout. Cohorts were weighted using an algorithm provided by the NIS, which allows for national estimates. Our primary endpoint was the odds of developing an MI, and secondary endpoints were adverse hospital events and length of stay. In total, 117,261,842 patients without CVD risk factorswere included in this study, 187,619 (0.16%) of whom had a diagnosis of gout. Results: Patients without CVD risk factors who had gout were older and more likely to be male compared with patients without gout. Among patients without CVD risk factors, the odds of having an AMI were significantly higher in those with gout compared with those without, even after adjusting for chronic nonsteroidal anti-inflammatory drug and oral steroid use. Moreover, patients without CVD risk factors and with gout were more likely to develop acute renal failure, acute thromboembolic event, shock, acute gastrointestinal bleed, and arrhythmia compared with those without gout. Furthermore, patients without CVD risk factors who were admitted with gout had higher mortality compared with those without gout. Conclusions: In our study, we found that patients without risk factors forAMI who had goutwere more likely to develop AMI compared with those without gout. Furthermore, the same patients were more likely to develop other adverse outcomes. Even with proper management, these individuals should be monitored closely for coronary events. [ABSTRACT FROM AUTHOR]

Curcumin potentiates the stabilization of atherosclerotic plaques by polarizing macrophages, but its non-specific targeting hinders its clinical application. We aim to harness multifunctional lipid nanoparticles (MLNPs) to facilitate the imaging and targeted delivery of curcumin specifically to inflammatory macrophages, counteracting vulnerable plaques and mitigating the risk of ischemic events. Cholesteryl-9-carboxynonanoate-(125I‑iron oxide nanoparticle/Curcumin)-lipid-coated nanoparticles [9-CCN-(125I-ION/Cur)-LNPs], namely MLNPs, are designed to carry hybrid imaging agents. These agents combine 125I-ION with lipids containing phagocytic 'eat-me' signals, inducing macrophages to engulf the MLNPs. Our research demonstrates that the designed MLNPs accurately accumulate at unstable plaques and are precisely visualized and highlighted by both SPECT and MRI. Furthermore, MLNPs achieve high efficiency in delivering 125I-ION and curcumin to macrophages, ultimately leading to significant M1-to-M2 macrophage polarization. These real-time imaging and polarization capabilities of plaques have immediate clinical applicability and may pave the way for novel therapies to stabilize unstable atherosclerotic plaques. [Display omitted] [ABSTRACT FROM AUTHOR]

In recent decades, there has been a burgeoning interest in cell membrane coating strategies as innovative approach for targeted delivery systems in biomedical applications. Platelet membrane-coated nanoparticles (PNPs), in particular, are gaining interest as a new route for targeted therapy due to their advantages over conventional drug therapies. Their stepwise approach blends the capabilities of the natural platelet membrane (PM) with the adaptable nature of manufactured nanomaterials, resulting in a synergistic combination that enhances drug delivery and enables the development of innovative therapeutics. In this context, we present an overview of the latest advancements in designing PNPs with various structures tailored for precise drug delivery. Initially, we describe the types, preparation methods, delivery mechanisms, and specific advantages of PNPs. Next, we focus on three critical applications of PNPs in diseases: vascular disease therapy, cancer treatment, and management of infectious diseases. This review presents our knowledge of PNPs, summarizes their advancements in targeted therapies and discusses the promising potential for clinical translation of PNPs. [Display omitted] • Platelet membrane-coated nanoparticles (PNPs) combines platelet functions with nanomaterials for targeted drug delivery. • PNPs effectively manage vascular, cancer, and infectious diseases through precise targeting mechanisms. • Challenges such as optimizing safety and managing immune responses are critical for advancing PNPs to clinical use. [ABSTRACT FROM AUTHOR]

Deposits of crystals within the body, or exposure to external crystalline material, can cause diverse metabolic and inflammatory acute as well as chronic medical disorders. Neutrophils are crucial in the immune response to these pathogenic crystals, from contributing to necroinflammation and driving further tissue damage through the release of proinflammatory mediators and neutrophil extracellular trap (NET) formation to limiting inflammation. The mechanisms of how neutrophils respond to these pathogenic crystals, specifically their mode of cell death (e.g., NETosis, necrosis, necroptosis, and/or pyroptosis), depends on the crystal type, site of crystal deposition, and amount of crystals, all of which influence the intensity of inflammation. Targeting NET components and certain forms of neutrophil death as well as crystallization are novel treatment targets that may improve outcomes in crystal-associated disorders. Crystalline material can cause a multitude of acute and chronic inflammatory diseases, such as gouty arthritis, silicosis, kidney disease, and atherosclerosis. Crystals of various types are thought to cause similar inflammatory responses, including the release of proinflammatory mediators and formation of neutrophil extracellular traps (NETs), processes that further promote necroinflammation and tissue damage. It has become apparent that the intensity of inflammation and the related mechanisms of NET formation and neutrophil death in crystal-associated diseases can vary depending on the crystal type, amount, and site of deposition. This review details new mechanistic insights into crystal biology, highlights the differential effects of various crystals on neutrophils and extracellular trap (ET) formation, and discusses treatment strategies and potential future approaches for crystal-associated disorders. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a common cardiovascular disease in which the arteries are thickened due to buildup of plaque. This study aims to identify programmed cell death (PCD)-related biomarkers and explore the crucial regulatory mechanisms of atherosclerosis. Gene expression profiles of atherosclerosis and control groups from GSE20129 and GSE23746 were obtained. Necroptosis was elevated in atherosclerosis. Weighted gene co-expression network analysis (WGCNA) was conducted in GSE23746 and GSE56045 to identify PCD-related modules and to perform enrichment analysis. Two necroptosis-related genes (IRF9 and STAT1) were identified and considered as biomarkers. Enrichment analysis showed that these gene modules were mainly related to immune response regulation. In addition, single-cell RNA sequencing data from GSE159677 were obtained and the characteristic cell types of atherosclerosis were identified. A total of 11 immune cell types were identified through UMAP dimension reduction. Most immune cells were mainly enriched in plaque samples, and STAT1 and IRF9 were primarily expressed in T-cells and macrophages. Moreover, the roles of IRF9 and STAT1 were assessed and found to be significantly upregulated in atherosclerosis, which was associated with increased risk of atherosclerosis. This study provides a molecular feature of atherosclerosis, offering an important basis for further research on its pathological mechanisms and the search for new therapeutic targets. [ABSTRACT FROM AUTHOR]

