Background: The association of soy product consumption with the relative risk of cardiovascular disease remains controversial. This meta-analysis aimed at investigating whether an association exists between soy consumption and the risk of stroke and coronary heart disease (CHD) in observational studies. Methods: A systematic search of the PubMed and EMBASE databases was performed for case-control and cohort studies that assessed soy consumption and the risk of stroke and CHD. Summary relative risks (SRRs) and 95% CIs were combined by using a random-effects model. Results: Of a total of 1,266 abstracts, 5 prospective cohort and 6 case-control studies met our inclusion criteria, and comprised 4,954 stroke and 7,616 CHD events. Based on the high vs. low analyses, combining cohort studies showed no association between soy intake and risk of stroke (SRR 0.92; 95% CI 0.70-1.10; P_{heterogeneity} = 0.236; I² = 29.4%) or CHD (SRR 0.97; 95% CI 0.74-1.27; P_{heterogeneity} = 0.020; I² = 62.7%), although a significantly inverse association between soy intake and the risk of stroke (SRR 0.54; 95% CI 0.34-0.87; P_{heterogeneity} = 0.001; I² = 79.3%) and CHD (SRR 0.66; 95% CI 0.56-0.77; P_{heterogeneity} = 0.421; I² = 0) was observed in case-control studies. No association between soy isoflavone intake and the risk of stroke and CHD was identified. Conclusion: There was limited evidence to indicate that soy consumption was inversely associated with the risk of stroke and CHD, although further studies, with prospective designs that use validated questionnaires and control for important confounders, are warranted.

Abdominal aortic aneurysm (AAA) is characterized by aorta dilation due to wall degeneration, which mostly occurs in elderly males. Vascular aging is implicated in degenerative vascular pathologies, including AAA. Cyclic nucleotide phosphodiesterases, by hydrolyzing cyclic nucleotides, play critical roles in regulating vascular structure remodeling and function. Cyclic nucleotide phosphodiesterase 1C (PDE1C) expression is induced in dedifferentiated and aging vascular smooth muscle cells (SMCs), while little is known about the role of PDE1C in aneurysm. We observed that PDE1C was not expressed in normal aorta but highly induced in SMC-like cells in human and murine AAA. In mouse AAA models induced by Angiotensin II or periaortic elastase, PDE1C deficiency significantly decreased AAA incidence, aortic dilation, and elastin degradation, which supported a causative role of PDE1C in AAA development in vivo. Pharmacological inhibition of PDE1C also significantly suppressed preestablished AAA. We showed that PDE1C depletion antagonized SMC senescence in vitro and/or in vivo, as assessed by multiple senescence biomarkers, including senescence-associated β-galactosidase activity, γ-H2AX foci number, and p21 protein level. Interestingly, the role of PDE1C in SMC senescence in vitro and in vivo was dependent on Sirtuin 1 (SIRT1). Mechanistic studies further showed that cAMP derived from PDE1C inhibition stimulated SIRT1 activation, likely through a direct interaction between cAMP and SIRT1, which leads to subsequent up-regulation of SIRT1 expression. Our findings provide evidence that PDE1C elevation links SMC senescence to AAA development in both experimental animal models and human AAA, suggesting therapeutical significance of PDE1C as a potential target against aortic aneurysms.

