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This study investigated the effects of ibandronate (IBN) on cardiomyopathy remodeling in diabetic rats. A rat model of diabetic cardiomyopathy (DCM) was established by supplementing them with a high-calorie diet combined with a low dose of streptozotocin (STZ). The diabetic rats received IBN (5 µg/kg per day) or normal saline subcutaneously for 16 weeks. The hematoxylin and eosin (HE) and Masson's trichrome staining were performed for evaluating the myocardial morphologies of the rats. Echocardiography and cardiac catheter were performed to assess their cardiac functional parameters. The protein levels of connective tissue growth factor (CTGF), farnesyl pyrophosphate synthase (FPPS), and mitogen-activated protein kinase (MAPK) were determined using Western blot analysis. RhoA activation was detected using a small GTP protease-linked immunosorbent assay (GLISA). The diabetic rats showed the development of moderate hyperglycemia, insulin resistance, hyperlipidemia, myocardial fibrosis, FPPS overexpression, cardiac systolic, and diastolic dysfunction. Inhibiting the FPPS could ameliorate myocardial hypertrophy and fibrosis. These anatomical findings were accompanied by a significant improvement in heart function. Furthermore, the inhibition of FPPS, the increased activation of RhoA, and phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 in DCM decreased significantly with the treatment of IBN. This study for the first time demonstrated that the upregulation of FPPS expression might be involved in diabetic myocardial remodeling in diabetes mellitus (DM). In addition, IBN might exert its inhibitory effects on myocardial tissue remodeling by suppressing the RhoA/ERK1/2 and RhoA/p38 MAPK pathways in DCM.

Bisphenol A (BPA) exposure may be positively associated with cardiovascular disease (CVD). For more than a past decade, exposure to bisphenol F (BPF) and bisphenol S (BPS), as substitutes for BPA, has gradually increased in the population. Whether BPF and BPS exposure are associated with CVD remains unclear. We used data from the United States National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016. A total of 3,502 participants, including 368 with CVD, were enrolled in the final analysis. Associations of BPA, BPF and BPS with CVD were determined using multivariate logistic regression analysis. The highest level of urinary BPA (≥2.5 ng/ml) was significantly associated with a higher CVD prevalence (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.08-2.3) among all participants in the quartile analysis. In stratified analyses, the highest level of urinary BPA was positively associated with CVD prevalence in males (1.86, 1.1-3.13) and the elderly population (≥60 years old) (1.89, 1.2-2.97). Higher levels of urinary BPF were positively associated with CVD prevalence in females (Q2: 1.81, 1.03-3.18; Q4: 1.73, 1.07-2.79) and in the elderly population (Q3: 1.7, 1.16-2.48). No associations were found between urinary BPS levels and CVD, regardless of whether the participants were stratified by age or sex. In conclusion, exposure to BPA or BPF was positively correlated with CVD prevalence, but an association was not found for exposure to BPS. BPF may not be as safe as assumed for human health.

To investigate the impact of visceral adipose tissue (VAT) on atherosclerosis in type 2 diabetes patients with normal bodyweight (OB[-]) in the Chinese population, and to further assess the sex-age differences between them.A total of 8,839 type 2 diabetes patients from two of the National Metabolic Management Centers in China were included in this study. Participants were classified into four groups by visceral fat area (VFA; cmThe VA(+)OB(-) prevalence was 3.7% among these participants. Patients with VA(+)OB(-) had the highest baPWV value (P 0.001) and the highest proportion of the tertile 3 of baPWV (P 0.001) among four groups, and were significantly associated with baPWV (standardized β = 0.026, P = 0.008). VFA was significantly related to tertile 2 to tertile 3 of baPWV in (OB[-]) type 2 diabetes patients, when compared with tertile 1 of baPWV, respectively. In sex-age stratified analysis, the association of VFA and the tertiles of baPWV showed sex differences. For the 55 years age stratification analysis, there was no age difference in the relationship between VFA and baPWV in (OB[-]) patients.Increased VAT was an independent risk factor for atherosclerosis in female type 2 diabetes patients with normal weight.

In patients with coronary artery disease who are being evaluated for percutaneous coronary intervention (PCI), procedures can be guided by fractional flow reserve (FFR) or intravascular ultrasonography (IVUS) for decision making regarding revascularization and stent implantation. However, the differences in clinical outcomes when only one method is used for both purposes are unclear.We randomly assigned 1682 patients who were being evaluated for PCI for the treatment of intermediate stenosis (40 to 70% occlusion by visual estimation on coronary angiography) in a 1:1 ratio to undergo either an FFR-guided or IVUS-guided procedure. FFR or IVUS was to be used to determine whether to perform PCI and to assess PCI success. In the FFR group, PCI was to be performed if the FFR was 0.80 or less. In the IVUS group, the criteria for PCI were a minimal lumen area measuring either 3 mmThe frequency of PCI was 44.4% among patients in the FFR group and 65.3% among those in the IVUS group. At 24 months, a primary-outcome event had occurred in 8.1% of the patients in the FFR group and in 8.5% of those in the IVUS group (absolute difference, -0.4 percentage points; upper boundary of the one-sided 97.5% confidence interval, 2.2 percentage points; P = 0.01 for noninferiority). Patient-reported outcomes as reported on the Seattle Angina Questionnaire were similar in the two groups.In patients with intermediate stenosis who were being evaluated for PCI, FFR guidance was noninferior to IVUS guidance with respect to the composite primary outcome of death, myocardial infarction, or revascularization at 24 months. (Funded by Boston Scientific; FLAVOUR ClinicalTrials.gov number, NCT02673424.).