Objective: It has been shown that clonal mutations occur in hematopoietic stem cells with advancing age and increase the risk of death due to atherosclerotic vascular diseases, similarly to myeloproliferative neoplasms. Endothelial cells (ECs) and hematopoietic stem cells develop from common stem cells called hemangioblasts in the early embryonic period. However, the presence of hemangioblasts in the postnatal period is controversial. In this study, JAK2 gene variants were examined in patients with atherosclerotic carotid disease and without any hematological malignancies. Materials and Methods: Ten consecutive patients (8 men and 2 women) with symptomatic atherosclerotic carotid stenosis were included in this study. ECs (CD31+CD45-) were separated from tissue samples taken by carotid endarterectomy. JAK2 variants were examined in ECs, peripheral blood mononuclear cells, and oral epithelial cells of the patients with next-generation sequencing. Results: The median age of the patients was 74 (range: 58-80) years and the median body mass index value was 24.44 (range: 18.42- 30.85) kg/m2. Smoking history was present in 50%, hypertension in 80%, diabetes in 70%, and ischemic heart disease in 70% of the cases. The JAK2V617F mutation was detected in the peripheral blood mononuclear cells of 3 of the 10 patients, and 2 patients also had the JAK2V617F mutation in their ECs. The JAK2V617F mutation was not found in the oral epithelial cells of any of the patients. Conclusion: In this study, for the first time in the literature, we showed that the JAK2V617F mutation was found somatically in both peripheral blood cells and ECs in patients with atherosclerosis. This finding may support that ECs and hematopoietic cells originate from a common clone or that somatic mutations can be transmitted to ECs by other mechanisms. Examining the molecular and functional changes caused by the JAK2V617F mutation in ECs may help open a new avenue for treating atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD. [ABSTRACT FROM AUTHOR]

Introduction: Coronary sclerosis is a risk factor for the progression to obstructive coronary artery disease (CAD). However, understanding its impact on the outcomes of patients with myocardial infarction and non-obstructive coronary arteries is limited. This study aimed to explore the prognostic influence of coronary sclerosis on in- and out-of-hospital events in troponin-positive patients with non-obstructive coronary arteries. Methods: This study was a retrospective cohort analysis based on prospectively collected data. A total of 24,775 patients who underwent coronary angiography from 2010 to 2021 in a German university hospital were screened, resulting in a final study cohort of 373 troponin-positive patients with non-obstructive coronary arteries and a follow-up period of 6.2 ± 3.1 years. Coronary sclerosis was defined as coronary plaques without angiographically detectable stenotic lesions of 50% or more in the large epicardial coronary arteries. The primary study endpoint was the occurrence of in-hospital events. Secondary endpoints included events during follow-up. Results: Patients with coronary sclerosis were significantly older (70 ± 12 vs. 58 ± 16 years, p < 0.001), had ST-segment elevation less frequently on electrocardiogram (9.4% vs. 18.7%, p = 0.013), and suffered more often from diabetes mellitus (23.3% vs. 13.1%, p = 0.009), arterial hypertension (79.6% vs. 59.8%, p < 0.001), chronic obstructive pulmonary disease (17.1% vs. 9.4%, p = 0.028), chronic kidney disease (22.2% vs. 8.4%, p < 0.001), atrial fibrillation (19.8% vs. 12.2%, p = 0.045), and valvular diseases than patients without CAD. Patients with coronary sclerosis were more likely to receive medication for primary/secondary prevention on admission and at discharge. The incidence of in- and out-of-hospital events was significantly higher in patients with coronary sclerosis (in-hospital: 42.8% vs. 29.9%, p = 0.010; out-of-hospital: 46.0% vs. 26.1%, p < 0.001). Mortality rates tended to be higher in the coronary sclerosis group (29.4% vs. 20.0%, p = 0.066). Conclusion: Patients diagnosed with coronary sclerosis presented a higher incidence of comorbidities and increased medication use, and experienced higher rates of both in-hospital and out-of-hospital events, primarily due to the clustering of cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota and its by‐products are increasingly recognized as having a decisive role in cardiovascular diseases. The aim is to study the relationship between gut microbiota and early vascular ageing (EVA). Methods: A cross‐sectional study was developed in Salamanca (Spain) in which 180 subjects aged 45–74 years were recruited. EVA was defined by the presence of at least one of the following: carotid‐femoral pulse wave velocity (cf‐PWV), cardio‐ankle vascular index (CAVI) or brachial‐ankle pulse wave velocity (ba‐PWV) above the 90th percentile of the reference population. All other cases were considered normal vascular ageing (NVA). Measurements: cf‐PWV was measured by SphygmoCor® System; CAVI and ba‐PWV were determined by Vasera 2000® device. Gut microbiome composition in faecal samples was determined by 16S rRNA Illumina sequencing. Results: Mean age was 64.4 ± 6.9 in EVA group and 60.4 ± 7.6 years in NVA (p <.01). Women in EVA group were 41% and 53% in NVA. There were no differences in the overall composition of gut microbiota between the two groups when evaluating Firmicutes/Bacteriodetes ratio, alfa diversity (Shannon Index) and beta diversity (Bray‐Curtis). Bilophila, Faecalibacterium sp.UBA1819 and Phocea, are increased in EVA group. While Cedecea, Lactococcus, Pseudomonas, Succiniclasticum and Dielma exist in lower abundance. In logistic regression analysis, Bilophila (OR: 1.71, 95% CI: 1.12–2.6, p =.013) remained significant. Conclusions: In the studied Spanish population, early vascular ageing is positively associated with gut microbiota abundance of the genus Bilophila. No relationship was found between phyla abundance and measures of diversity. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with an increased risk of coronary artery disease. Computed Tomography Coronary Angiography (CTCA) can assess both the extent and the features of coronary plaques. We aimed to gather evidence about the prevalence and features of coronary plaques among MASLD patients. Methods: PubMed, Scopus, and Google Scholar databases were searched for randomized controlled trials and adjusted observational studies assessing the prevalence and features of coronary plaques by means of CTCA in MASLD patients as compared with a control group. The prevalence of coronary stenosis (defined as >30% and >50% diameter of stenosis), of increasing coronary artery calcium (CAC) score and of high‐risk features (namely low‐attenuation plaques, napkin ring sign, spotty calcification and positive remodelling) in MASLD patients were the endpoints of interest. Results: Twenty‐four observational studies were included. MASLD was associated with an increased prevalence of critical coronary stenosis compared with controls (odds ratio [OR] 1.54, 95%CI 1.23–1.93). Increased values of CAC score were observed in MASLD patients (OR 1.35, 95%CI 1.02–1.78 and OR 2.26, 95%CI 1.57–3.23 for CAC score 0–100 and >100, respectively). An increased risk of 'high‐risk' coronary plaques was observed in MASLD patients (OR 2.13, 95%CI 1.42–3.19). As high‐risk features plaques, a higher prevalence of positive remodelling and spotty calcification characterize MASLD patients (OR 2.92, 95%CI 1.79–4.77 and OR 2.96, 95%CI 1.22–7.20). Conclusions: Patients with MASLD are at increased risk of developing critical coronary stenosis and coronary plaques characterized by high‐risk features as detected by CTCA. [ABSTRACT FROM AUTHOR]

