Abstract:Mitochondrial dysfunction can lead to ATP decrease and reactive oxygen species increase in cells. Therefore, mitochondrial dysfunction is considered to be one of the culprit factors of vascular endothelial cell injury. Many causes are related to mitochondrial dysfunction including mitochondrial DNA mutations, mitochondrial fusion and fission imbalance, and mitophagy dysfunction. This review discussed the regulation mechanisms of mitochondrial quality control and mitochondrial dysfunction in vascular endothelial cell injury, which provide new ideas for the effective prevention and treatment of atherosclerosis.

Abstract:Vascular calcification is a common clinical complication in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. It is a significant risk factor for future cardiovascular events in these patients. There are currently no effective medications to slow or reverse the progression of vascular calcification. It has been previously reported that vascular calcification is an actively cellular-mediated pathological process, which shares many similarities to that of bone formation and bone metabolisms. The osteogenic transition of vascular smooth muscle cells plays an important role in vascular calcification. Recently, epigenetic regulators have emerged as key mediators of vascular calcification. This review summarizes our current understanding of epigenetic regulators such as DNA methylation, histone modification and non-coding RNAs in the pathogenesis of vascular calcification. Targeting epigenetic regulators may represent a novel strategy to treat vascular calcification.

Abstract:Aim To observe the effect of sphingosine 1-phosphate receptor 1(S1PR1) on vascular smooth muscle cell proliferation and migration induced by advanced glycation end products (AGE). Methods Human umbilical artery smooth muscle cells (HUASMC) were cultured, and AGE-BSA was obtained by incubating with glucose and albumin. Cells were divided to control, BSA and AGE-BSA treated group. CCK-8 kit was used to detect the proliferation of smooth muscle cells, cell scratching and Transwell assays were applied to study the migration of smooth muscle cells. S1PR1 antagonist VPC23019 or agonist SEW2871 were used to investigate the role of S1PR1 in the proliferation and migration of human umbilical artery smooth muscle cells with BSA or AGE-BSA treatment. Results Compared with control group, BSA and AGE-BSA induced proliferation and migration of human umbilical artery smooth muscle cells, and the effect of AGE-BSA was more significant than that of BSA (P＜0.05). VPC23019, an antagonist of S1PR1, significantly attenuated the proliferation and migration of human umbilical artery smooth muscle cells induced by BSA and AGE-BSA. The S1PR1 agonist SEW2871 itself promoted the proliferation and migration of human umbilical artery smooth muscle cells, and further enhanced the proliferation and migration of human umbilical artery smooth muscle cells induced by BSA, but had no further promotion effect on the proliferation and migration of human umbilical artery smooth muscle cells induced by AGE-BSA. Conclusions Plasma albumin itself can promote the proliferation and migration of smooth muscle cells, and the effect of glycosylated albumin is more remarkable. The activation of S1PR1 is involved in BSA and AGE-BSA-induced proliferation and migration of human umbilical artery smooth muscle cells, and the activation of S1PR1 by AGE-BSA was more significant.

Abstract:Aim To study the effect of asiaticoside on the inflammatory response in the aneurysm wall of rats with cerebral aneurysm by down-regulating TLR9/MyD88/NF-κB p65. Methods The CA rat model was established, they were randomly divided into model group, asiaticoside (50 mg/kg) group, CpG-ODN (TLR9 activator, 4 mg/kg) group, asiaticoside (50 mg/kg) + CpG-ODN (4 mg/kg) group, with 12 rats in each group, another 12 rats were set as sham operation group. After group treatment, the thickness of the cerebral vessel wall and the volume of the aneurysm in the rats were measured, the morphology of cerebrovascular tissue was detected by HE staining, the levels of IL-1β and TNF-α in rat brain blood vessels and serum were detected by enzyme-linked immunosorbent assay (ELISA), the protein levels of TLR9, MyD88, and nuclear NF-κB p65 in rat brain vascular tissues were detected by Western blot. ResultsCompared with the sham operation group, the vascular wall became thicker, the cerebral arteries bulged and showed tumor-like changes and other CA symptoms, the brain blood vessel wall thickness, aneurysm volume, cerebrovascular tissue and serum IL-1β and TNF-α levels, cerebrovascular tissue TLR9, MyD88 levels and nuclear NF-κB p65 protein level increased significantly in the model group (P＜0.05). Compared with the model group, the symptoms of CA became lighter, the brain blood vessel wall thickness, aneurysm volume, cerebrovascular tissue and serum IL-1β and TNF-α levels, cerebrovascular tissue TLR9, MyD88 levels and nuclear NF-κB p65 protein level decreased significantly in the asiaticoside group (P＜0.05); but the symptoms of CA were aggravated, the brain blood vessel wall thickness, aneurysm volume, cerebrovascular tissue and serum IL-1β and TNF-α levels, cerebrovascular tissue TLR9, MyD88 levels and nuclear NF-κB p65 protein level increased significantly in the CpG-ODN group (P＜0.05). Compared with the asiaticoside group, the symptoms of CA were aggravated, the brain blood vessel wall thickness, aneurysm volume, cerebrovascular tissue and serum IL-1β and TNF-α levels, cerebrovascular tissue TLR9, MyD88 levels and nuclear NF-κB p65 protein level increased significantly in the asiaticoside+CpG-ODN group (P＜0.05). Conclusion Asiaticoside can reduce the inflammation of the cerebral artery tissue of CA rats and reduce the tumor size by down-regulating the expression of TLR9/MyD88/NF-κB p65 pathway protein.