Background: Coronary computed tomography-derived fractional reserve fraction (CT-FFR) and intravascular ultrasound-derived fractional reserve fraction (IVUS-FFR) are methods of functional assessment based on coronary imaging; however, the calculation algorithms are substantially different between them. The aim of this study was to compare diagnostic performance between CT-FFR and IVUS-FFR using invasive fractional flow reserve (FFR) as the reference standard. Method: Our retrospective study enrolled 40 patients (41 lesions) with known or suspected coronary artery disease (CAD) between January 2020 and July 2021. Patients who completed coronary CT angiography (CCTA) within six months underwent intravascular ultrasound (IVUS) and fractional flow reserve (FFR) evaluation. We used a novel CFD-based model (AccuFFRct, ArteryFlow Technology Co., Ltd., Hangzhou, China) to compute the CT-FFR values, and a novel software (AccuFFRivus, ArteryFlow Technology Co., Ltd., Hangzhou, China) to calculate the IVUS-FFR values coupled with angiography. The diagnostic performance of CT-FFR and IVUS-FFR was evaluated using invasive FFR≤0.8 as the reference standard. Result: AccuFFRivus demonstrated a strong correlation with invasive FFR (R=0.7913, PConclusions: IVUS-FFR may also become a new clinically meaningful functional evaluation method for diagnosing myocardial ischemia and may be as important as CT-FFR, Angio-FFR, OCT-FFR, and invasive FFR in the future as a method for evaluating coronary artery disease.

Background Abdominal aortic aneurysm (AAA) is a deadly disease in the elderly population. Currently, the association between single nucleotide polymorphisms (SNPs) and the presence of AAAs has become a hot topic and is a concern for many researchers. Method We performed a document retrieval in PubMed, EMBASE, and the Cochrane Library (to January 2020). A total of 17 case-control reports on SNPs of AAAs and eight SNPs of correlation factors were selected. All essential data, including race, age, country, criteria of AAA diagnosis, method of AAA measurement, method of genotype detection, name of SNPs, minor allele frequency (MAF), Hardy Weinberg equilibrium (HWE) of the control group, and number of cases and control groups were extracted by two reviewers independently. The fixed-effect model and random-effect model were used to calculate the overall odds ratios (ORs) and 95% confidence intervals (CIs). The association between selected SNPs and the presence of AAAs was evaluated under different genetic models (dominant, codominant, recessive, overdominant, and allele models). Results A total of 17 articles (sample size ranging from to 42–665 AAA cases and 49–2,297 controls) and 23 SNPs of related factors were identified. Eight SNPs were assessed in at least two studies and were selected for further meta-analysis. We found that the A allele of interleukin (IL)-10 (−1082 G/A) (OR: 1.35, 95% CI: 1.18–1.54, p < 0.0001) was a risk factor for AAAs under random and fixed-effect models. In addition, partial genetic models of these SNPs were confirmed to be related to the presence of AAA. Subgroup analysis revealed that haptoglobin (HP)-1 was a risk factor for AAAs (OR: 1.30, 95% CI: 1.04–1.63, p = 0.02) in the European population. No association was found between the occurrence of AAA and the other SNPs. Conclusion In our current meta-analysis, we speculated that the genotype distribution of IL-10 (−1082 G/A) may be associated with the emergence of AAA.

BACKGROUND: Non-invasive fractional flow reserve (FFR) has been increasingly used in the clinical workflow to assist clinical decision-making for percutaneous coronary intervention (PCI). This clinical study evaluates the diagnostic accuracy of coronary stenosis assessed by a non-invasive FFR analysis method (termed AccuFFRangio) based on invasive coronary angiography (ICA). It is a blinded, self-controlled, retrospective, and dual-center clinical investigation study. METHODS: Coronary angiography data and the related information of 320 patients with 320 vessels were collected, and AccuFFRangio was used to assess the FFR for these patients. Compared with the wire-measured FFR values, we evaluated AccuFFRangio performance by its accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The diagnostic accuracy, sensitivity, specificity, PPV, and NPV for AccuFFRangio in identifying hemodynamically significant coronary stenosis were 93.3%, 92.6%, 93.5%, 84.3%, and 97.1%, respectively. The direct correlation between computed AccuFFRangio and measured FFR was 0.812 (P

Platelets can protect from lipopolysaccharide-induced septic shock by inhibiting inflammation, but it is unknown whether platelets have an anti-atherosclerotic effect. The aim of this study was to investigate the effect of platelet transfusion on atherosclerosis (AS) in a mouse model of AS. Apolipoprotein E deficiency (ApoE(−/−)) mice were fed with a high-fat diet (HFD) for 8 weeks to establish a mouse model of AS. Mice weekly underwent bi-weekly injection with or without platelets during AS induction (HFD+platelet). Hematoxylin–eosin (H&E), Oil Red O, and Sudan IV stainings were used to assess pathological and morphological changes in the aortic tissue. Lipid levels, and liver and kidney function were examined using an automatic biochemical analyzer. Immune histochemical assays were used to detect the infiltration and distribution of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, and monocyte chemotactic protein-1 (MCP-1) in the aortic arch. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to examine the expression levels of TNF-α, IL-1β, IL-6, and MCP-1 in the aorta or the peripheral blood, respectively. Compared with the HFD group, AS pathological lesions from the aortic arch in the HFD+platelet group were significantly smaller and alterations in the lipid metabolism were also less pronounced. Furthermore, TNF-α, IL-1β, IL-6, and MCP-1 levels were all significantly reduced in mice that received platelet injection. Platelets transfusion can effectively ameliorate lipid metabolism, suppress the inflammatory response in the vascular wall, and inhibit the development of AS in mice.