This study was to investigate the therapeutic effect of Bacillus amyloliquefaciens (Ba) on atherosclerosis (AS). THP-1 monocyte was differentiated to THP-1 macrophage (THP-M) through phorbol 12-myristate 13-acetate. After pre-treatment by 108 cfu/ml Ba lasting 6 h, THP-M was induced with 100 mg/l ox-LDL lasting 48 h to form macrophage foam cell (THP-F). RT-qPCR and flow cytometry were employed to determine the polarization of THP-M and THP-F. ApoE−/− mice with high-fat and high-cholesterol diet were used for constructing an AS model to evaluate the effect of Ba on AS. Our in vitro results showed that Ba vegetative cells pre-treatment distinctly inhibited the levels of iNOS and CD16/CD32 (M1 macrophage markers), and increased the levels of FIZZ1, Ym1, Arg1, CD163, and CD206 (M2 macrophage markers), indicating that Ba pre-treatment promoted anti-inflammatory M2-like polarization both in THP-M and THP-F. Meanwhile, it also suppressed cholesterol uptake, esterification, and hydrolysis, and efflux by THP-M and THP-F. Additionally, our animal experiments demonstrated that Ba vegetative cells treatment suppressed high cholesterol, hyperglycemia, hyperlipidemia, and the release of inflammatory factors (TNF-α, IL-6 and IL-1β) in ApoE−/− AS mice. In a word, our results indicated that Ba may protect against AS through alleviating foam cell formation and macrophage polarization through targeting certain stages of AS. [ABSTRACT FROM AUTHOR]

• Low-level laser light suppresses oxidative stress and enhances antioxidant defenses. • Sargassum latifolium showed antiatherosclerotic effects in combination with low-level laser irradiation in rats. • The synergistic effect of each algal dry biomass concentration with low-level laser irradiation on rats. • Sargassum latifolium showed 74.8 % of FRAB scavenging power and, 76.08 % Cox1 inhibition. Atherosclerosis is considered the most common underlying cause of most cardiovascular diseases. Most conventional therapies focus on lipid levels but fail to reduce oxidative stress and inflammation. In contrast, seaweeds can solve such problems, with their antihypercholesterolemic properties. The current study aims to evaluate the antiatherosclerotic effects of the brown alga Sargassum latifolium and low-level laser irradiation in rats fed on a hypercholesterolemic diet, individually or in combination. Two doses of S. latifolium dry biomass (5 and 10 %) were orally gavaged to rats with and without low-level laser irradiation (650 nm laser 100 mW) compared with Atorvastatine Ca (Lipitor). The alga phytochemical contents were estimated with (GC–MS) analysis, evaluating its antioxidant, anti-inflammatory, and antihypercholesterolemic activities. S. latifolium showed 74.8 % of FRAP scavenging power and 76.08 % Cox1 inhibition. In addition to suppressing weight gain and blood viscosity in hypercholesterolemic rats, the algal laser treatment demonstrated a significant improvement in serum HDL-cholesterol and a reduction in serum total lipids, triglycerides, total cholesterol, LDL-cholesterol, and VLDL-cholesterol concentrations. Additionally, there was a significant improvement in serum HDL-cholesterol and a significant reduction in elevated atherogenic index, risk factor, inflammatory marker (CRP), creatine kinase, lactate dehydrogenase activities, and serum liver and kidney function biomarkers. The best results were achieved by treatment of hypercholesterolemic rats with a high dose of S. latifolium with laser irradiation. In conclusion, the synergistic effect of S. latifolium seaweed (especially high dose) and low-level laser has great potential, which exceeds that of anticholesterol drugs for preventing and/or therapy of hypercholesterolemia and maintaining overall health. Thus, this synergistic effect is a potential source of a new therapy that provides antihypercholesterolemic and antiatherosclerotic effects similar to, or better than, those of more traditional pharmaceutical drugs. [ABSTRACT FROM AUTHOR]

