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The editorial delves into the process of extracellular calcification in the human body, emphasizing its significance in skeletal development, defense against infections, and repair of damaged arteries. It presents a bell-shaped curve distribution of calcification strength in the population, indicating that a robust calcification process may be linked to improved survival and infection defense. The text also explores the impact of calcification on bone density, osteoporosis, osteoarthritis, and cardiovascular diseases, underscoring the importance of studying this process for a holistic understanding of health and disease. The authors advocate for further research in various fields to enhance knowledge on calcification and its implications on human health. [Extracted from the article]

Background/Objectives: Cerebrovascular events, such as strokes, are often preceded by the rupture of atherosclerotic plaques in the carotid arteries. This work introduces a novel approach to predict the occurrence of such events by integrating computational fluid dynamics (CFD), structural analysis, and machine learning (ML) techniques. The objective is to develop a predictive model that combines both imaging and non-imaging data to assess the risk of carotid atherosclerosis and subsequent cerebrovascular events, ultimately improving clinical decision-making. Methods: A multidisciplinary approach was employed, utilizing 3D reconstruction techniques and blood-flow simulations to extract key plaque characteristics. These were combined with patient-specific clinical data for risk evaluation. The study involved 134 asymptomatic individuals diagnosed with carotid artery disease. Data imbalance was addressed using two distinct approaches, with the optimal method chosen for training a Gradient Boosting Tree (GBT) classifier. The model's performance was evaluated in terms of accuracy, sensitivity, specificity, and ROC AUC. Results: The best-performing GBT model achieved a balanced accuracy of 88%, with a ROC AUC of 0.92, a sensitivity of 0.88, and a specificity of 0.91. This demonstrates the model's high predictive power in identifying patients at risk for cerebrovascular events. Conclusions: The proposed method effectively combines CFD, structural analysis, and ML to predict cerebrovascular event risk in patients with carotid artery disease. By providing clinicians with a tool for better risk assessment, this approach has the potential to significantly enhance clinical decision-making and patient outcomes. [ABSTRACT FROM AUTHOR]

The inhibitor-kappaB kinase epsilon (IKKε) represents a non-canonical IκB kinase that modulates NF-κB activity and interferon I responses. Inhibition of this pathway has been linked with atherosclerosis and metabolic dysfunction-associated steatotic liver disease (MASLD), yet the results are contradictory. In this study, we employed a combined model of hepatic PCSK9D377Y overexpression and a high-fat diet for 16 weeks to induce atherosclerosis and liver steatosis. The development of atherosclerotic plaques, serum lipid concentrations, and lipid metabolism in the liver and adipose tissue were compared between wild-type and IKKε knock-out mice. The formation and progression of plaques were markedly reduced in IKKε knockout mice, accompanied by reduced serum cholesterol levels, fat deposition, and macrophage infiltration within the plaque. Additionally, the development of a fatty liver was diminished in these mice, which may be attributed to decreased levels of multiple lipid species, particularly monounsaturated fatty acids, triglycerides, and ceramides in the serum. The modulation of several proteins within the liver and adipose tissue suggests that de novo lipogenesis and the inflammatory response are suppressed as a consequence of IKKε inhibition. In conclusion, our data suggest that the knockout of IKKε is involved in mechanisms of both atherosclerosis and MASLD. Inhibition of this pathway may therefore represent a novel approach to the treatment of cardiovascular and metabolic diseases. [ABSTRACT FROM AUTHOR]

Patients with unstable angina present clinical characteristics of atherosclerotic plaque vulnerability, contrary to chronic coronary syndrome patients. The process of athersclerotic plaque destabilization is also regulated by microRNA particles. In this study, the investigation on expression levels of microRNAs inhibiting the expression of proteins that protect from atherosclerotic plaque progression (miR-92a inhibiting KLF2, miR-10b inhibiting KLF4, miR-126 inhibiting MerTK, miR-98 inhibiting IL-10, miR-29b inhibiting TGFβ1) was undertaken. A number of 62 individuals were enrolled—unstable angina (UA, n = 14), chronic coronary syndrome (CCS, n = 38), and healthy volunteers (HV, n = 10). Plasma samples were taken, and microRNAs expression levels were assessed by qRT-PCR. As a result, the UA patients presented significantly increased miR-10b levels compared to CCS patients (0.097 vs. 0.058, p = 0.033). Moreover, in additional analysis when UA patients were grouped together with stable patients with significant plaque in left main or proximal left anterior descending ("UA and LM/proxLAD" group, n = 29 patients) and compared to CCS patients with atherosclerotic lesions in other regions of coronary circulation ("CCS other" group, n = 25 patients) the expression levels of both miR-10b (0.104 vs. 0.046; p = 0.0032) and miR-92a (92.64 vs. 54.74; p = 0.0129) were significantly elevated. In conclusion, the study revealed significantly increased expression levels of miR-10b and miR-92a, a regulator of endothelial protective KLF factors (KLF4 and KLF2, respectively) in patients with more vulnerable plaque phenotypes. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a term derived from the Greek "athero" (atheroma) and "sclerosis" (hardening), is a long-standing process that leads to the formation of atheromatous plaques in the arterial wall, contributing to the development of atherosclerotic cardiovascular disease. The proliferation and migration of vascular smooth muscle cells (VSMCs) and the switching of their phenotype play a crucial role in the whole process. Retinoic acid (RA), a natural derivative of vitamin A, has been used in the treatment of various inflammatory diseases and cell proliferation disorders. Numerous studies have demonstrated that RA has an important inhibitory effect on the proliferation, migration, and dedifferentiation of vascular smooth muscle cells, leading to a significant reduction in atherosclerotic lesions. In this review article, we explore the effects of RA on the pathogenesis of atherosclerosis, focusing on its regulatory action in VSMCs and its role in the phenotypic switching, proliferation, and migration of VSMCs. Despite the potential impact that RA may have on the process of atherosclerosis, further studies are required to examine its safety and efficacy in clinical practice. [ABSTRACT FROM AUTHOR]

Background. Oxidative stress and inflammation are typically implied in atherosclerosis pathogenesis and progression, especially in coronary artery disease (CAD). Our objective was to investigate the oxidative stress and inflammation burden directly associated with atherosclerotic plaque in patients with stable coronary disease undergoing coronary artery bypass graft (CABG) surgery. Specifically, markers of oxidative stress and inflammation were compared in blood samples obtained from the atherosclerotic left anterior descending artery (LAD) and blood samples obtained from the healthy left internal thoracic artery (LITA), used as a bypass graft, within the same patient. Methods. Twenty patients scheduled for off-pump CABG were enrolled. Blood samples were collected from the LITA below anastomosis and the LAD below the stenosis. Samples were analysed for oxidative stress (sNOXdp, H2O2, NO) and inflammation markers (TNFα, IL-6, IL-1β, IL-10). Results. The analysis showed a significant increase in oxidative stress burden in the LAD as compared to LITA, as indicated by higher sNOX2-dp and H2O2 levels and lower NO levels (p < 0.01). Also, pro-inflammatory cytokines were increased in the LAD as compared to the LITA, as indicated by higher TNFα and IL-6 amounts (p < 0.01). On the other hand, no significant differences could be seen regarding IL-1β and IL-10 levels between the two groups. Conclusions. The oxidative stress and inflammatory burden are specifically enhanced in the LAD artery of stable coronary patients compared to systemic blood from the LITA of stable coronary patients. [ABSTRACT FROM AUTHOR]

Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels, with limited preventive and treatment options currently available. In this study, a vaccine prepared with COL6A6 peptide (named the Pep_A6 vaccine) was administered to immunize Apoe−/− mice, and the immune mechanism of the Pep_A6 vaccine against atherosclerosis was first investigated. The results of arterial oil red O staining demonstrated that the Pep_A6 vaccine significantly reduced the atherosclerotic plaque area in Apoe−/− mice fed with a high-fat diet for 20 weeks. A flow cytometry analysis revealed that the Pep_A6 vaccine inhibited Th1 cell differentiation and increased the proportion of Treg cells. Furthermore, there was a significant increase in Ly6Clow monocytes observed in the vaccinated group. The ELISA results showed that the Pep_A6 vaccine induced a significant expression of Pep_A6-specific antibody IgG and IgG1 in mouse serum. Additionally, we found that the Pep_A6 vaccine significantly decreased serum LDL-C content and regulated the expression of genes related to liver lipid metabolism. Together, our findings suggest that the Pep_A6 vaccine alleviates atherosclerosis by inducing a positive immune response and regulating lipid metabolism, providing new insights into potential prevention strategies for atherosclerosis as an innovative vaccine. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with increased cardiovascular disease (CVD) risk and mortality. This work aimed to evaluate the serum levels of the novel CV biomarkers fetuin-A (fet-A), Dickkopf-1 (DKK-1), galectin-3 (Gal-3), interleukin-32 (IL-32), and catestatin (CST) in RA patients and their associations with RA parameters and CVD markers. A cohort of 199 RA patients was assessed for traditional CVD risk factors, RA disease activity, and biomarker levels. Carotid ultrasound was used to measure carotid intima-media thickness (cIMT) and carotid plaque presence (cPP). Multivariate analyses examined correlations between biomarkers and RA parameters, serological markers, and CVD markers. Adjusted models showed that elevated CST expression levels were associated with rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity (OR = 2.45, p = 0.0001 and OR = 1.48, p = 0.04, respectively) in the overall cohort and for RF in men and women, respectively. In addition, fet-A concentration was inversely associated with the erythrocyte sedimentation rate (ESR) in the overall cohort (β = −0.15, p = 0.038) and in women (β = −0.25, p = 0.004). Fet-A levels were also negatively correlated with disease activity (DAS28-ESR) scores (β = −0.29, p = 0.01) and fibrinogen concentration (β = −0.22, p = 0.01) in women. No adjusted associations were observed for Gal-3, DKK-1 or IL32 concentration. The study revealed no significant associations between the biomarkers and cIMT or cPP. The measurement of CST and fet-A levels could enhance RA patient management and prognosis. However, the utility of biomarkers for evaluating CV risk via traditional surrogate markers is limited, highlighting the need for continued investigations into their roles in RA. [ABSTRACT FROM AUTHOR]

Atherosclerosis involves an inflammatory response due to plaque formation within the arteries, which can lead to ischemic stroke and heart disease. It is one of the leading causes of death worldwide, with various contributing factors such as hyperlipidemia, hypertension, obesity, diabetes, and smoking. Wall shear stress (WSS) is also known as a contributing factor of the formation of atherosclerotic plaques. Since the causes of atherosclerosis cannot be attributed to a single factor, clearly understanding the mechanisms and causes of its occurrence is crucial for preventing the disease and developing effective treatment strategies. To better understand atherosclerosis and define the correlation between various contributing factors, computational fluid dynamics (CFD) analysis is primarily used. CFD simulates WSS, the frictional force caused by blood flow on the vessel wall with various hemodynamic changes. Using apolipoprotein E knockout (ApoE-KO) mice subjected to partial ligation and a high-fat diet at 1-week, 2-week, and 4-week intervals as an atherosclerosis model, CFD analysis was conducted along with the reconstruction of carotid artery blood flow via magnetic resonance imaging (MRI) and compared to the inflammatory factors and pathological staining. In this experiment, a comparative analysis of the effects of high WSS and low WSS was conducted by comparing the standard deviation of time-averaged wall shear stress (TAWSS) at each point within the vessel wall. As a novel approach, the standard deviation of TAWSS within the vessel was analyzed with the staining results and pathological features. Since the onset of atherosclerosis cannot be explained by a single factor, the aim was to find the correlation between the thickness of atherosclerotic plaques and inflammatory factors through standard deviation analysis. As a result, the gap between low WSS and high WSS widened as the interval between weeks in the atherosclerosis mouse model increased. This finding not only linked the occurrence of atherosclerosis to WSS differences but also provided a connection to the causes of vulnerable plaques. [ABSTRACT FROM AUTHOR]

Atherosclerosis, marked by plaque accumulation within arteries, results from lipid dysregulation, inflammation, and vascular remodeling. Plaque composition, including lipid-rich cores and fibrous caps, determines stability and vulnerability. Photodynamic therapy (PDT) has emerged as a promising treatment, leveraging photosensitizers to induce localized cytotoxicity upon light activation. PDT targets plaque components selectively, reducing burden and inflammation. Challenges remain in optimizing PDT parameters and translating preclinical success to clinical efficacy. Nonetheless, PDT offers a minimally invasive strategy for atherosclerosis management, promising personalized interventions for cardiovascular health. The objective of the current study was to present the findings from quantitative non-contrast MRI of atherosclerosis post-PDT by assessing relaxation times. The study aimed to utilize and optimize a 1.5T MRI system. Clinical scanners were used for MRI examinations. The research involved analyzing T1 and T2 relaxation times. Following treatment of the samples with Rose Bengal and exposure to pure oxygen, PDT irradiation was administered. The results indicated that the therapy impacted the crus, evidenced by a significant decrease in relaxation times in the MRI data. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5–67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is the leading global cause of mortality, accounting for approximately 30% of all deaths. It is primarily characterized by the accumulation of atherosclerotic plaques within the coronary arteries, leading to reduced blood flow to the heart muscle. Early detection of atherosclerotic plaques is crucial to prevent major adverse cardiac events. Notably, recent studies have shown that 15% of myocardial infarctions occur in patients with non-obstructive CAD, underscoring the importance of comprehensive plaque assessment beyond merely identifying obstructive lesions. Cardiac Computed Tomography Angiography (CCTA) has emerged as a cost-effective and efficient technique for excluding obstructive CAD, particularly in patients with a low-to-intermediate clinical likelihood of the disease. Recent advancements in CCTA technology, such as improved resolution and reduced scan times, have mitigated many technical challenges, allowing for precise quantification and characterization of both calcified and non-calcified atherosclerotic plaques. This review focuses on two critical physiological aspects of atherosclerotic plaques: the burden of calcifications, assessed via the coronary artery calcium score (CACs), and perivascular fat attenuation index (pFAI), an emerging marker of vascular inflammation. The CACs, obtained through non-contrast CT scans, quantifies calcified plaque burden and is widely used to stratify cardiovascular risk, particularly in asymptomatic patients. Despite its prognostic value, the CACs does not provide information on non-calcified plaques or inflammatory status. In contrast, the pFAI, derived from CCTA, serves as an indirect marker of coronary inflammation and has shown potential in predicting adverse cardiac events. Combining both CACs and pFAI assessment could offer a comprehensive risk stratification approach, integrating the established calcification burden with novel inflammatory markers to enhance CAD prevention and management strategies. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) intensity could play a key role in atherosclerosis risk, but the existing literature shows controversial results. The aim of this study was to analyze the association of different PA levels with the presence of subclinical atherosclerosis in femoral and carotid arteries. Methods: A cross-sectional analysis was conducted of 449 middle-aged men belonging to the Aragon Workers' Health Study. Demographic, anthropometric, and clinical data were obtained during the annual medical examination. Ultrasonography was used to assess the presence of atheroma plaques in femoral and carotid territories. Accelerometry was used to assess habitual PA. Participants were categorized into vigorous PA (VPA) groups (0 min/week, >0–60 min/week, >60 min/week), and into moderate to vigorous PA (MVPA) groups using terciles as cut-offs. Results: Compared with participants who completed 0 min/week of VPA, those participants who completed >60 min/week of VPA had fully adjusted odds of subclinical atherosclerosis of 0.47 (95%CI: 0.22, 0.99, p < 0.05) and 0.35 (95%CI: 0.17, 0.73, p < 0.05) for femoral and any territory (femoral and/or carotid) respectively. No significant differences were observed in the prevalence of atheroma plaques in any vascular territory between the different MVPA groups. Conclusions: Performing more than 60 min/week of VPA is associated with reduced odds for subclinical atherosclerosis in femoral or any vascular territory in adult men. [ABSTRACT FROM AUTHOR]