Sulfated galactofucan (SWZ-4), which was extracted from Sargassum thunbergii, has recently been reported to show anti-inflammatory and anticancer properties. The present study aimed to evaluate whether SWZ-4 attenuates atherosclerosis in apolipoprotein E-knockout (ApoE-KO) mice by suppressing the inflammatory response through the TLR4/MyD88/NF-κB signaling pathway.Male ApoE-KO mice were fed with a high-fat diet for 16 weeks and intraperitoneally injected with SWZ-4. RAW246.7 cells were treated with lipopolysaccharide (LPS) and SWZ-4. Atherosclerotic lesions were measured by Sudan IV and oil red O staining. Serum lipid profiles, inflammatory cytokines, and mRNA and protein expression levels were evaluated.SWZ-4 decreased serum TNF-α, IL-6 and IL-1 levels, but did not reduce blood lipid profiles. SWZ-4 downregulated the mRNA and protein expression of TLR4 and MyD88, reduced the phosphorylation of p65, and attenuated atherosclerosis in the ApoE-KO mice (p0.01). In LPS-stimulated RAW 264.7 cells, SWZ-4 inhibited proinflammatory cytokine production and the mRNA expression of TLR4, MyD88, and p65 and reduced the protein expression of TLR4 and MyD88 and the phosphorylation of p65 (p0.01).These results suggest that SWZ-4 may exert an anti-inflammatory effect on ApoE-KO atherosclerotic mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway in macrophages and therefore may be a treatment for atherosclerosis.

Background As the mainstay treatment for coronary heart disease (CHD), aspirin alone is reported to be less effective than in combination when treating CHD. The aim of this analysis was to systematically evaluate the efficacy and safety of aspirin in combination with other drugs for the treatment of CHD, as well as its effect on the levels of inflammatory factors. Methods Electronic databases were searched from 2011 to 2021 and randomized controlled trials (RCTs) on aspirin in CHD patients were included in our study. Data was statistically analyzed using Stata 16.0 (StataCorp). Results A total of 13 RCTs were included, with a total of 1,442 patients. Compared with control group (aspirin alone) group, the response rate in the treatment group (aspirin in combination with other drugs) was significantly improved [odds ratio (OR) =5.11; 95% confidence interval (CI): 3.56-7.35], while the incidence of adverse reactions was markedly decreased (OR =0.36; 95% CI: 0.25-0.53). Before treatment, no significant differences were identified in the levels of inflammatory factors between the groups The inflammatory factors included C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). After treatment, CRP and TNF-α levels were significantly lower in both groups compared with those before treatment. However, there was no statistically significant difference in IL-6 levels after treatment between the groups. Discussion Aspirin is effective in the treatment of CHD, both alone and in combination. However, the latter has higher clinical efficacy and safety, and can significantly reduce the level of inflammatory factors in CHD patients.

Purpose: Sulfated galactofucan (SWZ-4), which was extracted from Sargassum thunbergii, has recently been reported to have anti-inflammatory and anti-cancer property. The present study aimed to evaluate if SWZ-4 could attenuate atherosclerosis in Apolipoprotein E-deficient (ApoE KO) mice by suppressing inflammatory response through TLR4/MyD88/NF-κB signaling pathway.Methods: Male ApoE KO mice were fed with high-fat diet for 16 weeks and intraperitoneally injected with SWZ-4. RAW246.7 cells were treated with lipopolysaccharide (LPS) and SWZ-4. Atherosclerotic lesions were measured by Sudan IV and Oil Red O staining. Serum lipid profiles, inflammatory cytokines, and mRNA and protein expression levels were evaluated.Results: SWZ-4 decreased serum TNF-α, IL-6 and IL-1 levels, but cannot improve blood lipid profiles. SWZ-4 downregulated the mRNA and protein expression of TLR4, MyD88 and phosphorylation of p65 and attenuated atherosclerosis in the ApoE KO mice (P < 0.01). In LPS-stimulated RAW 264.7 cells, SWZ-4 inhibited pro-inflammatory cytokines and the mRNA expression of TLR4, MyD88 and p65 and reduced the proteins expression of TLR4, MyD88 and the phosphorylation of p65 (P < 0.01).Conclusion: These results suggest that SWZ-4 exerts an anti-inflammatory effect in ApoE KO atherosclerosis mice via inhibiting TLR4/MyD88/NF-κB signaling pathway in macrophages, and may potentially serve as a treatment for atherosclerosis.

The mechanism of abdominal aortic aneurysm (AAA) has not been fully elucidated. In this study, we aimed to map the cellular heterogeneity, molecular alteration, and functional transformation of angiotensin (Ang) II-induced AAA in mice based on single-cell RNA sequencing (sc-RNA seq) technology. sc-RNA seq was performed on suprarenal abdominal aorta tissue from male

Background Treatment of coronary in-stent restenosis (ISR) remains challenging in contemporary clinical applications. Drug-coated balloon (DCB) angioplasty offers an effective treatment for ISR. Shenqi is a novel iopromide-based paclitaxel-coated balloon and its clinical safety, effectiveness and angiographic efficacy in patients with ISR have not been investigated. Methods A total of 216 subjects with the first occurrence of ISR at 11 investigational sites in China were randomly allocated in a 1:1 fashion to treatment with DCB SeQuent Please or Shenqi. Clinical follow-up was planned at 1, 6, 9 and 12 months, and angiographic follow-up was planned at 9 months. The study was powered for the primary endpoint of 9-month in-segment late loss. Results At 9-month follow-up, the in-segment late loss was 0.29 ± 0.43 mm with Shenqi versus 0.30 ± 0.46 mm with SeQuent Please, and the one-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of Shenqi compared with SeQuent Please (P = 0.002). In total, 12 patients developed target lesion failure (TLF) in the Shenqi group compared with 16 patients in the SeQuent Please group (10.91% versus 15.09%; P = 0.42) within 1 year. TLF was mainly driven by target lesion revascularization (9.09%) followed by target vessel-related myocardial infarction (1.82%) and cardiovascular death (0.91%) in the Shenqi group. Conclusions Shenqi DCB was noninferior to SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. Shenqi DCB may become an attractive alternative treatment for patients with coronary ISR, withholding the need for additional stent implantation.