Background Atherosclerosis is an aging-related disease, partly attributed to telomerase dysfunction. This study aims to investigate whether telomere dysfunction-related vascular aging is involved in the protection mechanism of melatonin (MLT) in atherosclerosis. Methods Young and aged ApoE −/− mice were used to establish atherosclerotic mice model. H&E staining and immunofluorescence assay were performed to detect endothelial cell injury and apoptosis. Inflammatory cytokines and oxidative stress-related factors were determined using corresponding commercial assay kits. Telomerase activity was detected by TRAP assay, and SA-β-gal staining was conducted to evaluate cellular senescence. HUVECs were treated with H 2 O 2 for 1 h to induce senescence. Western blot was performed to measure protein expression. Results An obvious vascular endothelial injury, reflected by excessive production of inflammatory cytokines, elevated ROS, MDA and SOD levels, and more apoptotic endothelial cells, was found in atherosclerotic mice, especially in aged mice, which were then greatly suppressed by MLT. In addition, telomere dysfunction and senescence occurred in atherosclerosis, especially in aged mice, while MLT significantly alleviated the conditions. CYP1A1, one of the targeted genes of MLT, was verified to be upregulated in atherosclerotic mice but downregulated by MLT. Furthermore, H 2 O 2 induced a senescence model in HUVECs, which was accompanied with a remarkably increased cell viability loss and apoptosis rate, and a downregulated telomerase activity of HUVECs, and this phenomenon was strengthened by RHPS4, an inhibitor of telomerase activity. However, MLT could partly abolish these changes in H 2 O 2 - and RHPS4-treated HUVECs, demonstrating that MLT alleviated vascular endothelial injury by regulating senescence and telomerase activity. Conclusions Collectively, this study provided evidence for the protective role of MLT in atherosclerosis through regulating telomere dysfunction-related vascular aging.

Dendrobine has been reported to reduce blood lipid levels and apoptosis. The present study was designed to observe the effect of dendrobine in a model of ERS using vascular endothelial cells and to reveal the biological mechanisms and pathways responsible for the therapeutic effects of dendrobine on AS. Human umbilical vein endothelial cells (HUVECs) were pre-treated with various concentrations of dendrobine, followed by treatment with tunicamycin (TM) for the establishment of the cell models of ERS. The proliferation and apoptosis of HUVECs were detected by bromodeoxyuridine staining and flow cytometry, respectively. The target binding association was verified through dual luciferase reporter assay. It was found that TM treatment resulted in a low expression of miR-381-3p. Dendrobine treatment not only promoted the proliferation, but also inhibited the apoptosis of HUVECs induced by TM. The reduced expression of 78-kDa glucoseregulated protein, inositol-requiring enzyme 1, caspase-4, C/EBP homologous protein and caspase-3 was also observed following treatment with dendrobine. Dendrobine reduced the apoptosis of endothelial cells in the model of ERS by increasing miR-381-3p expression, and partially restored the cell proliferation level. This effect was significantly reduced after the expression of miR-381-3p was blocked. On the whole, the present study demonstrated that dendrobine upregulated miR-381-3p expression to inhibit apoptosis induced by ERS in HUVECs and this process was found to be mediated by caspase-4. The findings of the present study may provide new insight into the causes of endothelial cell apoptosis during AS and reveal the potent therapeutic effects of dendrobine in AS.

Background Low testosterone levels have been associated with coronary heart disease (CHD) morbidity and mortality in men, but the influence of hormones in postmenopausal women is unclear. This meta-analysis aimed to examine whether there is an association between endogenous sex hormones and CHD risk in postmenopausal women. Methods A systematic search of the PubMed and EMBASE databases from 1966 to 30 November 2016 was performed for prospective studies that reported an association between endogenous sex hormones and CHD in postmenopausal women. Summary relative risks (RRs) and 95% confidence intervals (CIs) were combined by using a random-effects model. Results A total of 13 publications (12 studies, including six prospective cohort and six nested case-control studies) were included. The summary RRs for CHD were 1.01 (95% CI 0.77-1.31) comparing the highest versus lowest tertile of total testosterone, with evidence of high heterogeneity ( I= 80.7%). In subgroup and meta-regression analyses, none of the variables were identified as contributing to significant heterogeneity. Based on a comparison of the highest versus lowest tertile models, the summary RRs (95% CIs) for CHD were 0.88 (0.63-1.23, I= 48.7%) for free testosterone, 1.16 (0.82-1.63, I= 47.8%) for estradiol, 0.98 (0.90-1.07, I= 3.2%) for sex hormone-binding globulin and 1.19 (0.89-1.58, I= 0) for dehydroepiandrosterone. Conclusion There is limited evidence to suggest that endogenous levels of sex hormones are not significantly associated with CHD risk in postmenopausal women.