Lipid lowering, with the use of statins after an acute coronary syndrome (ACS), is a cornerstone, well-established strategy for the secondary prevention of ischemic events in this high-risk cohort. In addition to the positive effect on lipid levels, statins have also been linked to improved atherosclerotic plaque characteristics, such as plaque regression and inflammation reduction, associated with the extent of reduction in LDL-C. The recent emergence of PCSK9 inhibitors for the management of dyslipidemia and the more extensive lipid lowering provided by these agents may provide better prevention for ACS patients when initiated after the ACS event. Several trials have evaluated the immediate post-ACS initiation of PCSK9 inhibitors, which has shown, to date, beneficial results. Furthermore, PCSK9 inhibitors have been linked with positive plaque remodeling and associated mortality benefits, which makes their use in the initial management strategy of such patients appealing. Therefore, in this review, we will analyze the rationale behind immediate lipid lowering after an ACS, report the evidence of PCSK9 inhibition immediately after the ACS event and the available data on plaque stabilization, and discuss treatment algorithms and clinical perspectives for the use of these agents in this clinical setting. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a highly prevalent condition associated with lipid accumulation in the intima layer of arterial blood vessels. The development of atherosclerotic plaques is associated with the incidence of major cardiovascular events, such as acute coronary syndrome or ischemic stroke. Due to the significant prevalence of atherosclerosis and its subclinical progression, it is associated with severe and potentially lethal complications. The pathogenesis of atherosclerosis is complex and not entirely known. The identification of novel non-invasive diagnostic markers and treatment methods that could suppress the progression of this condition is highly required. Non-coding RNA (ncRNA) involves several subclasses of RNA molecules. microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) differently regulate gene expression. Importantly, these molecules are frequently dysregulated under pathological conditions, which is associated with enhanced or suppressed expression of their target genes. In this review, we aim to discuss the involvement of ncRNA in crucial mechanisms implicated in the pathogenesis of atherosclerosis. We summarize current evidence on the potential use of these molecules as diagnostic and therapeutic targets. [ABSTRACT FROM AUTHOR]

The aim of this paper is to demonstrate the difference in usefulness of the coronary artery calcium score (CACS) and the full assessment of the severity of coronary artery disease in coronary computed tomography angiography (CCTA) studies. The difference between the population risk of coronary artery disease (CAD) assessed by the CACS and the severity of CAD was demonstrated in images from two CCTA studies. The first image is from a patient with a CACS of 0 and significant coronary artery stenosis. In the native phase of CCTA examination, no calcified changes were detected in the topography of the coronary arteries. In the middle section of the left descending artery (LAD), at the level of the second diagonal branch (Dg2), a large non-calcified atherosclerotic plaque was visible. Mid-LAD stenosis was estimated to be approximately 70%. The second image features a patient with a high CACS but no significant coronary artery stenosis. The calcium score of individual coronary arteries calculated using the Agatston method was as follows: left main (LM) 0, LAD 403, left circumflex (LCx) 207.7, right coronary artery (RCA) 12. CACS was 622.7, representing a significant population risk of significant CAD. In the proximal and middle sections of the LAD, numerous calcified and mixed atherosclerotic plaques with positive remodeling were visible, causing stenosis of 25–50%. Similarly, in the proximal and middle sections of the LCx, numerous calcified and mixed atherosclerotic plaques with positive remodeling were visualized, causing stenoses of 25–50%. Calcified atherosclerotic plaques were found in the RCA, causing stenosis <25%. The entire CCTA image met CAD-RADS 2 (coronary artery disease reporting and data system) criteria. In summary, CACS may be applicable in population-based studies to assess the risk of significant CAD. In the evaluation of individual patients, a comprehensive assessment of CAD severity based on the angiographic phase of the CCTA examination should be used. [ABSTRACT FROM AUTHOR]

Background: Diabetes contributes to a spectrum of complications encompassing microvascular and macrovascular disorders. This study aimed to explore the correlation between distal sensorimotor polyneuropathy (DSPN) severity and heightened carotid atherosclerosis among individuals with type 2 diabetes mellitus (T2DM). Method: Participants underwent comprehensive assessments including nerve conduction studies (NCS), Toronto Clinical Neuropathy Score (TCNS) evaluations, assessment of cardiometabolic risk factors, and carotid sonography studies covering dynamic and morphological parameters. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) in both the common carotid artery (CCA) and internal carotid artery (ICA), carotid intima-media thickness (IMT), and carotid plaque score (CPS) were also measured. Peripheral nerve function severity was assessed using composite amplitude scores (CAS) derived from NCS. Results: Individuals with DSPN exhibited lower EDV in the CCA and ICA (p < 0.0001 and p = 0.002), higher PI and RI in both CCA and ICA (all p < 0.0001), and higher CPS (p = 0.002). They also demonstrated a higher prevalence of retinopathy as an underlying condition, higher index HbA1c, and reduced estimated glomerular filtration rate (eGFR) (all p < 0.0001). Multiple linear regression analysis revealed significant associations where eGFR, ICA-PI, index HbA1c, waist circumference, and age were correlated with CAS. Meanwhile, diabetes duration, waist circumference, age, and index HbA1c showed significant associations with TCNS. Conclusions: Our study suggests that individuals with T2DM who exhibit more severe carotid atherosclerosis may not only be at increased risk of developing DSPN but also may experience greater severity of DSPN. PI in both the CCA and ICA, along with the CPS, serve as surrogate biomarkers for DSPN severity. [ABSTRACT FROM AUTHOR]