Extracellular matrix metalloproteinase inducer (EMMPRIN) had been reported to be involved in the occurrence and development of coronary heart disease (CHD) in previous studies. This study aimed to investigate whether single nucleotide polymorphisms of EMMPRIN and matrix metalloproteinase-9 (MMP-9) contributed to the onset and severity of CHD. One thousand seventy patients suspected to have CHD were enrolled into the study. Each patient had undergone coronary angiogram, and the severity of coronary artery stenosis was assessed by Gensini score. Eight hundred twelve patients were confirmed to have CHD, while 258 patients were selected as non-CHD control. All patients were genotyped for five EMMPRIN polymorphisms (rs8259, rs28915400, rs4919859, rs6758, and rs8637) and one MMP-9 polymorphism (rs3918242) by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing. EMMPRIN polymorphism rs8259 and MMP-9 polymorphism rs3918242 were found to be associated with CHD (rs8259: AT vs. AA, adjusted odds ratio [OR] = 2.038, adjusted 95% confidence interval [CI] = 1.080-3.847

Background: Abdominal aortic aneurysm (AAA) is a severe form of blood vessel-related disease. Medial degeneration and inflammation are typical characteristic of AAA. Activated platelets release many pro-inflammatory cytokines and participate in the initial inflammatory response to various vascular diseases. Although there are some studies on the effects of APAs on AAA, it is yet unknown whether the new P2Y12 receptor inhibitor ticagrelor (T) can inhibit AAA. Herein, we explored the consequences of ticagrelor exposure on AAA progression and determined whether a combinational therapy, involving T and aspirin (A), exerts a stronger inhibitory effect in vivo. Methods: AAA was established in apolipoprotein E-deficient (ApoE-/-) mice via a 28-day administration of angiotensin II (Ang II). Next, the mice were arbitrarily separated into 5 groups: saline infusion alone (sham), Ang II infusion alone, Ang II infusion plus oral A (10 mg·kg −1 ·d −1), Ang II infusion plus oral T (120 mg.kg-1 .d-1), Ang II infusion plus combinational therapy with A (10 mg·kg −1 ·d −1) and T (120 mg.kg-1 .d-1). Results: The combined treatment markedly suppressed the Ang II-driven elevation of maximal aortic diameter, aneurysm formation (26.7% decrease, P

The study explored the role of platelet TGF-β1 from the perspective of inhibiting the excessive proliferation, migration and invasion of murine aortic vascular smooth muscle cells (MASMCs).The platelets were first extracted from C57BL/6 mice, and the TGF-β1 protein was obtained after the purification of protein. In vitro, the concentrations of angiotensin Ⅱ (Ang Ⅱ) and TGF-β1 for intervention were screened by testing the viability of MASMCs, followed by the analysis concerning the effects of platelets, Ang Ⅱ and TGF-β1 on the proliferation, migration, invasion, and the expressions of pathway-related proteins in MASMCs. In vivo, an Ang Ⅱ-induced mouse model was established. TGF-β1 was injected into the tail of mice as a therapeutic agent, and its action mechanism was further verified by the treatment of inhibitor SB505124. The results of the cell experiment were validated by evaluating the maximum diameter of abdominal aorta, the proportion of total weight, the changes of both pathology and the expressions of pathway-related proteins in the mice.0.5 ng/mL Ang Ⅱ and 15 ng/mL TGF-β1 were chosen for treatment. The following results of cell functional experiments and Western blot assay demonstrated that Ang Ⅱ promoted the proliferation, migration and invasion of MASMCs via regulating related pathways, the effects of which were evidently reversed by TGF-β1 and platelets. Consistent results were also observed in the animal experiments, where TGF-β1 effectively alleviated Ang Ⅱ-induced abdominal aortic injury in mice.TGF-β1 in platelets inhibits Ang Ⅱ-induced proliferation, migration and invasion of MASMCs.

Aim: The mechanism of abdominal aortic aneurysm (AAA) has not been fully elucidated. In this study, we aimed to map the cellular heterogeneity, molecular alteration, and functional transformation of angiotensin (Ang) II-induced AAA in mice based on single-cell RNA sequencing (sc-RNA seq) technology.Method: Single-cell RNA sequencing was performed on suprarenal abdominal aorta from male APOE-/- C57BL/6 mice of Ang II-induced AAA and shame models. Immunohistochemistry was used to determine the pathophysiological characteristics of AAA, and sc-RNA seq was used to determine the heterogeneity and phenotypic transformation of all cell types. A single-cell trajectory was performed to predict the differentiation of fibroblasts. Finally ligand–receptor analysis was used to evaluate intercellular communication between fibroblasts and smooth muscle cells.Results: More than 27,000 cells were isolated and 25 clusters representing 8 types of cells were identified, including fibroblasts, macrophages, endothelial cells, smooth muscle cells, T lymphocytes, B lymphocytes, granulocytes, and natural killer cells. During AAA progression, the function and phenotype of different type cells altered separately. The pro-inflammatory function of inflammatory cells was enhanced. The proliferation phenotype degreased while pro-inflammatory, regeneration and damage-related phenotypes increased in endothelial cells. Smooth muscle cells also transformed from contractile to secretory phenotype. The alterations of fibroblasts were the most conspicuous according sub-group clustering analysis. Single-cell trajectory revealed the critical reprogramming genes of fibroblasts mainly enriched in regulation of immune system. Finally, the ligand–receptor analysis confirmed that increases in secondary collagen synthesis led by fibroblasts were one of the most prominent characteristics of Ang II-induced AAA.Conclusion: Our study revealed the cellular heterogeneity of Ang II-induced AAA. Fibroblasts may play a central role in Ang II-induced AAA progression according multiple biological functions including immune regulation and extracellular matrix metabolic balance. Our study may provide us with a different perspective on the etiology and pathogenesis of AAA.