Summary: Retinopathy and albuminuria are associated with hip fracture risk. We investigated whether these disorders and endothelial dysfunction (which underlies microvascular diseases) were associated with low trabecular bone density. No significant associations were found, suggesting that microvascular diseases are not related to fracture risk through low trabecular bone density. Purpose: Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures. Methods: Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5 min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction. Results: We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results. Conclusion: We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Evidence has shown that microRNAs (miRNAs/ miRs) play key roles in biological functions of vascular smooth muscle cells (VSMCs). However, the role of miR-374a in VSMCs remains to be elucidated. The present study aimed to explore the influence of miR-374a on VSMCs and its molecular mechanism. The expression level of miR-374a was measured by reverse transcription-quantitative (RT-q) PCR. MTT and Transwell assay were employed to assess the role of miR-374a in proliferation and migration of VSMCs. To order to determine miR-374a targets, a dual-luciferase reporter assay was conducted, which was further verified by rescue experiments. Chromatin Immunoprecipitation Assay and JASPAR databases were applied to explore the regulatory association between GATA binding protein 2 (GATA2) and miR-374a. Western blotting or RT-qPCR were employed to detect the protein expression levels of GATA2 or RAR-related orphan receptor A (RORA). The present study found that miR-374a was elevated in VSMCs following treatment with platelet-derived growth factor-BB (PDGF-BB) compared with that in control group. In addition, the results demonstrated that a higher expression of a miR-374a could promote proliferation and migration of VSMCs while miR-374a inhibitor suppressed the PDGF-BB-induced proliferation and migration of VSMCs in vitro. Furthermore, circTADA2A bound to miR-374a and then upregulated RORA expression, which resulted in inhibition in VSMCs proliferation and migration. On the other hand, the result indicated that GATA2 overexpression could augment the proliferation, migration of PDGF-bb-induced VSMCs, which could be rescued by miR-374a inhibitor. The findings suggested that the GATA2/circTADA2A-miR-374a axis promoted the proliferation and migration of VSMCs by targeting RORA, which were closely related to atherosclerosis (AS). Thus the results might offer a new therapeutic target for AS. [ABSTRACT FROM AUTHOR]

Atherosclerosis is essentially the leading factor behind occurrences of cardiovascular diseases (CVDs)- associated incidents, while mitochondrial dysfunction is also the main cause of atherosclerosis. The present study conducted a comparative analysis of mitochondrial function-related indicators in cholesterol-induced vascular endothelial cells (VECs) from Mongolian gerbils, Sprague-Dawley (SD) rats and humans. It reported that the inhibitory effect of cholesterol treatment on the viability of Mongolian gerbil VECs was markedly lower than the other two types of VECs at the same concentration. Following cholesterol treatment, mitochondrial DNA copy numbers, reactive oxygen species level, calcium concentration and mitochondrial membrane potential of Mongolian gerbil VECs did not change markedly. These results suggested that the function of mitochondria in the VECs of Mongolian gerbil is normal. Additionally, cholesterol treatment also did not alter the levels of superoxide dismutase, glutathione peroxidase, ATP, NADH-CoQ reductase and cytochrome c oxidase in Mongolian gerbil VECs. It was hypothesized that the VECs of Mongolian gerbils have certain resistance to oxidative damage induced by cholesterol. In brief, the present study demonstrated that VECs of Mongolian gerbils are resistant to cholesterol-induced mitochondrial dysfunction and oxidative damage. The aforementioned findings establish a theoretical foundation for the advancement of innovative strategies in the prevention and treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Macrophages in atherosclerotic lesions exhibit a spectrum of behaviours or phenotypes. The phenotypic distribution of monocyte-derived macrophages (MDMs), its correlation with MDM lipid content, and relation to blood lipoprotein densities are not well understood. Of particular interest is the balance between low density lipoproteins (LDL) and high density lipoproteins (HDL), which carry bad and good cholesterol respectively. To address these issues, we have developed a mathematical model for early atherosclerosis in which the MDM population is structured by phenotype and lipid content. The model admits a simpler, closed subsystem whose analysis shows how lesion composition becomes more pathological as the blood density of LDL increases relative to the HDL capacity. We use asymptotic analysis to derive a power-law relationship between MDM phenotype and lipid content at steady-state. This relationship enables us to understand why, for example, lipid-laden MDMs have a more inflammatory phenotype than lipid-poor MDMs when blood LDL lipid density greatly exceeds HDL capacity. We show further that the MDM phenotype distribution always attains a local maximum, while the lipid content distribution may be unimodal, adopt a quasi-uniform profile or decrease monotonically. Pathological lesions exhibit a local maximum in both the phenotype and lipid content MDM distributions, with the maximum at an inflammatory phenotype and near the lipid content capacity respectively. These results illustrate how macrophage heterogeneity arises in early atherosclerosis and provide a framework for future model validation through comparison with single-cell RNA sequencing data. [ABSTRACT FROM AUTHOR]