Background: The risk of cardiovascular disease (CVD) has traditionally been predicted via the assessment of carotid plaques. In the proposed study, AtheroEdge™ 3.0HDL (AtheroPoint™, Roseville, CA, USA) was designed to demonstrate how well the features obtained from carotid plaques determine the risk of CVD. We hypothesize that hybrid deep learning (HDL) will outperform unidirectional deep learning, bidirectional deep learning, and machine learning (ML) paradigms. Methodology: 500 people who had undergone targeted carotid B-mode ultrasonography and coronary angiography were included in the proposed study. ML feature selection was carried out using three different methods, namely principal component analysis (PCA) pooling, the chi-square test (CST), and the random forest regression (RFR) test. The unidirectional and bidirectional deep learning models were trained, and then six types of novel HDL-based models were designed for CVD risk stratification. The AtheroEdge™ 3.0HDL was scientifically validated using seen and unseen datasets while the reliability and statistical tests were conducted using CST along with p-value significance. The performance of AtheroEdge™ 3.0HDL was evaluated by measuring the p-value and area-under-the-curve for both seen and unseen data. Results: The HDL system showed an improvement of 30.20% (0.954 vs. 0.702) over the ML system using the seen datasets. The ML feature extraction analysis showed 70% of common features among all three methods. The generalization of AtheroEdge™ 3.0HDL showed less than 1% (p-value < 0.001) difference between seen and unseen data, complying with regulatory standards. Conclusions: The hypothesis for AtheroEdge™ 3.0HDL was scientifically validated, and the model was tested for reliability and stability and is further adaptable clinically. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory condition marked by endothelial dysfunction, lipid accumulation, inflammatory cell infiltration, and extracellular matrix (ECM) remodeling within arterial walls, leading to plaque formation and potential cardiovascular events. Key players in ECM remodeling and inflammation are matrix metalloproteinases (MMPs) and CD147/EMMPRIN, a cell surface glycoprotein expressed on endothelial cells, vascular smooth muscle cells (VSMCs), and immune cells, that regulates MMP activity. Hydrogen sulfide (H₂S), a gaseous signaling molecule, has emerged as a significant modulator of these processes including oxidative stress mitigation, inflammation reduction, and vascular remodeling. This systematic review investigates the mechanistic pathways through which H₂S influences MMPs and CD147/EMMPRIN and assesses its impact on atherosclerosis progression. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases, focusing on studies examining H₂S modulation of MMPs and CD147/EMMPRIN in atherosclerosis contexts. Findings indicate that H₂S modulates MMP expression and activity through transcriptional regulation and post-translational modifications, including S-sulfhydration. By mitigating oxidative stress, H₂S reduces MMP activation, contributing to plaque stability and vascular remodeling. H₂S also downregulates CD147/EMMPRIN expression via transcriptional pathways, diminishing inflammatory responses and vascular cellular proliferation within plaques. The dual regulatory role of H₂S in inhibiting MMP activity and downregulating CD147 suggests its potential as a therapeutic agent in stabilizing atherosclerotic plaques and mitigating inflammation. Further research is warranted to elucidate the precise molecular mechanisms and to explore H₂S-based therapies for clinical application in atherosclerosis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Acute ischemic stroke (AIS) is a leading cause of death and disability with poor long-term outcomes. Creating a predictive score for long-term mortality in AIS might be important for optimizing treatment strategies. The aim of this study is to develop and validate a predictive score for three-year mortality in patients with AIS using several demographic, clinical, laboratory and imaging parameters. Materials and Methods: This study included 244 AIS patients admitted to a tertiary center and followed up for three years. The patients' data included demographics, clinical features, laboratory tests (including resistin and leptin levels) and imaging parameters. The patients were randomly divided into a predictive group (n = 164) and a validation group (n = 80). Results: Advanced age, a high NIHSS score, low levels of hemoglobin, elevated resistin levels and the presence of carotid plaques were independently associated with three-year mortality. The predictive model incorporated these variables, and it was validated in a separate cohort. Leptin levels did not significantly predict mortality. Conclusions: This study developed and validated a promising predictive score for three-year mortality in patients with AIS. Advanced age, high NIHSS scores, low hemoglobin levels, elevated resistin levels and the presence of carotid plaques were the independent predictors of long-term mortality. [ABSTRACT FROM AUTHOR]

Stroke is the second leading cause of death and a major cause of disability around the world, and the development of atherosclerotic plaques in the carotid arteries is generally considered the leading cause of severe cerebrovascular events. In recent years, new reports have reinforced the role of an accurate histopathological analysis of carotid plaques to perform the stratification of affected patients and proceed to the correct prevention of complications. This work proposes applying an unsupervised learning approach to analyze complex whole-slide images (WSIs) of atherosclerotic carotid plaques to allow a simple and fast examination of their most relevant features. All the code developed for the present analysis is freely available. The proposed method offers qualitative and quantitative tools to assist pathologists in examining the complexity of whole-slide images of carotid atherosclerotic plaques more effectively. Nevertheless, future studies using supervised methods should provide evidence of the correspondence between the clusters estimated using the proposed textural-based approach and the regions manually annotated by expert pathologists. [ABSTRACT FROM AUTHOR]

Laminins are essential components of the basement membranes, expressed in a tissue- and cell-specific manner under physiological conditions. During inflammatory circumstances, such as atherosclerosis, alterations in laminin composition within vessels have been observed. Our study aimed to assess the influence of tumor necrosis factor-alpha (TNF), a proinflammatory cytokine abundantly found in atherosclerotic lesions, on endothelial laminin gene expression and the effects of laminin-332 (LN332) on endothelial cells' behavior. We also evaluated the expression of LN332-encoding genes in human carotid atherosclerotic plaques. Our findings demonstrate that TNF induces upregulation of LAMB3 and LAMC2, which, along with LAMA3, encode the LN332 isoform. Endothelial cells cultured on recombinant LN332 exhibit decreased claudin-5 expression and display a loosely connected phenotype, with an elevated expression of chemokines and leukocyte adhesion molecules, enhancing their attractiveness and adhesion to leukocytes in vitro. Furthermore, LAMB3 and LAMC2 are upregulated in human carotid plaques and show a positive correlation with TNF expression. In summary, TNF stimulates the expression of LN332-encoding genes in human endothelial cells and LN332 promotes an endothelial phenotype characterized by compromised junctional integrity and increased leukocyte interaction. These findings highlight the importance of basement membrane proteins for endothelial integrity and the potential role of LN332 in atherosclerosis. [ABSTRACT FROM AUTHOR]

Carotid stenosis is characterized by the progressive narrowing of the carotid arteries due to the formation of atherosclerotic plaque, which can lead to stroke and death as major complications. Numerous biomarkers allow for its study and characterization, particularly those related to "omics" sciences. Through the most common research databases, we report representative studies about carotid stenosis biomarkers based on genomics, transcriptomics, proteomics, and metabolomics in a narrative review. To establish a priority among studies based on their internal validity, we used a quality assessment tool, the Scale for the Assessment of Narrative Review Articles (SANRA). Genes, transcriptomes, proteins, and metabolites can diagnose the disease, define plaque connotations, predict consequences after revascularization interventions, and associate carotid stenosis with other patient comorbidities. It also emerged that many aspects determining the patient's psychological and social sphere are implicated in carotid disease. In conclusion, when taking the multidisciplinary approach that combines human sciences with biological sciences, it is possible to comprehensively define a patient's health and thus improve their clinical management through precision medicine. [ABSTRACT FROM AUTHOR]

Background: Depression is the most common mental illness worldwide and generates an enormous health and economic burden. Furthermore, it is known to be associated with an elevated risk of arteriosclerotic cardiovascular diseases (ASCVD), particularly stroke. However, it is not a factor reflected in many ASCVD risk models, including SCORE2. Thus, we analysed the relationship between depression, ASCVD and SCORE2 in our cohort. Methods: We analysed 9350 subjects from the Paracelsus 10,000 cohort, who underwent both a carotid artery ultrasound and completed a Beck Depression Inventory (BDI) screening. Patients were categorised binomially based on the BDI score. Atherosclerotic carotid plaque or absence was dichotomised for logistic regression modelling. Odds ratios and adjusted relative risks were calculated using Stata. Results: Subjects with an elevated BDI (≥14) had higher odds for carotid plaques compared to subjects with normal BDI, especially after adjusting for classical risk factors included in SCORE2 (1.21; 95%CI 1.03–1.43, p = 0.023). The adjusted relative risk for plaques was also increased (1.09; 95%CI 1.01–1.18, p = 0.021). Subgroup analysis showed an increased odds of plaques with increases in depressive symptoms, particularly in women and patients ≤55 yrs. Conclusions: In our cohort, the BDI score is associated with subclinical atherosclerosis beyond classical risk factors. Thus, depression might be an independent risk factor which may improve risk stratification if considered in ASCVD risk prediction models, such as SCORE2. Furthermore, reminding clinicians to take mental health into consideration to identify individuals at increased atherosclerosis risk may provide added opportunities to address measures which can reduce the risk of ASCVD. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a leading cause of cardiovascular disease, necessitates advanced and innovative modeling techniques to better understand and predict plaque dynamics. The present work presents two distinct hypothetical models inspired by different research fields: the logistic map from chaos theory and Markov models from stochastic processes. The logistic map effectively models the nonlinear progression and sudden changes in plaque stability, reflecting the chaotic nature of atherosclerotic events. In contrast, Markov models, including traditional Markov chains, spatial Markov models, and Markov random fields, provide a probabilistic framework to assess plaque stability and transitions. Spatial Markov models, visualized through heatmaps, highlight the spatial distribution of transition probabilities, emphasizing local interactions and dependencies. Markov random fields incorporate complex spatial interactions, inspired by advances in physics and computational biology, but present challenges in parameter estimation and computational complexity. While these hypothetical models offer promising insights, they require rigorous validation with real-world data to confirm their accuracy and applicability. This study underscores the importance of interdisciplinary approaches in developing theoretical models for atherosclerotic plaques. [ABSTRACT FROM AUTHOR]