Inflammation is the primary cause of abdominal aortic aneurysm (AAA) formation and development. It has been reported that platelets protect against septic shock by inhibiting inflammation. However, it is unclear whether platelets protect AAA progress via suppressing inflammation.A mouse model of AAA was established by a daily administration of angiotensin II (Ang II, 1000 ng/kg/min) for 28-day. The AAA mice received 1 × 10Platelets infusion significantly suppressed the Ang II-driven elevation of aortic diameter, AAA formation (52.38% decrease, P 0.05), aortic expansion, elastic lamina destruction, and inflammatory response. In addition, MMP-2 and MMP-9 production were also reduced by platelets transfusion.For the first time, our study reported the beneficial effect of platelet transfusion in suppressing the Ang II-driven AAA progress in mice through the inhibition of inflammation.

Atherosclerosis (AS) is a cardiovascular disorder accompanied by endothelial dysfunction. Extensive evidence demonstrates the regulatory functions of long noncoding RNAs (lncRNAs) in cardiovascular disease, including AS. Here, the function of lncRNA small nucleolar RNA host gene 12 (SNHG12) in AS progression was investigated. A cell model of AS was established in human umbilical endothelial cells (HUVECs) using oxidative low-density lipoprotein (ox-LDL). CCK-8, flow cytometry, TUNEL, ELISA, and western blotting analyses were performed. Apolipoprotein E-deficient (apoE(−/−)) mice fed a Western diet were used as in vivo models of AS. RT-qPCR determined the levels of SNHG12, microRNA-218-5p (miR-218-5p) and insulin-like growth factor-II (IGF2). The molecular mechanisms were investigated using luciferase reporter and RNA pull-down assays. We found that SNHG12 and IGF2 expression levels were high and miR-218-5p expression levels were low in AS patients and ox-LDL-treated HUVECs. SNHG12 depletion attenuated ox-LDL-induced injury in HUVECs, whereas miR-218-5p suppression partially abated this effect. Moreover, IGF2 overexpression prevented the alleviative role of miR-218-5p in ox-LDL-treated HUVECs. SNHG12 upregulated IGF2 expression by sponging miR-218-5p. More importantly, SNHG12 increased proinflammatory cytokine production and augmented atherosclerotic lesions in vivo. Overall, SNHG12 promotes the development of AS by the miR-218-5p/IGF2 axis.

Background. Aortic dissection (AD) is a lethal vascular disease with high mortality and morbidity. Though AD clinical pathology is well understood, its molecular mechanisms remain unclear. Specifically, gene expression profiling helps illustrate the potential mechanism of aortic dissection in terms of gene regulation and its modification by risk factors. This study was aimed at identifying the genes and molecular mechanisms in aortic dissection through bioinformatics analysis. Method. Nine patients with AD and 10 healthy controls were enrolled. The gene expression in peripheral mononuclear cells was profiled through next-generation RNA sequencing. Analyses including differential expressed gene (DEG) via DEGseq, weighted gene coexpression network (WGCNA), and VisANT were performed to identify crucial genes associated with AD. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was also utilized to analyze Gene Ontology (GO). Results. DEG analysis revealed that 1,113 genes were associated with AD. Of these, 812 genes were markedly reduced, whereas 301 genes were highly expressed, in AD patients. DEGs were rich in certain categories such as MHC class II receptor activity, MHC class II protein complex, and immune response genes. Gene coexpression networks via WGCNA identified 3 gene hub modules, with one positively and 2 negatively correlated with AD, respectively. Specifically, module 37 was the most strongly positively correlated with AD with a correlation coefficient of 0.72. Within module 37, five hub genes (AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D) displayed high connectivity and may have clinical significance in the pathogenesis of AD. Conclusion. Our analysis provides the possible association of specific genes and gene modules for the involvement of the immune system in aortic dissection. AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D in module M37 were highly connected and strongly linked with AD, suggesting that these genes may help understand the pathogenesis of aortic dissection.

