Sclerostin, as a bone-derived secreted glycoprotein, is a suppressor of Wnt signaling pathway. Recently, adverse cardiovascular events in the treatment of osteoporosis with sclerostin inhibitors have raised concerns about the association of sclerostin with atherosclerotic heart disease. Whether the role of sclerostin in atherosclerotic heart disease is harmful or beneficial is not clear. This article reviews the progress of the mechanisms of sclerostin in vascular calcification and atherosclerotic heart disease, focusing on the relationship between sclerostin and vascular calcification, the impact of its concentration changes on atherosclerotic heart disease, and the effect of sclerostin inhibitor on cardiovascular events.
Objective To systematically review the correlation between obstructive sleep apnea syndrome (OSAS) and the incidence of carotid atherosclerosis. Methods PubMed, EMbase, CNKI, WanFang Data, CBM, and VIP databases were electronically searched to collect studies on the correlation between OSAS and carotid atherosclerosis and carotid intima-media thickness (CIMT) from inception to August 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using Stata 16.0 software and RevMan 5.3 software. Results A total of 32 studies, including 2 915 patients were included. The results of the meta-analysis showed a higher incidence of carotid atherosclerotic plaque in OSAS patients than in the control group (OR=5.56, 95%CI 0.27 to 8.38, P<0.000 01); subgroup analysis revealed that, compared with the control group, patients who were male (OR=5.38, 95%CI 2.79 to 10.38, P<0.000 01) or had mild-to-moderate OSAS (OR=3.9, 95%CI 1.66 to 9.15, P=0.002) or severe OSAS (OR=19.86, 95%CI 6.49 to 60.82, P<0.000 01) had a higher risk of carotid atherosclerosis. The CIMT of the OSAS group was significantly higher than that of the control group (SMD=1.24, 95%CI 0.97 to 1.51, P<0.000 01). There was a positive correlation between the apnea hypopnea index (AHI) and CIMT in OSAS patients (r=0.52, 95%CI 0.44 to 0.60, <0.000 1), and the CIMT increased with OSAS severity. Conclusion OSAS is associated with a high incidence of carotid atherosclerotic plaque that is highly correlated with CIMT, which increases with an increase in the AHI. These findings are required to be verified in prospective high-quality studies to overcome the limitations of quantity and quality of studies included in this systematic review.
Atherosclerotic plaque rupture is the main cause of many cardiovascular diseases, and biomechanical factors play an important role in the process of plaque rupture. In the study of plaque biomechanics, there are relatively few studies based on fatigue fracture failure theory, and most of them mainly focus on the whole fatigue propagation process from crack initiation to plaque rupture, while there are few studies on the influence of crack on plaque rupture at a certain time in the process of fatigue propagation. In this paper, a two-dimensional plaque model with crack was established. Based on the theory of fracture mechanics and combined with the finite element numerical simulation method, the stress intensity factor (SIF) and related influencing factors at the crack tip in the plaque were studied. The SIF was used to measure the influence of crack on plaque rupture. The results show that the existence of crack can lead to local stress concentration, which increases the risk of plaque rupture. The SIF at the crack tip in the plaque was positively correlated with blood pressure, but negatively correlated with fibrous cap thickness and lipid pool stiffness. The effect of the thickness and angle of lipid pool on the SIF at the crack tip in the plaque was less than 4%, which could be ignored. This study provides a theoretical basis for the risk assessment of plaque rupture with cracks.