CT angiography has become, in recent years, a main evaluating modality for patients with coronary artery disease (CAD). Recent advancements in the field have allowed us to identity not only the presence of obstructive disease but also the characteristics of identified lesions. High-risk coronary atherosclerotic plaques are identified in CT angiographies via a number of specific characteristics and may provide prognostic and therapeutic implications, aiming to prevent future ischemic events via optimizing medical treatment or providing coronary interventions. In light of new evidence evaluating the safety and efficacy of intervening in high-risk plaques, even in non-flow-limiting disease, we aim to provide a comprehensive review of the diagnostic algorithms and implications of plaque vulnerability in CT angiography, identify any differences with invasive imaging, analyze prognostic factors and potential future therapeutic options in such patients, as well as discuss new frontiers, including intervening in non-flow-limiting stenoses and the role of CT angiography in patient stratification. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a condition characterized by inflammation in the arteries, is the main cause of cardiovascular disease (CVD), including heart attacks and strokes. While current treatments focus on lowering cholesterol levels, new anti-inflammatory strategies are being explored as potential therapies for atherosclerosis. These strategies involve targeting the immune system's role in atherosclerosis and have shown promise in reducing CVD risk. However, challenges such as the risk of infections and individual variability in drug response need to be addressed. Advances in technologies like single-cell transcriptomics and PET imaging are aiding in the deeper understanding of the immune landscape of atherosclerosis and the identification of potential drug targets and biomarkers. These developments may lead to personalized therapies for atherosclerosis in the future. [Extracted from the article]

Background and Objectives: Atherosclerosis is one of the main reasons for cardiovascular disease development. This study aimed to analyze the association of mtDNA mutations and atherosclerotic plaques in carotid arteries of patients with atherosclerosis and conditionally healthy study participants from the Novosibirsk region. Methods: PCR fragments of DNA containing the regions of 10 investigated mtDNA mutations were pyrosequenced. The heteroplasmy levels of mtDNA mutations were analyzed using a quantitative method based on pyrosequencing technology developed by M. A. Sazonova and colleagues. Results: In the analysis of samples of patients with atherosclerotic plaques of the carotid arteries and conditionally healthy study participants from the Novosibirsk region, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected. A west–east gradient was found in the distribution of the mtDNA mutations m.5178C>A, m.3256C>T, m.652insG, and m.13513G>A. Conclusions: Therefore, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A, and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected in patients with atherosclerotic plaques in their carotid arteries from the Novosibirsk region. [ABSTRACT FROM AUTHOR]

Background and Objectives: Atherosclerotic disease is a major contributor to heart failure, stroke, and myocardial infarction, significantly lowering the quality of life and life expectancy and placing a significant burden on healthcare. Not all lesions deemed non-significant are benign, and conversely, not all significant lesions are causative of ischemia. Fractional flow reserve (FFR) provides a functional assessment of coronary lesions, while optical coherence tomography (OCT) offers detailed imaging of plaque morphology, aiding in therapeutic decision-making. The objective of this study was to evaluate the utility of OCT and FFR as adjunctive tools in the catheterization laboratory for guiding therapeutic decisions in patients with multivessel disease for non-culprit vessels. Specifically, we aimed to assess how OCT and FFR influence therapeutic decision-making in patients with multivessel coronary artery disease. Materials and Methods: A total of 36 patients with acute coronary syndrome (ACS) and multivessel disease were randomized 1:1 into two groups: one guided by FFR alone and the other by a combination of FFR and OCT. For the FFR group, revascularization decisions for non-culprit lesions were based solely on FFR measurements. If the FFR was >0.8, the procedure was concluded, and the patient received maximal medical treatment. If the FFR was ≤0.8, a stent was placed. For the FFR + OCT group, if the FFR was >0.8, the revascularization decision was based on OCT findings. If there were no vulnerable plaques (VP), the procedure was concluded, and the patient received maximal medical treatment. If OCT imaging indicated VP, then the patient underwent revascularization. If the FFR was ≤0.8, the patient underwent revascularization regardless of OCT findings. Results: OCT imaging altered the therapeutic decision in 11 cases where FFR measurements were above 0.8, but the lesions were characterized as VP. Analyzing the total change in the decision to stent, 4 cases in the FFR group and 15 cases in the FFR and OCT groups (4 based on FFR and 11 on OCT) revealed a statistically significant difference (p = 0.0006; Relative Risk = 0.2556; 95% CI: 0.1013 to 0.5603). When analyzing the change in the total decision both to stent and not to stent, we observed a statistically significant difference, with Group 1 having 7 cases and Group 2 having 15 cases (p = 0.0153; Relative Risk = 0.4050; 95% CI: 0.2004 to 0.7698. Conclusions: Based on the findings of this study, OCT significantly increases the percentage of stenting procedures by identifying vulnerable lesions. The use of intracoronary imaging facilitates the timely identification and treatment of these vulnerable lesions. This underscores the crucial role of OCT in enhancing the precision of coronary interventions by ensuring timely intervention for vulnerable lesions, thereby potentially improving patient outcomes. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is the leading cause of death globally and is a heart condition involving insufficient blood supply to the heart muscle due to atherosclerotic plaque formation. Atherosclerosis is a chronic disease in which plaques, made up of fat, cholesterol, calcium, and other substances, build up on the inner walls of arteries. Recently, there has been growing interest in finding reliable biomarkers to understand the pathogenesis and progression of atherosclerosis. Tissue Inhibitors of Metalloproteinases (TIMPs) have emerged as potential candidates for monitoring atherosclerotic development. TIMPs are a family of endogenous proteins that regulate matrix metalloproteinases (MMPs), enzymes involved in remodeling the extracellular matrix. A systematic search using Prisma guidelines was conducted and eleven studies were selected from four different databases: Web of Science (WOS), Scopus, Ovid, and PubMed. The Newcastle–Ottawa Scale (NOS) score was used to assess the risk of bias for each study. A meta-analysis was performed, and the hazard ratio (HR) and its 95% confidence interval (CI) were determined. Among the eleven studies, six reported a positive association between higher levels of TIMPs and an increased risk of atherosclerosis. Conversely, four studies support low TIMPs with high CAD risk and one study showed no significant association between TIMP-2 G-418C polymorphism and CAD. This divergence in findings underscores the complexity of the relationship between TIMPs, atherosclerosis, and CAD. In addition, a meta-analysis from two studies yielded a HR (95% CI) of 1.42 (1.16–1.74; p < 0.001; I2 = 0%) for TIMP-2 in predicting major adverse cardiovascular events (MACEs). In conclusion, the existing evidence supports the notion that TIMPs can serve as biomarkers for predicting the severity of atherosclerosis, myocardial damage, and future MACEs among CAD patients. However, further exploration is warranted through larger-scale human studies, coupled with in vitro and in vivo investigations. [ABSTRACT FROM AUTHOR]