Background: The study aimed to investigate whether ligustrazine, a traditional Chinese medicine, could attenuate myocardial ischemia/reperfusion (I/R) injury and explore the potential mechanism.Methods: 32 Sprague-Dawley rats were divided equally into four groups: sham operation (S); (I/R); I/R + ligustrazine preconditioning (Lig); I/R + ligustrazine preconditioning + mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) (Lig + LND). Myocardial I/R model was established and ligustrazine was administered intraperitoneally 5 min prior to ischemia, LND was administered intraperitoneally 10 min prior to reperfusion. The infarct area (IA) was measured by Evans blue staining, where levels of Myocardial injury markers, malondialdehyde (MDA), superoxide dismutase (SOD), adenosine triphosphate (ATP) were detected. RT-PCR and Western Blot were adopted to measure the uncoupling protein 3 (UCP3) expression.Results: Compared to I/R group, the IA/area at risk (AAR) in Lig, and Lig + LND groups were significantly decreased, UCP3 levels of mRNA and protein were increased (P < 0.05). Compared to Lig group, the IA/AAR in Lig + LND group was significantly increased (P < 0.05). Ligustrazine pretreatment increased SOD, ATP activity, and decreased cardiac troponin I (cTnI), creatine kinase-muscle/brain (CK-MB), lactate dehydrogenase (LDH) and MDA activities. The effect of ligustrazine was reversed by LND.Conclusion: The present results indicated that ischemic preconditioning of ligustrazine might protect myocardium against I/R injury through upregulating UCP3 expression.

It remains obscure whether circulating aortic zinc (Zn) and copper (Cu) levels are associated with the progress of human abdominal aortic aneurysms (AAA). Therefore, we conducted a meta-analysis to explore this relationship. A literature search on circulating and aortic zinc and copper levels and AAA patients was conducted using online databases including PubMed, Embase, and Cochrane up to March 20, 2019. To compare Zn and Cu concentrations in AAA patients with those in aortic occlusive disease (AOD) patients or healthy aorta donors or healthy blood donors, pooled weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated. Subgroup analysis, sensitivity analysis, and meta-regression analysis were applied to explain the heterogeneity and evaluate the robustness of combined results. A total of 10 cross-sectional studies, including 252 cases and 304 controls, were used for meta-analysis. We found that circulating zinc and Zn/Cu ratio in AAA patients were significantly lower [WMD (95%CI): − 2.23 (− 4.10, − 0.36); − 0.18 (− 0.31, − 0.05), respectively] than those in non-AAA patients. Similarly, aneurysmal aorta had significantly lower zinc levels and Zn/Cu ratio [WMD (95%CI): − 9.22 (− 15.37, − 3.07); − 6.46 (− 10.14, − 2.77), respectively] than those in control group. No difference in circulating or aortic copper levels was noted between AAA patients and control group [WMD (95%CI): - 0.24 (- 2.09, 1.61); 0.30 (- 0.01, 0.61) , respectively]. Our meta-analysis suggests that zinc levels and Zn-Cu ratio, but not copper levels, may influence aneurysmal progress of AAA.

The present study aimed to further investigate the effects of high glucose on the function of circulating fibrocytes and its underlying mechanisms. The total peripheral blood mononuclear cells were obtained from normal glucose tolerance patients and type 2 diabetic mellitus patients. Circulating fibrocytes were stimulated with different glucose concentrations for different time periods (24, 48 and 72 h). Cell proliferation was determined by Cell Counting Kit-8 assay. The expression of connective tissue growth factor (CTGF) was detected by western blotting. The expression of COL-I was detected by flow cytometry. The apoptotic bodies of cells were detected by fluorescence microscopy after Hoechst33258 staining. The invasive and migration abilities of fibrocytes were detected by Transwell chamber assay. Secretion of stromal cell-derived factor 1 (SDF-1) was measured by ELISA. The circulating fibrocytes showed a typical spindle-shape and were double-positive for cluster of differentiation 45 (green) and COL-I (red). Compared with the 5.5 mmol/l glucose group, a high glucose concentration significantly promoted the proliferation of circulating fibrocytes and showed the most significant effects at 30 mmol/l after treatment for 48 h. AMD3100 showed no effects on the proliferation of circulating fibrocytes. Flow cytometry revealed that 30 mmol/l glucose significantly promoted the expression of COL-I vs. 5.5 mmol/l glucose group (P0.05). Western blotting revealed that the expression of CTGF was decreased significantly by AMD3100 pretreatment (P0.05). High glucose stimulated the expressions of CTGF and COL-I, and promoted migration of circulating fibrocytes via the CXC chemokine receptor 4/SDF-1 axis.

Acute myocardial infarction (AMI) is one of the most common and life-threatening cardiovascular diseases. However, the ability to diagnose AMI within 3 h is currently lacking. The present study aimed to identify the differentially expressed proteins of AMI within 3 h and to investigate novel biomarkers using isobaric tags for relative and absolute quantitation (ITRAQ) technology. A total of 30 beagle dogs were used for establishing the MI models successfully by injecting thrombin powder and a polyethylene microsphere suspension. Serum samples were collected prior to (0 h) and following MI (1, 2 and 3 h). ITRAQ-coupled liquid chromatography-mass spectrometry (LC-MS) technology was used to identify the differentially expressed proteins. The bioinformatics analysis selected several key proteins in the initiation of MI. Further analysis was performed using STRING software. Finally, western blot analysis was used to evaluate the results obtained from ITRAQ. In total, 28 proteins were upregulated and 23 were downregulated in the 1 h/0 h group, 28 proteins were upregulated and 26 were downregulated in the 2 h/0 h group, and 24 proteins were upregulated and 19 were downregulated in the 3 h/0 h group. The Gene Ontology (GO) annotation and functional enrichment analysis identified 19 key proteins. Protein-protein interactions (PPIs) were investigated using the STRING database. GO enrichment analysis revealed that a number of key proteins, including ATP synthase F1 subunit β (ATP5B), cytochrome c oxidase subunit 2 and cytochrome c, were components of the electron transport chain and were involved in energy metabolism. The western blot analysis demonstrated that the expression of ATP5B decreased significantly at all three time points (P