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Atherosclerosis is the most common cause of cardiovascular disease and is accompanied by high mortality rates and a poor prognosis. Semaphorin 7A (Sema7A) and its receptor β1 integrin have been reported to participate in the development of atherosclerosis. However, the role of Sema7A and β1 integrin in endothelial cell injury and endothelial-to-mesenchymal transition (EMT) in atherosclerosis remains undetermined, to the best of our knowledge. The mRNA and protein expression levels of Sema7A and β1 integrin in HUVECs were analyzed using reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses, respectively. HUVECs were induced with 50 µg/ml oxidized low-density lipoprotein (ox-LDL) to establish an atherosclerosis cell model. Cell viability was measured using Cell Counting Kit-8 assay and the production of IL-1β, IL-6 and C-C motif chemokine ligand 2 was determined using ELISA. The expression levels of cell adhesion factors, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 were analyzed using RT-qPCR and western blot analyses. Cell apoptosis was detected using flow cytometry and western blotting. The levels of EMT-related markers were evaluated using RT-qPCR, western blotting and immunofluorescence staining. The results of the present study revealed that the expression levels of Sema7A and β1 integrin were significantly upregulated in ox-LDL-treated HUVECs. Treatment with ox-LDL significantly decreased cell viability, and increased the levels of inflammatory and adhesion factors, the cell apoptotic rate and the expression levels of EMT-related proteins. Knockdown of Sema7A reversed the ox-LDL-induced inflammatory responses and EMT, while the overexpression of β1 integrin reversed the Sema7A-mediated inhibitory effects on ox-LDL-treated HUVECs. In conclusion, the findings of the present study indicated that Sema7A and β1 integrin may play significant roles in atherosclerosis by mediating endothelial cell injury and EMT progression.

Dendrobine has potential advantages in suppressing atherosclerosis (AS). FK506‐binding protein 1A (FKBP1A) is implicated in the regulation of autophagy, inflammation, and apoptosis. To reveal the mechanism by which dendrobine inhibits AS by modulating autophagy, oxidative stress, apoptosis, and senescence. An in vitro AS cell model was induced by culturing human umbilical vein endothelial cells (HUVECs) with oxidized low‐density lipoprotein (ox‐LDL). The cells were treated with dendrobine alone or in combination with short hairpin RNA (shRNA) targeting FKBP1A or together with 3‐methyladenine (3MA), an autophagy inhibitor. Inflammatory cytokines levels tumor necrosis factor‐α, interleukin‐6 (IL‐6), and IL‐1β were analyzed and oxidative stress levels were detected by the analysis of reactive oxygen species, malondialdehyde, and superoxide dismutase levels, followed by the analysis of apoptosis levels through terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Cell senescence was evaluated by senescence‐associated β‐galactosidase and light chain 3 (LC3) levels were detected by immunofluorescence (IF) staining. The targeting relationship of dendrobine and FKBP1A was predicted by SwissTarget, PyMol, Autodock, and Open Babel software. Dendrobine reduced the levels of proinflammation factors, oxidative stress levels, apoptosis levels, and senescence phenotype in ox‐LDL‐induced HUVECs. Besides, cell viability has an opposite change. Furthermore, there was an increase in LC3 IF tensity, and LC3‐II/I and Beclin1 expressions, and a decrease in p62 expression. However, these effects of dendrobine could be markedly destroyed by shRNA silencing FKBP1A and 3MA. Dendrobine can suppress inflammatory responses, oxidative stress, apoptosis, and senescence via FKBP1A‐involved autophagy ox‐LDL‐treated HUVECs.