Alterations in vascular extracellular matrix (ECM) components, interactions, and mechanical properties influence both the formation and stability of atherosclerotic plaques. This review discusses the contribution of the ECM microenvironment in vascular homeostasis and remodeling in atherosclerosis, highlighting Cartilage oligomeric matrix protein (COMP) and its degrading enzyme ADAMTS7 as examples, and proposes potential avenues for future research aimed at identifying novel therapeutic targets for atherosclerosis based on the ECM microenvironment. [ABSTRACT FROM AUTHOR]

Objectives: Current coronary CT angiography (CTA) guidelines suggest both end-systolic and mid-diastolic phases of the cardiac cycle can be used for CTA image acquisition. However, whether differences in the phase of the cardiac cycle influence coronary plaque measurements is not known. We aim to explore the potential impact of cardiac phases on quantitative plaque assessment. Methods: We enrolled 39 consecutive patients (23 male, age 66.2 ± 11.5 years) who underwent CTA with dual-source CT with visually evident coronary atherosclerosis and with good image quality. End-systolic and mid- to late-diastolic phase images were reconstructed from the same CTA scan. Quantitative plaque and stenosis were analyzed in both systolic and diastolic images using artificial intelligence (AI)–enabled plaque analysis software (Autoplaque). Results: Overall, 186 lesions from 39 patients were analyzed. There were excellent agreement and correlation between systolic and diastolic images for all plaque volume measurements (Lin's concordance coefficient ranging from 0.97 to 0.99; R ranging from 0.96 to 0.98). There were no substantial intrascan differences per patient between systolic and diastolic phases (p > 0.05 for all) for total (1017.1 ± 712.9 mm3 vs. 1014.7 ± 696.2 mm3), non-calcified (861.5 ± 553.7 mm3 vs. 856.5 ± 528.7 mm3), calcified (155.7 ± 229.3 mm3 vs. 158.2 ± 232.4 mm3), and low-density non-calcified plaque volume (151.4 ± 106.1 mm3 vs. 151.5 ± 101.5 mm3) and diameter stenosis (42.5 ± 18.4% vs 41.3 ± 15.1%). Conclusion: Excellent agreement and no substantial differences were observed in AI-enabled quantitative plaque measurements on CTA in systolic and diastolic images. Following further validation, standardized plaque measurements can be performed from CTA in systolic or diastolic cardiac phase. Clinical relevance statement: Quantitative plaque assessment using artificial intelligence–enabled plaque analysis software can provide standardized plaque quantification, regardless of cardiac phase. Key Points: • The impact of different cardiac phases on coronary plaque measurements is unknown. • Plaque analysis using artificial intelligence–enabled software on systolic and diastolic CT angiography images shows excellent agreement. • Quantitative coronary artery plaque assessment can be performed regardless of cardiac phase. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effects of low tube voltage on coronary plaques and pericoronary fat assessment, and to compare their extent among various levels of low voltage. Materials and methods: Patients were recommended for high-pitch low-tube voltage coronary computed tomography angiography (CCTA), and they were included if they had poor image quality and were referred to a conventional CCTA. The patients were classified into a low-voltage group (with 70-kV, 80-kV, and 90-kV subgroups) and a conventional group (100/120 kV). Their total plaque and subcomponent volumes and pericoronary fat attenuation index (FAI) were measured. Results: A total of 1002 image slices (from 65 patients and 74 plaques) were included, including 21, 31, 13, 4, and 61 patients in the 70-kV, 80-kV, 90-kV, 100-kV, and 120-kV groups respectively. The CT values of noncalcified plaques in the conventional and low-voltage groups were 54.6 ± 21.3 HU and 31.5 ± 22.6 HU, respectively (p < 0.05). Compared with the conventional group, the necrotic core and calcification volume were increased, and the fibrolipid volume, periplaque, and right coronary artery FAI were decreased in the low-voltage group and its subgroups (p < 0.001). The magnitude of changes in fibrous and calcification volumes increased in the 70-kV subgroup compared with that in the 90-kV subgroup (p < 0.05). Conclusion: Low tube voltages, particularly of 70 kV, have a significant effect on coronary plaque and FAI. The effect of low voltage on plaque composition is characterized by a polarization pattern, i.e., a decrease in fibrolipid (medium density) and an increase in necrotic core (low density) and calcification (high density). Clinical relevance statement: Our results highlight the comparability and repeatability of plaque and pericoronary fat assessments facilitated by the same or a similar tube voltage. It is necessary to carry out studies on the specificity threshold of low tube voltage at each level. Key Points: • Low tube voltage had a significant effect on coronary plaque and pericoronary fat, particularly 70 kV. • The effect of low tube voltage on plaque composition shows the shift from medium-density mixed components to low- and high-density components. • It is necessary to correct the specificity threshold or attenuation difference for low tube voltage at each level. [ABSTRACT FROM AUTHOR]