Historically, cardiovascular prevention has been predominantly focused on stress-induced ischemia, but recent trials have challenged this paradigm, highlighting the emerging role of vulnerable, non-flow-limiting coronary plaques, leading to a shift towards integrating plaque morphology with functional data into risk prediction models. Coronary computed tomography angiography (CCTA) represents a high-resolution, low-risk, and largely available non-invasive modality for the precise delineation of plaque composition, morphology, and inflammatory activity, further enhancing our ability to stratify high-risk plaque and predict adverse cardiovascular outcomes. Coronary artery calcium (CAC) scoring, derived from CCTA, has emerged as a promising tool for predicting future cardiovascular events in asymptomatic individuals, demonstrating incremental prognostic value beyond traditional cardiovascular risk factors in terms of myocardial infarction, stroke, and all-cause mortality. Additionally, CCTA-derived information on adverse plaque characteristics, geometric characteristics, and hemodynamic forces provides valuable insights into plaque vulnerability and seems promising in guiding revascularization strategies. Additionally, non-invasive assessments of epicardial and pericoronary adipose tissue (PCAT) further refine risk stratification, adding prognostic significance to coronary artery disease (CAD), correlating with plaque development, vulnerability, and rupture. Moreover, CT imaging not only aids in risk stratification but is now emerging as a screening tool able to monitor CAD progression and treatment efficacy over time. Thus, the integration of CAC scoring and PCAT evaluation into risk stratification algorithms, as well as the identification of high-risk plaque morphology and adverse geometric and hemodynamic characteristics, holds promising results for guiding personalized preventive interventions, helping physicians in identifying high-risk individuals earlier, tailoring lifestyle and pharmacological interventions, and improving clinical outcomes in their patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic systemic inflammation is a risk factor that increases the development of atherosclerosis and predisposes to cardiovascular diseases (CVDs). The systemic inflammatory profile of alopecia areata (AA) regarding IFNγ and Th1 cytokine dysregulation has previously been described, suggesting an increased incidence of CVDs in this population. No previous studies investigated the possible relationship between atherosclerosis and AA by cardiovascular imaging techniques. To determine the prevalence, distribution and burden of subclinical atherosclerosis in AA. Methods: We conducted a case–control study in 62 participants, including 31 patients with severe AA (SALT > 75) and 31 healthy controls, matched for age, sex and body mass index (BMI). The participants underwent a detailed history assessment and were subjected to the measurement of weight, height, abdominal circumference and blood pressure. A fasting blood sample was also collected. Subclinical atherosclerosis was evaluated by ultrasonography of the bilateral femoral and carotid arteries. Results: The AA patients had an increased prevalence of subclinical atherosclerosis (54.7%) compared to the healthy controls (22.6%, p = 0.010). The prevalence of atheroma plaques was significantly higher in the carotid arteries (41.90% vs. 12.9%, p = 0.009), while no significant differences were found in femoral plaque prevalence. The AA patients with atherosclerotic plaques were older (p < 0.001) and had a longer time since AA diagnosis (p = 0.11) and increased serum levels of glycated hemoglobin (p = 0.029) and triglycerides (p = 0.009). In a regression analysis, duration of disease and neutrophil/lymphocyte ratio were the main predictors of atherosclerosis. Conclusions: AA patients have an increased prevalence of carotid subclinical atherosclerosis. The duration of AA, systemic inflammation and insulin resistance appear to play a role in the development of subclinical atherosclerosis in this population. [ABSTRACT FROM AUTHOR]

Acute limb ischemia (ALI) is defined as a sudden reduction in blood flow to a limb, resulting in cessation of blood flow and, therefore, cessation of the delivery of nutrients and oxygen to the tissues of the lower limb. Despite optimal treatment to restore blood flow to ischemic tissues, some patients may suffer from ischemia/reperfusion (I/R) syndrome, the most severe complication after a revascularization procedure used to restore blood flow. There are multiple molecular and cellular factors that are involved in each phase of ALI. This review focuses firstly on molecular and cellular factors of arterial thrombosis, highlighting the role of atherosclerotic plaques, smooth muscle cells (SMCs), and cytokine which may alter key components of the extracellular matrix (ECM). Then, molecular and cellular factors of arterial embolism will be discussed, highlighting the importance of thrombi composition. Molecular and cellular factors of ischemia/reperfusion syndrome are analyzed in depth, highlighting several important mechanisms related to tissue damage, such as inflammation, apoptosis, autophagy, necrosis, and necroptosis. Furthermore, local and general complications of ALI are discussed in the context of molecular alterations. Ultimately, the role of novel biomarkers and targeted therapies is discussed. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is the formation of atherosclerotic plaques on the walls of the arteries, causing them to narrow. If this occurs in the coronary arteries, the blood vessels may be completely blocked, resulting in myocardial infarction; if it occurs in the blood vessels of the brain, the blood vessels may be blocked, resulting in cerebral infarction, i.e., stroke. Studies have shown that the pathogenesis of atherosclerosis involves the processes of inflammation, lipid infiltration, oxidative stress, and endothelial damage, etc. SIRT, as a key factor regulating the molecular mechanisms of oxidative stress, inflammation, and aging, has an important impact on the pathogenesis of plaque formation, progression, and vulnerability. Statistics show that AS accounts for about 50 per cent of deaths in Western countries. Currently, oral medication is the mainstay of AS treatment, but its development is limited by side effects, low bioavailability and other unfavourable factors. In recent years, with the rapid development of nano-preparations, researchers have combined statins and natural product drugs within nanopreparations to improve their bioavailability. Based on this, this paper summarises the main pathogenesis of AS and also proposes new oral nanoformulations such as liposomes, nanoparticles, nanoemulsions, and nanocapsules to improve their application in the treatment of AS. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) constitutes the most common cause of death worldwide. In Europe alone, approximately 4 million people die annually due to CVD. The leading component of CVD leading to mortality is myocardial infarction (MI). MI is classified into several types. Type 1 is associated with atherosclerosis, type 2 results from inadequate oxygen supply to cardiomyocytes, type 3 is defined as sudden cardiac death, while types 4 and 5 are associated with procedures such as percutaneous coronary intervention and coronary artery bypass grafting, respectively. Of particular note is type 1, which is also the most frequently occurring form of MI. Factors predisposing to its occurrence include, among others, high levels of low-density lipoprotein cholesterol (LDL-C) in the blood, cigarette smoking, chronic kidney disease (CKD), diabetes mellitus (DM), hypertension, and familial hypercholesterolaemia (FH). The primary objective of this review is to elucidate the issues with regard to type 1 MI. Our paper delves into, amidst other aspects, its pathogenesis, risk assessment, diagnosis, pharmacotherapy, and interventional treatment options in both acute and long-term conditions. [ABSTRACT FROM AUTHOR]

High-density lipoprotein (HDL) is a group of small, dense, and protein-rich lipoproteins that play a role in cholesterol metabolism and various cellular processes. Decreased levels of HDL and HDL dysfunction are commonly observed in individuals with type 2 diabetes mellitus (T2DM), which is also associated with an increased risk for cardiovascular disease (CVD). Due to hyperglycemia, oxidative stress, and inflammation that develop in T2DM, HDL undergoes several post-translational modifications such as glycation, oxidation, and carbamylation, as well as other alterations in its lipid and protein composition. It is increasingly recognized that the generation of HDL modifications in T2DM seems to be the main cause of HDL dysfunction and may in turn influence the development and progression of T2DM and its related cardiovascular complications. This review provides a general introduction to HDL structure and function and summarizes the main modifications of HDL that occur in T2DM. Furthermore, the potential impact of HDL modifications on the pathogenesis of T2DM and CVD, based on the altered interactions between modified HDL and various cell types that are involved in glucose homeostasis and atherosclerotic plaque generation, will be discussed. In addition, some perspectives for future research regarding the T2DM-related HDL modifications are addressed. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a common form of cardiovascular disease, which is one of the most prevalent causes of death worldwide, particularly among older individuals. Surgery is the mainstay of treatment for severe stenotic lesions, though the rate of restenosis remains relatively high. Current medication therapy for atherosclerosis has limited efficacy in reversing the formation of atherosclerotic plaques. The search for new drug treatment options is imminent. Some potent medications have shown surprising therapeutic benefits in inhibiting inflammation and endothelial proliferation in plaques. Unfortunately, their use is restricted due to notable dose-dependent systemic side effects or degradation. Nevertheless, with advances in nanotechnology, an increasing number of nano-related medical applications are emerging, such as nano-drug delivery, nano-imaging, nanorobots, and so forth, which allow for restrictions on the use of novel atherosclerotic drugs to be lifted. This paper reviews new perspectives on the targeted delivery of nanoparticles to blood vessels for the treatment of atherosclerosis in both systemic and local drug delivery. In systemic drug delivery, nanoparticles inhibit drug degradation and reduce systemic toxicity through passive and active pathways. To further enhance the precise release of drugs, the localized delivery of nanoparticles can also be accomplished through blood vessel wall injection or using endovascular interventional devices coated with nanoparticles. Overall, nanotechnology holds boundless potential for the diagnosis and treatment of atherosclerotic diseases in the future. [ABSTRACT FROM AUTHOR]