ObjectiveTo explore the risk factors affecting occurrence of arteriosclerosis obliterans (ASO) for patients with type 2 diabetes mellitus (T2DM) and to develop a nomogram predictive model using these risk factors. MethodsA case-control study was conducted. The patients with T2DM accompanied with ASO and those with T2DM alone, admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2017 to December 2022, were retrospectively collected according to the inclusion and exclusion criteria. The basic characteristics, blood, thyroid hormones, and other relevant indicators of the paitents in two groups were compared. The multivariate logistic regression analysis was used to identify the risk factors for the occurrence of ASO in the patients with T2DM, and then a nomogram predictive model was developed. ResultsThere were 119 patients with T2DM alone and 114 patients with T2DM accompanied with lower extremity ASO in this study. The significant differences were observed between the two groups in terms of smoking history, white blood cell count, neutrophil count, lymphocyte count, platelet count, systemic immune-inflammation index, systemic inflammatory response index (SIRI), high-density lipoprotein cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein α (Apoα), serum cystatin C, free-triiodothyronine (FT3), total triiodothyronine, FT3/total triiodothyronine ratio, fibrinogen (Fib), fibrinogen degradation products, and plasma D-dimer (P<0.05). Further the results of the multivariate logistic regression analysis revealed that the history of smoking, increased Fib level and SIRI value increased the probabilities of ASO occurrence in the patients with T2DM [OR (95%CI)=2.921 (1.023, 4.227), P=0.003; OR (95%CI)=2.641 (1.810, 4.327), P<0.001; OR (95%CI)=1.020 (1.004, 1.044), P=0.018], whereas higher levels of ApoA1 and FT3 were associated with reduced probabilities of ASO occurrence in the patients with T2DM [OR (95%CI)=0.231 (0.054, 0.782), P=0.021; OR (95%CI)=0.503 (0.352, 0.809), P=0.002]. The nomogram predictive model based on these factors demonstrated a good discrimination for predicting the ASO occurrence in the T2DM patients [area under the receiver operating characteristic curve (95%CI)=0.788 (0.730, 0.846)]. The predicted curve closely matched the ideal curve (Hosmer-Lemeshow goodness-of-fit test, χ2=5.952, P=0.653). The clinical decision analysis curve showed that the clinical net benefit of intervention based on the nomogram model was higher within a threshold probability range of 0.18 to 0.80 compared to no intervention or universal intervention. ConclusionsThe analysis results indicate that T2DM patients with a smoking history, elevated Fib level and SIRI value, as well as decreased ApoA1 and FT3 levels should be closely monitored for ASO risk. The nomogram predictive model based on these features has a good discriminatory power for ASO occurrence in T2DM patients, though its value warrants further investigation.
Cardiovascular disease is a severe threat to human health and life. Among many risk factors of cardiovascular disease, genetic or gene-based ones are drawing more and more attention in recent years. Accumulated evidence has demonstrated that the loss or mutation of ataxia telangiectasia mutated (ATM) gene can result in DNA damage repair dysfunctions, telomere shortening, decreased antioxidant capacity, insulin resistance, increased lipid levels, etc., and thus can promote the occurrence of cardiovascular risk factors, such as aging, atherosclerosis and metabolic syndrome. In this review, we discusses the possible mechanisms between ATM gene and cardiovascular risk factors, which could be helpful to the related research and clinical application.
ObjectiveTo compare mid-to long-term outcomes of selective coronary venous bypass grafting (SCVBG) using internal mammary artery (IMA) grafts and great saphenous vein (GSV) grafts for surgical treatment of diffuse right coronary artery atherosclerosis. MethodsWe retrospectively analyzed clinical data of 75 patients undergoing SCVBG in Beijing Anzhen Hospital from January 2003 to December 2012. GSV was used as grafts for SCVBG in 54 patients (GSV group), and IMA was used as grafts for SCVBG in 21 patients (IMA group). All the patients were followed up in November 2013. Their survival condition, recent relapse rate of angina, recent echocardiographic results and coronary CT angiography (CTA) were analyzed. ResultsOverall survival rate of IMA group was slightly higher than that of GSV group (100.0% vs. 83.3%), but survival curves showed no statistical difference in survival rate between the 2 groups (P=0.055). Coronary CTA showed significant blockage in GSV grafts and middle cardiac vein in patients in GSV group (n=39), while IMA grafts and middle cardiac vein in patients in IMA group (n=18) were mostly visible and patent (P < 0.001). Left ventricular ejection fraction (LVEF) of the 2 groups were significantly higher than preoperative values, but there was no statistical difference between the 2 groups. ConclusionCompared with SCVBG using GSV, SCVBG using IMA can significantly improve mid-to long-term patency of the grafts and middle cardiac vein, and is an efficacious procedure for diffuse right coronary artery atherosclerosis.
Atherosclerosis is a complex disease characterized by lipid accumulation in the vascular wall and influenced by multiple genetic and environmental factors. To understand the mechanisms of molecular regulation related to atherosclerosis better, a protein interaction network was constructed in the present study. Genes were collected in nucleotide database and interactions were downloaded from Biomolecular Object Network Database (BOND). The interactional data were imported into the software Cytoscape to construct the interaction network, and then the degree characteristics of the network were analyzed for Hub proteins. Statistical significance pathways and diseases were figured out by inputting Hub proteins to KOBAS2.0. The complete pathway network related to atherosclerosis was constructed. The results identified a series of key genes related to atherosclerosis, which would be the potential promising drug targets for effective prevention.