Cardiac fibrosis is closely associated with various heart diseases and is an important pathological feature of cardiac remodeling. However, detailed mechanisms underlying cardiac fibrosis remain largely unknown. Long noncoding RNAs (lncRNAs) are reported to serve significant roles in the development of cardiac fibrosis. The present study aimed to identify the role of a novel lncRNA, homeobox A11 antisense (HOXA11‑AS), in cardiac fibrosis. Overexpression of HOXA11‑AS in mouse cardiac fibroblasts (CFs) increased the expression of transforming growth factor β1 (TGFβ1) and its downstream molecules, while knockdown of HOXA11‑AS inhibited the TGFβ1 signaling pathway. Furthermore, as determined by colony formation and MTT assays, HOXA11‑AS overexpression promoted colony formation and viability in mouse CFs, while HOXA11‑AS knockdown had the opposite effect. In addition, overexpression of HOXA11‑AS increased cell migration and invasion in the Transwell assays, whereas expression knockdown decreased the metastatic ability of cells. In order to explore the detailed mechanism, co‑transfection of HOXA11‑AS expression plasmid and siTGFβ1 into CFs resulted in increased cell proliferative rate and cell metastasis through the TGFβ1 signaling pathway. Taken together, the present study suggested that the lncRNA HOXA11‑AS may be a potential therapeutic target against cardiac fibrosis, and provided a novel insight into the diagnosis and treatment of clinical cardiac fibrosis.

Background This study assessed the effect of ibandronate (IBN), a farnesyl pyrophosphate synthase (FPPS) inhibitor, on vascular remodeling in diabetic rats. Methods A rat model of diabetes was induced by a high-fat and high-sugar diet combined with a small dose of streptozotocin. The diabetic rats received 5 µg/kg of ibandronate solution or normal saline subcutaneously every morning for 16 weeks. The morphology of the thoracic aorta was assessed by hematoxylin and eosin and Masson's trichrome staining techniques. Gene expression levels of connective tissue growth factor (CTGF) and FPPS were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. CTGF and FPPS protein levels were determined by Western blotting analysis. Results Rats with diabetes mellitus showed moderate hyperglycemia, insulin resistance, hyperlipidemia and thoracic aortic fibrosis. FPPS was significantly upregulated in the thoracic aorta from diabetic animals. Interestingly, IBN treatment for 16 weeks alleviated the diabetes-induced histopathologic changes in the thoracic aortic wall and reduced CTGF protein and mRNA levels. Conclusions These findings provided evidence that FPPS is involved in thoracic aortic fibrosis in diabetic rats. Meanwhile, IBN could alleviate vascular remodeling in diabetic animals.

Background The RESOLUTE-DIABETES CHINA study was specifically designed to investigate the safety and efficacy of Resolute zotarolimus-eluting stents (ZES; Medtronic, Santa Rosa, CA, USA) in the treatment of diabetic coronary lesions in the Chinese population. Methods In all, 945 patients with de novo native coronary lesions and type 2 diabetes mellitus were recruited at 32 cardiac centers across the Chinese mainland and were implanted with Resolute ZES. The primary endpoint was target vessel failure (TVF); secondary endpoints were clinical outcomes, namely all-cause death, stroke, bleeding, target lesion revascularization (TLR), target vessel revascularization (TVR), non-TVR, and stent thrombosis (ST). The follow-up period for all endpoints was 12 months after the procedure. Results In all, 933 patients (98.73%) had clinical follow-up at 12 months. The rate of TVF was 11.60%, whereas the rate of occurrence of secondary endpoints was 5.47%, with four patients (0.43%) having subacute or late ST. There were no significant differences in TVF rates comparing patients with different HbA1c levels or receiving different glucose control treatments (all P > 0.05). Patients with multivessel lesions had higher TVF rates (95% confidence intervals) than those with single-vessel lesions (16.76% [12.10%-22.97%) vs 9.72% [7.79%-12.11%], respectively; P = 0.006). There were no significant differences in TVF rates in patients with or without small vessels, bifurcated lesions, or chronic total occlusions (all P > 0.05). [Correction added on 17 January 2019, after first online publication: in the second sentence of Results section, "TLF" was changed to "TVF".]. Conclusions Resolute ZES may perform well in the Chinese diabetic population, especially in those with poor glucose control, complex lesions, and certain unfavorable clinical features. Further studies are needed to determine why ZES perform well in this population.

Background The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. Methods The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China. Chinese patients with coronary heart disease and impaired glucose tolerance were randomly assigned (1:1), in blocks by site, by a centralised computer system to receive oral acarbose (50 mg three times a day) or matched placebo, which was added to standardised cardiovascular secondary prevention therapy. All study staff and patients were masked to treatment group allocation. The primary outcome was a five-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospital admission for unstable angina, and hospital admission for heart failure, analysed in the intention-to-treat population (all participants randomly assigned to treatment who provided written informed consent). The secondary outcomes were a three-point composite outcome (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, development of diabetes, and development of impaired renal function. The safety population comprised all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513. Findings Between March 20, 2009, and Oct 23, 2015, 6522 patients were randomly assigned and included in the intention-to-treat population, 3272 assigned to acarbose and 3250 to placebo. Patients were followed up for a median of 5·0 years (IQR 3·4–6·0) in both groups. The primary five-point composite outcome occurred in 470 (14%; 3·33 per 100 person-years) of 3272 acarbose group participants and in 479 (15%; 3·41 per 100 person-years) of 3250 placebo group participants (hazard ratio 0·98; 95% CI 0·86–1·11, p=0·73). No significant differences were seen between treatment groups for the secondary three-point composite outcome, death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, or impaired renal function. Diabetes developed less frequently in the acarbose group (436 [13%] of 3272; 3·17 per 100 person-years) compared with the placebo group (513 [16%] of 3250; 3·84 per 100 person-years; rate ratio 0·82, 95% CI 0·71–0·94, p=0·005). Gastrointestinal disorders were the most common adverse event associated with drug discontinuation or dose changes (215 [7%] of 3263 patients in the acarbose group vs 150 [5%] of 3241 in the placebo group [p=0·0007]; safety population). Numbers of non-cardiovascular deaths (71 [2%] of 3272 vs 56 [2%] of 3250, p=0·19) and cancer deaths (ten [ Interpretation In Chinese patients with coronary heart disease and impaired glucose tolerance, acarbose did not reduce the risk of major adverse cardiovascular events, but did reduce the incidence of diabetes.