Background: Macrophage-mediated cleaning up of dead cells is a crucial determinant in reducing coronary artery inflammation and maintaining vascular homeostasis. However, this process also leads to programmed death of macrophages. So far, the role of macrophage death in the progression of atherosclerosis remains controversial. Also, the underlying mechanism by which transcriptional regulation and reprogramming triggered by macrophage death pathways lead to changes in vascular inflammation and remodeling are still largely unknown. TRIM25-mediated RIG-I signaling plays a key role in regulation of macrophages fate, however the role of TRIM25 in macrophage death-mediated atherosclerotic progression remains unclear. This study aims to investigate the relationship between TRIM25 and macrophage death in atherosclerosis. Methods: A total of 34 blood samples of patients with coronary stent implantation, including chronic total occlusion (CTO) leisions (n = 14) or with more than 50% stenosis of a coronary artery but without CTO leisions (n = 20), were collected, and the serum level of TRIM25 was detected by ELISA. Apoe−/− mice with or without TRIM25 gene deletion were fed with the high-fat diet (HFD) for 12 weeks and the plaque areas, necrotic core size, aortic fibrosis and inflammation were investigated. TRIM25 wild-type and deficient macrophages were isolated, cultured and stimulated with ox-LDL, RNA-seq, real-time PCR, western blot and FACS experiments were used to screen and validate signaling pathways caused by TRIM25 deletion. Results: Downregulation of TRIM25 was observed in circulating blood of CTO patients and also in HFD-induced mouse aortas. After HFD for 12 weeks, TRIM25−/−ApoeE−/− mice developed smaller atherosclerotic plaques, less inflammation, lower collagen content and aortic fibrosis compared with TRIM25+/+ApoeE−/− mice. By RNA-seq and KEGG enrichment analysis, we revealed that deletion of TRIM25 mainly affected pyroptosis and necroptosis pathways in ox-LDL-induced macrophages, and the expressions of PARP1 and RIPK3, were significantly decreased in TRIM25 deficient macrophages. Overexpression of TRIM25 promoted M1 polarization and necroptosis of macrophages, while inhibition of PARP1 reversed this process. Further, we observed that XRCC1, a repairer of DNA damage, was significantly upregulated in TRIM25 deficient macrophages, inhibiting PARP1 activity and PARP1-mediated pro-inflammatory change, M1 polarization and necroptosis of macrophages. By contrast, TRIM25 overexpression mediated ubiquitination of XRCC1, and the inhibition of XRCC1 released PARP1, and activated macrophage M1 polarization and necroptosis, which accelerated aortic inflammation and atherosclerotic plaque progression. Conclusions: Our study has uncovered a crucial role of the TRIM25-XRCC1Ub-PARP1-RIPK3 axis in regulating macrophage death during atherosclerosis, and we highlight the potential therapeutic significance of macrophage reprogramming regulation in preventing the development of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis (AS) is the pathological basis of acute myocardial infarction, acute stroke, and other acute critical illnesses. Vascular smooth muscle cell (VSMC) phenotypic transformation plays a remarkable role in the occurrence and development of AS. Previous studies have found that GSK3β-TCF21 is a key signaling pathway regulating VSMC phenotypic transformation. Baicalin is an important herbal monomer for cardiovascular protection, but whether it can regulate the GSK3β-TCF21 signaling pathway and VSMC phenotypic transformation remains unclear. Purpose: The study aimed to explore the role of Baicalin in AS and VSMC phenotypic transformation and whether the GSK3β-TCF21 signaling pathway participates in this process. Materials and Methods: In this study, through the AS mouse model and ox-LDL-induced VSMC phenotypic transformation model in vitro, the effect of Baicalin on the GSK3β-TCF21 signaling pathway and VSMC phenotypic transformation was investigated. Results: Pathological staining showed that the AS plaque area of the Baicalin group decreased significantly (p < 0.001). The expression of the marker gene (TAGLN, ACTA2, CNN1, and MYH11) of VSMC phenotypic transformation was significantly increased (p < 0.001) after Baicalin treatment. Baicalin could activate GSK3β and increase the expression of TCF21 significantly (p < 0.001) to inhibit VSMC phenotypic transition. Inhibiting the GSK3β-TCF21 signaling pathway was able to reduce the effects of Baicalin on reducing VSMC phenotypic transition and protecting AS. Conclusion: Our study indicates that Baicalin is protective in inhibiting VSMC phenotypic transformation and ameliorating AS by regulating GSK3β-TCF21. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction (ED) is defined as an impairment in the vasodilatory, anti-thrombotic, and anti-inflammatory properties of the cells that make up the lining of blood vessels. ED is considered a key step in the development of atherosclerotic cardiovascular disease. The association between ED and systemic inflammatory diseases is well established. However, the prevalence and clinical significance of ED in psoriatic arthritis (PsA) have been investigated to a lesser extent. This review aims to explore the link between ED and PsA, including ED in macro- and microcirculation, as well as risk factors for its occurrence in PsA and its relationship with atherosclerosis in PsA. Furthermore, the ED in PsA was compared with that of rheumatoid arthritis (RA). Regarding ED in the microcirculation, the coronary flow reserve was found to be significantly reduced in individuals with PsA. The relationship between PsA and macrovascular ED is more pronounced, along with more advanced atherosclerosis detected in patients with PsA. These results are consistent with those obtained in RA studies. On the other hand, arterial stiffness and signs of vascular remodeling were found more frequently in RA than in PsA, with the potential role of efficient anti-TNF treatment in patients with PsA and psoriasis explaining this finding. The impact of ED on cardiovascular diseases and the burden of this risk caused independently by PsA have not yet been precisely established, however, this group of patients requires special attention with regard to cardiovascular events. [ABSTRACT FROM AUTHOR]