ObjectiveTo explore the association of elongase of very long chain fatty acids family member 6 (ELOVL6) gene with increased risk of large-artery atherosclerosis stroke (LAA) in Han Chinese population in Chengdu.MethodsHan Chinese populations in Chengdu, Sichuan were chosen for this study using the case-control design between January 2015 and December 2017. The genotypes and haplotypes of six single nucleotides polymorphisms (SNPs) of ELOVL6 gene (rs3813825, rs17041272, rs4141123, rs9997926, rs6824447, and rs12504538) were analyzed in different genetic models in entire samples, and gene-enviromental interaction analyses were also carried out to get an insight of the risk factors for LAA. At the same time, we also analyzed the gene expression profile in peripheral blood mononuclear cells between groups.ResultsA total of 240 LAA cases and 211 healthy controls were enrolled in this study. All the enrolled subjects presented CC genotype of rs9997926, while the other five SNPs (rs3813825, rs17041272, rs4141123, rs6824447, and rs12504538) were genotyped successfully in all the enrolled subjects. rs17041272 polymorphism and TGTTG haplotype were significantly associated with LAA risk in studied population [CC/(CG+GG): odds ratio (OR)=0.640, 95% confidence interval (CI) (0.423, 0.968), P=0.034; TGTTG: OR=1.776, 95%CI (1.069, 2.951), P=0.024], and the interaction among rs17041272, rs6824447 SNPs and dyslipidemia increased susceptibility to LAA [OR=2.737, 95%CI (1.715, 4.368), P<0.001]. The ELOVL6 gene expression level was higher in LAA subjects (t=−3.167, P=0.003).ConclusionsELOVL6 gene is associated with LAA risk in Han nationality of Chinese population in Chengdu, and the interaction of gene-environmental risk factors could be of great importance in pathophysiology of LAA.
Fibroblast growth factor 21 (FGF21) is a multi-effect endocrine factor, mainly secreted in liver and adipose tissue, with the properties of lipid-lowering, anti-inflammatory, anti-oxidant and anti-atherosclerosis. Recent studies found that FGF21 can induce protective effect in cardiovascular disease, and plasma FGF21 levels in patients with disease cardiovascular are elevated. These studies have suggested the use of FGF21 as a biomarker for subclinical atherosclerosis and its potential role in the treatment of established atherosclerotic cardiovascular disease. This article will review the recent advances in the anti-atherosclerosis effect of FGF21.
ObjectiveTo explore the differential expression of Sirtuin1 (SIRT1) in type A aortic dissection at diverse ages.MethodsThe expression of SIRT1 and monocyte chemoattractant protein-1 (MCP-1) in aortic tissue of the patients with type A aortic dissection (an aortic dissection group) and coronary heart disease (a control group) from 2019 to 2020 in the First Hospital of China Medical University was analyzed. In each group, the patients were divided into 3 subgroups according to the age (a younger subgroup, <45 years; a middle age subgroup, 45-60 years; an elderly subgroup, >60 years). The quantitative real-time PCR, Western blotting and immunochemical stainning were used to detect the mRNA or protein expression of SIRT1 and MCP-1. ResultsA total of 60 patients were included in each group, including 79 males and 41 females. There were 20 patients in the yonger, middle age and elderly subgroups for the two groups, respectively. Compared with the control group, the expression of SIRT1 mRNA decreased in the aortic dissection group (the younger subgroup: 4.54±1.52 vs. 8.78±2.57; the middle age group: 2.70±1.50 vs. 5.74±1.07; the elderly group: 1.41±1.33 vs. 3.09±1.14, P<0.001). Meanwhile, SIRT1 mRNA in the aortic dissection group declined with age (P<0.01). Compared with the control group, SIRT1 protein expression decreased significantly in the aortic dissection group (the younger group: 0.64±0.18 vs. 1.18±0.47; the middle age group: 0.43±0.26 vs. 0.69±0.32; the elderly group: 0.31±0.24 vs. 0.45±0.29, P<0.01). The Western blotting results showed that the expression of SIRT1 protein in the aortic dissection group decreased with age (P<0.01). The MCP-1 protein expression of younger and middle age patients in the aortic dissection group was increased compared with that in the control group (the younger group: 0.65±0.27 vs. 0.38±0.22; the middle age group: 1.08±0.30 vs. 0.46±0.36, P<0.001). MCP-1 expression increased with age (P<0.01). The result of immunohistochemical staining for SIRT1 protein was similar to that of Western blotting.ConclusionThe expression of SIRT1 decreases in patients with aortic dissection disease, and declines with age. SIRT1 may play an important role in the treatment and screening of type A aortic dissection.