Recent evidence indicates a pivotal role for fetuin B, one of the cystatin superfamily of cysteine protease inhibitors, in the pathogenesis of metabolic diseases. This study investigated whether serum fetuin B levels are associated with the presence of coronary artery disease. Serum fetuin B levels were assessed in 87 patients with coronary artery disease (41 with acute coronary syndromes and 46 with stable angina pectoris) and 87 healthy controls using an enzyme-linked immunosorbent assay. The association of serum fetuin B levels with cardiac risk factors was analyzed. Serum fetuin B levels were significantly higher in patients with coronary artery disease than those in healthy controls (90.7 ± 32.1 vs. 110.0 ± 32.7 μg/ml, P

Data are limited regarding the adequacy of risk factor control and adherence to recommended therapies among adults with heart failure (HF). We evaluated the adequacy of risk factor control and adherence to recommended pharmacologic therapies among non-institutionalized US adults with HF. We examined data from US adults aged 18 years and older with a self-reported history of HF from the US National Health and Nutrition Examination Survey 2007–2008 and 2009–2010. We estimated the proportions of subjects who reported recommended lifestyle modification and medications and were at target levels of blood pressure, low-density lipoprotein cholesterol (LDL-C), and hemoglobin A1c. Among 371 subjects with HF in our study, 73.7 % were non-smokers, while only 69.1, 51.9, and 56.2 % were at goal for blood pressure, LDL-C, and hemoglobin A1c (if diabetic), respectively; only 9.0 % were at goal for all measures. The proportions of non-smokers were lower in males (p

Persons with known coronary heart disease (CHD) are at a greater risk of subsequent events. The current guidelines for secondary prevention have focused on lifestyle modifications, risk factor control, and drug therapy. However, current data lack information on the United States population and its adherence to these guidelines. Using data from the National Health and Nutrition Examination Survey from 2007 to 2010, we identified those with CHD and assessed the adequacy of their adherence to the current guidelines for secondary prevention. Of 759 subjects with CHD (weighted to 12.7 million), the use of recommended therapies was 55%, 45%, and 62% for β blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and lipid-lowering agents, respectively (24% for all), with adherence lower in women than in men and in blacks and Hispanics than in whites. The nonsmoking status and control of blood pressure, low-density lipoprotein cholesterol, and, for those with diabetes, glycated hemoglobin was 73%, 67%, 59%, 60%, respectively (14% for all). Also, 17%, 70%, and 7% were at the recommended levels for physical activity, alcohol consumption, and sodium intake, respectively. Moreover, only 20% and 29% were at the recommended body mass index and waist circumference targets, respectively. Those with metabolic syndrome and diabetes were more likely to have ≥2 risk factors uncontrolled, despite being more likely to be receiving recommended therapies. A significant gap still exists between the secondary prevention guidelines and their adherence and control of CHD risk factors among United States adults. In conclusion, greater efforts are needed to ensure adherence to all aspects of secondary prevention guidelines to optimize the prognosis in subjects with CHD.

Background and Objective: Aortic diameter is a critical parameter for the diagnosis of aortic aneurysm. In non-aneurysm patients, a large infrarenal aortic diameter are also a risk for all-cause mortality. Additionally, aortic dimension is associated with several risk factors of coronary artery disease; the measure of subclinical disease; a predictor of incident congestive heart failure; stroke risk; and all-cause and cardiovascular disease mortality. The purpose of this study was to explore the risk factors and potential alternative pathogenic mechanisms of aortic dilatation. Methods and Results: Five hundred and twenty patients with clinically evident arterial disease or cardiovascular risk factors were prospectively recruited. Comprehensive transthoracic M-mode, 2-dimensional, and Doppler echocardiographic studies were performed using commercially and clinical diagnostic ultrasonography technique. The aortic dimensions were assessed at end-diastole at the different levels: (1) the annulus, (2) the mid-point of the sinuses of Valsalva, (3) the sinotubular junction, (4) the ascending aorta at the level of its largest diameter, (5) the transverse arch, (6) the descending aorta posterior to the left atrium, and (7) the abdominal aorta just distal to the origin of the renal arteries. The relationships of aortic dimensions with clinical characteristics were assessed by linear multiple regression analysis. Variables analyzed included common cardiovascular risk factors, co-morbidities, lipid profile, hematological parameters. Age and diastolic blood pressure were positively associated with the diameters of arch, descending, ascending and abdominal aorta. In contrast, female gender and hypertension were negatively associated with the diameters of arch, descending, ascending and abdominal aorta. The presence of coronary arterial disease were positively associated with arch diameter, whereas High-density lipoprotein cholesterol levels were positively associated with the diameters of ascending, descending and abdominal aorta. Effects from other factors varied among aortic segments. Conclusion: Aortic segmental diameters are influenced by both common and segment-specific factors.