[Display omitted] • ASIC1 facilitates atherosclerosis via impeding lipophagy. • ASIC1 promotes RIP1 phosphorylation. • ASIC1-RIP1 interaction contributes to defective autophagy flux. • ASIC1/RIP1 facilitates lipid accumulation via inhibiting lipophagy. • ASIC1/RIP1 may be a novel target for atherosclerotic treatment. Atherosclerosis, a major contributor to cardiovascular disease, remains a significant health concern worldwide. While previous research has shown that acid-sensing ion channel 1 (ASIC1) impedes macrophage cholesterol efflux, its precise role in atherogenesis and the underlying mechanisms have remained elusive. This study aimed to investigate the role of ASIC1 in atherosclerosis and its underlying mechanisms. First, data from a single-cell RNA sequencing (scRNA-seq) database were used to explore the relationships between ASIC1 differential expression and lipophagy in human atherosclerotic lesions. Finally, we validated the role of ASIC1/RIP1 signaling in lipophagy in vivo (human and mice) and in vitro (RAW264.7 and HTP-1 cells). Our results demonstrated a significant increase in ASIC1 protein levels within CD68+ macrophages in both human aortic lesions and AopE-/- mouse lesion areas compared to nonlesion regions. Concurrently, there was a notable decrease in lipophagy, a crucial process for lipid metabolism. In vitro assays further elucidated that ASIC1 interaction with RIP1 (receptor-interacting protein 1) promoted the phosphorylation of RIP1 at serine 166 and transcription factor EB (TFEB) at serine 142, leading to disrupted lipophagy and increased lipid accumulation. Intriguingly, all these events were reversed upon ASIC1 deficiency and RIP1 inhibition. Furthermore, in ApoE-/- mouse models of atherosclerosis, silencing ASIC1 expression or inhibiting RIP1 activation not only significantly attenuated atherogenesis but also restored TFEB-mediated lipophagy in aortic tissues. This was evidenced by reduced TFEB Ser-142 phosphorylation, decreased LC3II and LAMP1 protein expression, increased numbers of lipophagosomes, and a decrease in lipid droplets. Our findings unveil the critical role of macrophage ASIC1 in interacting with RIP1 to inhibit lipophagy, thereby promoting atherogenesis. Targeting ASIC1 represents a promising therapeutic avenue for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • A hamster model lacking both LCAT and LDL receptor (DKO) was successfully constructed in the present study. • A significant reduction in plasma LDL-C and HDL-C levels with increased triglyceride and free cholesterol levels was observed in DKO hamsters on a regular chow diet. • Dyslipidemia contributed to HFD-induced atherosclerosis and fatty liver independent on LDL levels in DKO hamsters. • Lipid metabolism was impaired in primary peritoneal macrophages from DKO hamsters. Lecithin cholesterol acyltransferase (LCAT) plays a crucial role in acyl-esterifying cholesterol in plasma, which is essential for reverse cholesterol transport (RCT). Previous studies indicated that its activity on both α and β lipoproteins interpret its effects on lipoproteins for many controversial investigations of atherosclerosis. To better understand the relationship between LCAT, diet-induced dyslipidemia and atherosclerosis, we developed a double knockout (LCAT−/−&LDLR−/−, DKO) hamster model to evaluate the specific role of LCAT independent of LDL clearance effects. Plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and free cholesterol (FC) levels were measured using biochemical reagent kits. FPLC was performed to analyze the components of lipoproteins. Apolipoprotein content was assessed using western blotting (WB). The hamsters were fed a high cholesterol/high fat diet (HCHFD) to induce atherosclerosis. Oil Red O staining was employed to detect plaque formation. Peritoneal macrophages were studied to investigate the effects of LCAT on cholesterol uptake and efflux. On HCHFD, DKO hamsters exhibited significantly elevated levels of TG and FC, while HDL-C was nearly undetectable without affecting TC levels, as compared to low-density lipoprotein receptor (LDLR)-deficient (LDLR−/−, LKO) hamsters. Lipoprotein profiling revealed a marked increase in plasma chylomicron/very low-density lipoprotein (CM/VLDL) fractions, along with an unexpected reduction in LDL fraction in DKO hamsters. Furthermore, DKO hamsters displayed aggravated atherosclerotic lesions in the aorta, aortic root, and coronary artery relative to LKO hamsters, attributed to a pro-atherogenic lipoprotein profile and impaired cholesterol efflux in macrophages. Our study demonstrates the beneficial role of LCAT in inhibiting atherosclerotic development and highlights the distinctive lipid metabolism characteristics in hamsters with familial hypercholesterolemia. [ABSTRACT FROM AUTHOR]

The metabolism of choline (highly present in animal products) can produce trimethylamine N-oxide (TMAO), a metabolite with atherosclerotic effects; however, dietary fiber may suppress this metabolic pathway. This study aimed to develop a dietary pattern predictive of plasma TMAO and choline concentrations using reduced rank regression (RRR) and to evaluate its construct validity. Diet and plasma concentrations of choline (μmol/L) and TMAO (μmol/L) were assessed in 1724 post-menopausal women who participated in an ancillary study within the Women's Health Initiative Observational Study (1993–1998). The TMAO dietary pattern was developed using RRR in half of the sample (Training Sample) and applied to the other half of the sample (Validation Sample) to evaluate its construct validity. Energy-adjusted food groups were the predictor variables and plasma choline and TMAO, the response variables. ANCOVA and linear regression models were used to assess associations between each biomarker and the dietary pattern score. Discretionary fat, potatoes, red meat, and eggs were positively associated with the dietary pattern, while yogurt, fruits, added sugar, and starchy vegetables were inversely associated. Mean TMAO and choline concentrations significantly increased across increasing quartiles of the dietary pattern in the Training and Validation samples. Positive associations between the biomarkers and the TMAO dietary pattern were also observed in linear regression models (Validation Sample: TMAO, adjusted beta-coefficient = 0.037 (p-value = 0.0088); Choline, adjusted beta-coefficient = 0.011 (p-value = 0.0224). We established the TMAO dietary pattern, a dietary pattern reflecting the potential of the diet to contribute to plasma concentrations of TMAO and choline. • A diet pattern was created in post-menopausal women to predict plasma biomarkers. • The biomarkers used for development were trimethylamine N-oxide and choline. • The diet pattern consists of high intake of fat, red meat, and eggs. • The diet pattern consists of low intake of yogurt, fruit, and starchy vegetables. • The construct validity of this proposed atherogenic diet pattern was demonstrated. [ABSTRACT FROM AUTHOR]