The thymus represents a primary organ of the immune system, harboring the generation and maturation of T lymphocytes. Starting from childhood, the thymus undergoes involution, being replaced with adipose tissue, and by an advanced age nearly all the thymus parenchyma is represented by adipocytes. This decline of thymic function is associated with compromised maturation and selection of T lymphocytes, which may directly impact the development of inflammation and induce various autoinflammatory disorders, including atherosclerosis. For a long time, thymus health in adults has been ignored. The process of adipogenesis in thymus and impact of thymic fat on cardiometabolism remains a mysterious process, with many issues being still unresolved. Meanwhile, thymus functional activity has a potential to be regulated, since islets of thymopoeisis remain in adults even at an advanced age. The present review describes the intricate process of thymic adipose involution, focusing on the issues of the thymus' role in the development of atherosclerosis and metabolic health, tightly interconnected with the state of vessels. We also review the recent information on the key molecular pathways and biologically active substances that may be targeted to manipulate both thymic function and atherosclerosis. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) and myocardial infarction (MI) remain leading causes of death and disability worldwide. CAD begins with the formation of atherosclerotic plaques within the intimal layer of the coronary arteries, a process driven by persistent arterial inflammation and oxidation. Myeloperoxidase (MPO), a mammalian haem peroxidase enzyme primarily expressed within neutrophils and monocytes, has been increasingly recognised as a key pro-inflammatory and oxidative enzyme promoting the development of vulnerable coronary atherosclerotic plaques that are prone to rupture, and can precipitate a MI. Mounting evidence also implicates a pathogenic role for MPO in the inflammatory process that follows a MI, which is characterised by the rapid infiltration of activated neutrophils into the damaged myocardium and the release of MPO. Excessive and persistent cardiac inflammation impairs normal cardiac healing post-MI, resulting in adverse cardiac outcomes and poorer long-term cardiac function, and eventually heart failure. This review summarises the evidence for MPO as a significant oxidative enzyme contributing to the inappropriate inflammatory responses driving the progression of CAD and poor cardiac healing after a MI. It also details the proposed mechanisms underlying MPO's pathogenic actions and explores MPO as a novel therapeutic target for the treatment of unstable CAD and cardiac damage post-MI. [ABSTRACT FROM AUTHOR]

Background: Carotid stenosis (CS) is an atherosclerotic disease of the carotid artery that can lead to devastating cardiovascular outcomes such as stroke, disability, and death. The currently available treatment for CS is medical management through risk reduction, including control of hypertension, diabetes, and/or hypercholesterolemia. Surgical interventions are currently suggested for patients with symptomatic disease with stenosis >50%, where patients have suffered from a carotid-related event such as a cerebrovascular accident, or asymptomatic disease with stenosis >60% if the long-term risk of death is <3%. There is a lack of current plasma protein biomarkers available to predict patients at risk of such adverse events. Methods: In this study, we investigated several growth factors and biomarkers of inflammation as potential biomarkers for adverse CS events such as stroke, need for surgical intervention, myocardial infarction, and cardiovascular-related death. In this pilot study, we use a support vector machine (SVM), random forest models, and the following four significantly elevated biomarkers: C-X-C Motif Chemokine Ligand 6 (CXCL6); Interleukin-2 (IL-2); Galectin-9; and angiopoietin-like protein (ANGPTL4). Results: Our SVM model best predicted carotid cerebrovascular events with an area under the curve (AUC) of >0.8 and an accuracy of 0.88, demonstrating strong prognostic capability. Conclusions: Our SVM model may be used for risk stratification of patients with CS to determine those who may benefit from surgical intervention. [ABSTRACT FROM AUTHOR]

Atherosclerosis continues to be a leading cause of morbidity and mortality globally. The precise evaluation of the extent of an atherosclerotic plaque is essential for forecasting its likelihood of causing health concerns and tracking treatment outcomes. When compared to conventional methods used, nanoparticles offer clear benefits and excellent development opportunities for the detection and characterisation of susceptible atherosclerotic plaques. In this review, we analyse the recent advancements of nanoparticles as theranostics in the management of atherosclerosis, with an emphasis on applications in drug delivery. Furthermore, the main issues that must be resolved in order to advance clinical utility and future developments of NP research are discussed. It is anticipated that medical NPs will develop into complex and advanced next-generation nanobotics that can carry out a variety of functions in the bloodstream. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory condition affecting 2% of the Western population. It includes diverse manifestations influenced by genetic predisposition, environmental factors, and immune status. The sustained activation of mTOR is a key element in psoriasis pathogenesis, leading to an uncontrolled proliferation of cytokines. Furthermore, mTOR activation has been linked with the transition from psoriasis to non-skin manifestations such as psoriatic arthritis and cardiovascular events. While therapies targeting pro-inflammatory cytokines have shown efficacy, additional pathways may offer therapeutic potential. The PI3K/Akt/mTOR pathway, known for its role in cell growth, proliferation, and metabolism, has emerged as a potential therapeutic target in psoriasis. This review explores the relevance of mTOR in psoriasis pathophysiology, focusing on its involvement in cutaneous and atheromatous plaque proliferation, psoriatic arthritis, and cardiovascular disease. The activation of mTOR promotes keratinocyte and synovial cell proliferation, contributing to plaque formation and joint inflammation. Moreover, mTOR activation may exacerbate the cardiovascular risk by promoting pro-inflammatory cytokine production and dysregulation lipid and glucose metabolism. The inhibition of mTOR has shown promise in preclinical studies, reducing skin inflammation and plaque proliferation. Furthermore, mTOR inhibition may mitigate cardiovascular risk by modulating cholesterol metabolism and attenuating atherosclerosis progression. Understanding the role of mTOR in psoriasis, psoriatic arthritis, and cardiovascular disease provides insight into the potential treatment avenues and sheds light on the complex interplay of the immune and metabolic pathways in these conditions. [ABSTRACT FROM AUTHOR]

In the study of coronary artery disease (CAD), the mechanism of plaque formation and development is still an important subject for investigation. A limitation of current coronary angiography (CAG) is that it can only show static images of the narrowing of arterial channels without identifying the mechanism of the disease or predicting its progression or regression. To address this limitation, the CAG technique has been modified. The new approach emphasizes identifying and analyzing blood flow patterns, employing methodologies akin to those used by hydraulic engineers for fluid or gas movement through domestic or industrial pipes and pumps. With the new technique, various flow patterns and arterial phenomena—such as laminar, turbulent, antegrade, retrograde, and recirculating flow and potentially water hammer shock and vortex formation—are identified, recorded, and classified. These phenomena are then correlated with the presence of lesions at different locations within the coronary vasculature. The formation and growth of these lesions are explained from the perspective of fluid mechanics. As the pathophysiology of CAD and other cardiovascular conditions becomes clearer, new medical, surgical, and interventional treatments could be developed to reverse abnormal coronary flow dynamics and restore laminar flow, leading to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

The rupture of unstable plaques is a major cause of acute cardiovascular events. The early assessment of carotid plaques can significantly reduce the cardiovascular risks, so developing evaluation models suitable for data from different centers is of great clinical importance. This study leverages plaque datasets from multiple centers to develop a Weighted multi-source carotid artery plaque Unsupervised Classification Framework (WUCF). The multi-source domain adaptation module of the WUCF focuses on maintaining feature consistency between each independent source and target center, while also integrating a specialized domain discriminator expert. This ensures that the knowledge from each source center is effectively learned and combined for accurate predictions in the target domain. The experimental evaluation of WUCF, using datasets from three centers, has demonstrated the method's superiority and robustness. [ABSTRACT FROM AUTHOR]

Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel of the neointimal layer of the atherosclerotic plaque that can support thrombogenesis upon exposure to human blood. A biomimetic hydrogel of the neointima was produced by culturing THP-1-derived foam cells within 3D collagen hydrogels in the presence or absence of atorvastatin. Prothrombin time and platelet aggregation onset were measured after exposure of the neointimal models to platelet-poor plasma and washed platelet suspensions prepared from blood of healthy, medication-free volunteers. Activity of the extrinsic coagulation pathway was measured using the fluorogenic substrate SN-17. Foam cell formation was observed following preincubation of the neointimal biomimetic hydrogels with oxidized LDL, and this was inhibited by pretreatment with atorvastatin. The neointimal biomimetic hydrogel was able to trigger platelet aggregation and blood coagulation upon exposure to human blood products. Atorvastatin pretreatment of the neointimal biomimetic layer significantly reduced its pro-aggregatory and pro-coagulant properties. In the future, this 3D neointimal biomimetic hydrogel can be incorporated as an additional layer within our current thrombus-on-a-chip model to permit the study of atherosclerosis development and the screening of anti-thrombotic drugs as an alternative to current animal models. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains a prominent cause of global mortality, primarily driven by atherosclerosis. Diabetes mellitus, as a modifiable risk factor, significantly contributes to atherogenesis. Monocyte recruitment to the intima is a critical step in atherosclerotic plaque formation, involving chemokines and adhesion molecules such as selectins, ICAM-1, and MCP-1. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a promising group of drugs for reducing cardiovascular risk in diabetic patients, prompting investigation into their mechanisms of action. This interventional study enrolled 50 diabetes patients with atherosclerotic plaque, administering GLP-1RA for 180 days. Serum concentrations of MCP-1, ICAM-1, and L-selectin were measured before and after treatment. Anthropometric and biochemical parameters were also assessed. GLP-1RA treatment resulted in significant improvements in anthropometric parameters, glycemic control, blood pressure, and biochemical markers of liver steatosis. Biomarker laboratory analysis revealed higher baseline levels of MCP-1, ICAM-1, and L-selectin in diabetic patients with atherosclerotic plaque compared to healthy controls. Following treatment, MCP-1 and L-selectin levels decreased significantly (p < 0.001), while ICAM-1 levels increased (p < 0.001). GLP-1RA treatment in diabetic patients with atherosclerotic plaque leads to favorable changes in serum molecule levels associated with monocyte recruitment to the endothelium. The observed reduction in MCP-1 and L-selectin suggests a potential mechanism underlying GLP-1RA-mediated cardiovascular risk reduction. Further research is warranted to elucidate the precise mechanisms and clinical implications of these findings in diabetic patients with atherosclerosis. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the relationship between the presence of atherosclerotic lesions in the carotid arteries detected by ultrasound and the occurrence of atherosclerosis in the coronary arteries determined by computed tomography (CT) in patients with arterial hypertension (HTA). A total of 83 patients with HTA were qualified for the study (age: 71.3 ± 8.5 years). All subjects underwent carotid arteries ultrasound and coronary arteries CT. The carotid plaque score was assessed using ultrasound. The studied group was divided into two subgroups: a subgroup with the carotid plaque score ≤ 1 (A) and a subgroup with carotid plaque score ≥2 (B). Coronary arteries CT assessed coronary artery calcium score (CACS) and degree of coronary stenosis based on CAD-RADS. In subgroup B, a significantly higher CACS (411.3 ± 70.1 vs. 93.5 ± 31.8) and significantly higher grade in the CAD-RADS classification were demonstrated than in subgroup A (CAD-RADS ≥ 3: 21.8 vs. 6.0%). The regression analysis showed that carotid plaque score and age are independent risk factors for the severity of atherosclerotic lesions in the coronary arteries. In summary, ultrasound assessment of the carotid plaque score in patients with HTA could be considered as surrogate indicator of the risk and severity of atherosclerotic changes in the coronary arteries, but further studies are necessary to corroborate these results. [ABSTRACT FROM AUTHOR]

Atherosclerotic plaque buildup in the coronary and carotid arteries is pivotal in the onset of acute myocardial infarctions or cerebrovascular events, leading to heightened levels of illness and death. Atherosclerosis is a complex and multistep disease, beginning with the deposition of low-density lipoproteins in the arterial intima and culminating in plaque rupture. Modern technology favors non-invasive imaging techniques to assess atherosclerotic plaque and offer insights beyond mere artery stenosis. Among these, computed tomography stands out for its widespread clinical adoption and is prized for its speed and accessibility. Nonetheless, some limitations persist. The introduction of photon-counting computed tomography (PCCT), with its multi-energy capabilities, enhanced spatial resolution, and superior soft tissue contrast with minimal electronic noise, brings significant advantages to carotid and coronary artery imaging, enabling a more comprehensive examination of atherosclerotic plaque composition. This narrative review aims to provide a comprehensive overview of the main concepts related to PCCT. Additionally, we aim to explore the existing literature on the clinical application of PCCT in assessing atherosclerotic plaque. Finally, we will examine the advantages and limitations of this recently introduced technology. [ABSTRACT FROM AUTHOR]

Background: In atherothrombotic acute ischemic stroke (AIS), when the atheroma breaks down, the clot can incorporate foam cells (FCs). The identification of the correct etiology is paramount for secondary stroke prevention. This study aims to evaluate the presence of the FC in the arterial clot, and to determine whether patients with FCs and patients without FCs (NFCs) had different cerebrovascular risk factors, haemato-chemical parameters, and atherosclerotic disease incidence, in order to predict the etiological diagnosis. Methods: We collected 100 clots retrieved by mechanical thrombectomy from 495 consecutive AIS patients with large vessel occlusion. An expert pathologist evaluated the FC presence by histological examination stained with hematoxylin and eosin. Results: We observed FCs in 29/100 (29%) of retrieved clots and divided the patients into two groups, with/without FCs. The two groups had similar clinical and laboratory features, with a discrepancy between the FC presence in the clot and the clinical etiological diagnosis, even if not statistically significant. Conclusions: Our study showed the presence of FCs in approximately one-third of the retrieved clots, but the identification of the clot that presumably comes from the atheromatous plaque rupture tended to disagree with the clinical diagnosis. Future studies may reveal their potential to disclose clot origin or specific patient characteristics, guiding treatment options. [ABSTRACT FROM AUTHOR]

According to the World Health Organization, ischemic stroke is the second leading cause of death in the world. Frequently, it is caused by brachiocephalic artery (BCA) atherosclerosis. Timely detection of atherosclerosis and its unstable course can allow for a timely response to potentially dangerous changes and reduce the risk of vascular complications. Omics technologies allow us to identify new biomarkers that we can use in diagnosing diseases. This research included 90 blood plasma samples. The study group comprised 52 patients with severe atherosclerotic lesions BCA, and the control group comprised 38 patients with no BCA atherosclerosis. Targeted and panoramic lipidomic profiling of their blood plasma was carried out. There was a statistically significant difference (p < 0.05) in the values of the indices saturated fatty acids (FAs), unsaturated FAs, monounsaturated FAs, omega-3, and omega-6. Based on the results on the blood plasma lipidome, we formed models that have a fairly good ability to determine atherosclerotic lesions of the brachiocephalic arteries, as well as a model for identifying unstable atherosclerotic plaques. According only to the panoramic lipidome data, divided into groups according to stable and unstable atherosclerotic plaques, a significant difference was taken into account: p value < 0.05 and abs (fold change) > 2. Unfortunately, we did not observe significant differences according to the established plasma panoramic lipidome criteria between patients with stable and unstable plaques. Omics technologies allow us to obtain data about any changes in the body. According to our data, statistically significant differences in lipidomic profiling were obtained when comparing groups with or without BCA atherosclerosis. [ABSTRACT FROM AUTHOR]