Introduction: The objective of our study was to examine the clinical characteristics and underlying risk factors of acute ischemic stroke in patients aged 18–45. Materials and Methods: We prospectively studied etiology of patients aged 18–45 with acute ischemic stroke presenting to our hospital from September to December of the following year. We aimed for 80% statistical power at a 5% significance level with a precision of 0.15, which led us to a calculated sample size of 39. Results: Fifty patients were observed. The main risk factors identified were alcohol use (36%), smoking (30%), and hypertension (22%). Prothrombotic states were found to be a significant risk factor in cases where the stroke's origin was undetermined. The most common stroke subtype was large-artery atherosclerosis, which was followed by strokes with other underlying causes. There was a statistically significant association between hypertension and ischemic stroke subtypes (P = 0.01). Hypertension was associated with small-vessel disease (92.3%) and strokes with undetermined causes (56.5%), with P = 0.023 and P <0.001, respectively. Conclusions: Hypertension was associated with multiple stroke subtypes in young individuals. Therefore, it is essential to strictly control hypertension through antihypertensive therapy and lifestyle changes. As alcohol use and smoking are becoming more prevalent among young individuals, early implementation of awareness programs targeting primary stroke prevention is highly desirable. [ABSTRACT FROM AUTHOR]

Rapid changes in artificial intelligence (AI) have already impacted the medical field. While the use of AI to assist medical diagnosis has been documented, AI is continually expanding within medical applications. AI applications in sonography and their effect on ultrasound examinations and sonographers are still indeterminate. Six papers were reviewed to investigate AI applications and effects within the sonography field. These papers provided results on a range of ultrasound applications including breast, obstetric, skin lesions, carotid, blood flow and cardiac ultrasound imaging when combined with AI. In this narrative review, the application of AI demonstrated that accuracy and speed of clinical diagnosis can be improved. These six aspects of ultrasound imaging combined with AI demonstrated the potential to assist the operator and clinicians with a diagnosis in various applications and settings. Additionally, AI can be beneficial to telehealth applications for rural and remote areas where healthcare access can be limited. These changes are opportunities to assist with medical care to provide benefits to patients, sonographers and clinicians as AI transitions to a positive integration within many aspects of clinical care. [ABSTRACT FROM AUTHOR]

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Background: Blood flow signals may be a confounder in quantifying T1 values of plaque or thrombus and how to realize black‐blood T1 mapping remains a challenge task. Purpose: To develop a fast and three‐dimensional black‐blood T1 mapping technique for quantitative assessment of atherosclerosis and venous thrombosis. Study Type: Sequence development and optimization via phantoms and volunteers as well as pilot prospective. Phantom and Subjects: Numerical simulations, a standard phantom, 8 healthy volunteers (mean age, 22 ± 1 years; 5 males), and 19 patients (mean age, 57 ± 14 years; 13 males) with atherosclerosis or venous thrombosis. Field Strength/Sequence: 3T/inversion recovery spin‐echo sequence (IR‐SE), magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE), and black‐blood prepared MP2RAGE (BB‐MP2RAGE). Assessment: The black‐blood preparation (i.e., delay alternating with nutation for tailored excitation, DANTE) was incorporated into MP2RAGE for black‐blood T1 mapping. The BB‐MP2RAGE was optimized numerically based on the Bloch equation, and then the phantom study was performed to verify the accuracy of T1 mapping by BB‐MP2RAGE against IR‐SE and MP2RAGE. Preliminary clinical validation was prospectively performed to assess the flow suppression effect and its potential application in plaque and thrombosis identification. Statistical Tests: Pearson correlation test, Bland–Altman analysis, paired t‐test, and intraclass correlation coefficient. A P value <0.05 indicates a statistically significant difference. Results: Phantom experiments showed comparable accuracy of T1 maps by BB‐MP2RAGE with IR‐SE and MP2RAGE (all r2 > 0.99); Compared to MP2RAGE, BB‐MP2RAGE effectively nulled the blood flow signals, and had a significant improvement in contrast‐to‐noise ratio between static tissue and blood (250.5 ± 66.6 vs. 91.9 ± 35.9). BB‐MP2RAGE can quantify plaque or thrombus T1 relaxation time with blood flow signal suppression. Data Conclusion: Accurate T1 mapping with sufficient blood flow suppression was achieved by BB‐MP2RAGE. BB‐MP2RAGE has the potential to quantitatively characterize atherosclerosis and venous thrombosis. Level of Evidence: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Purpose of review: This review seeks to provide important information on each of the major domains of social determinants of health (SDOH) in the context of atherosclerotic cardiovascular disease. Recent findings: SDOH can be classified into five domains: social and community context, health care access and quality, neighborhood and built environment, economic stability, and education access and quality. SDOH are major drivers for cardiovascular health outcomes that exceed the impact from traditional risk factors, and explain inequities in health outcomes observed across different groups of individuals. Summary: SDOH profoundly impacts healthcare's receipt, delivery, and outcomes. Many patients fall within various disenfranchised groups (e.g., identify with minority race, low socioeconomic status, low educational attainment, LGBTQ+), which impact overall health status and care. Learning to understand, recognize, and address SDOH as the driving force of disparities are critical for achieving health equity in the prevention and adequate treatment of ASCVD. [ABSTRACT FROM AUTHOR]