Abstract:Aim To explore the effect of brain-derived neurotrophic factor (BDNF) on Sestrin2 expression and angiogenesis-related mechanisms in endothelial cells. Methods Human umbilical vein endothelial cells (HUVEC) were treated with BDNF (100 μg/L) for 1 h, 2 h, 4 h, 6 h, 8 h, and the protein and mRNA expression of Sestrin2 were detected with immunofluorescent staining, Western blot and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. HUVEC were divided into six groups:control group, BDNF (100 μg/L) group, BDNF+TrkB-Fc (1 mg/L) group, BDNF+KT-5823 (500 nmol/L) group, BDNF+L-NAME(NG-nitro-L-arginine methyl ester) (10－4 mol/L) group, BDNF+DMSO(dimethyl sulfoxide)group; after intervention for 4 h, the expression of Sestrin2 was detected with Western blot. HUVEC were divided into four groups:control group, BDNF (100 μg/L) group, BDNF+Sestrin2 siRNA group, BDNF+control siRNA group; after intervention for 6 h, the capacities of cell migration and tube formation were analysed.Results Sestrin2 mRNA increased in 2 h, 4 h, 6 h group compared with that of the 0 h, 1 h group (P＜0.001), while the protein expression of Sestrin2 increased in 2 h, 4 h, 8 h group compared with that of the 0 h, 1 h group (P＜0.05). BDNF-induced increase in Sestrin2 expression was abolished by L-NAME and PKG inhibitor (P＜0.001). BDNF-induced cell migration and tube formation were completely blocked because of the suppressed expression of Sestrin2 by Sestrin2 siRNA (P＜0.01). Conclusion BDNF confers certain aspects of its proangiogenic capacity through NO/PKG/Sestrin2 pathway.

Abstract:Aim To detect the levels of serum soluble cluster differentiation 163 (sCD163) and heme oxygenase-1 (HO-1) in patients with lower extremity atherosclerotic occlusive disease (LEAOD), and to explore the correlation between the levels of sCD163, HO-1 and restenosis after intervention. Methods From May 2016 to February 8,5 patients with LEAOD who were given interventional therapy in the Vascular Surgery Department of Nanyang Central Hospital were selected as the study object. According to the reexamination results, they were divided into two groups:restenosis group (n=47) and non restenosis group (n=68). Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum sCD163 and HO-1 in each group. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sCD163 and HO-1 levels for restenosis in patients with LEAOD, and Logistic regression was used to analyze the influencing factors of restenosis in patients with LEAOD. Results The levels of serum sCD163 and HO-1 in restenosis group were significantly higher than those in non restenosis group (P＜0.05). The results of ROC showed that the AUC of serum sCD163 and HO-1 in the diagnosis of restenosis after LEAOD was 0.863 and 0.736 respectively, and the cut off value was 660.792 μg/L and 15.067 μg/L respectively, at this time, the corresponding sensitivity was 80.9% and 57.4% respectively, and the specificity was 77.9% and 92.6% respectively. The AUC of serum sCD163 combined with HO-1 in the diagnosis of restenosis after LEAOD was 0.896, and the corresponding sensitivity and specificity were 87.2% and 79.4%, respectively. Logistic analysis showed that the high levels of serum sCD163 and HO-1 were independent risk factors for restenosis after LEAOD intervention. Conclusion The levels of sCD163 and HO-1 in serum of patients with restenosis after LEAOD intervention are significantly increased, and both of them participate in the occurrence and development of restenosis after LEAOD intervention, suggesting that sCD163 and HO-1 may be potential biological indicators for early diagnosis and disease assessment of patients with restenosis after LEAOD intervention.

Abstract:Aim To explore the predictive value of the newly defined C-reactive protein (CRP) to albumin ratio (CAR) in determining the degree of coronary artery stenosis compared with other inflammatory markers, such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR). Methods Patients with acute myocardial infarction (n＝203) and patients with non-AMI coronary heart disease (n＝103) hospitalized in the Department of Cardiology of the People's Hospital of Xinjiang Uygur Autonomous Region from January 1,8 to January 1,0 were included. According to the syntax score, AMI group was divided into two groups:low Syntax score group (Syntax score≤22 points, n＝124) and high Syntax score group (Syntax score≥23, n＝79). CAR, NLR, PLR and MLR were measured, the levels of CAR, NLR, PLR and MLR in each group were compared, and the relationship between the levels of CAR, NLR, PLR and MLR and the degree of coronary artery stenosis was evaluated.. Results The levels of CAR, NLR, PLR and MLR in AMI group were significantly higher than those in non-AMI group (P＜0.001). Correlation analysis showed that CAR was significantly correlated with Syntax score (r＝0.634, P＜0.001), while NLR, PLR and MLR were low correlated with Syntax (r＝0.304, P＜0.001; r＝0.463, P＜0.001; r＝0.344, P＜0.001). Logistic regression analysis showed that CAR level was the only independent risk factor for high Syntax score (OR＝1.8,5%CI:1.004～1.161, P＝0.038). Conclusion The level of inflammatory marker CAR is correlated with the degree of coronary artery stenosis, which can be used as a reliable marker to predict the degree of coronary artery stenosis in AMI patients.

Abstract:Aim To investigate the relationship between serum apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1), creatine kinase isoenzyme (CK-MB) and cardiac troponin I (cTnI) levels and the degree of coronary artery stenosis in patients with coronary heart disease (CHD). Methods 120 patients with CHD were selected as the CHD group, and 40 healthy people who underwent a physical examination during the same period were selected as the normal group. The differences of ApoB/ApoA1, CK-MB and cTnI between normal group and CHD group were compared. In addition, patients in the CHD group were divided into three groups of mild, moderate, and severe coronary artery disease according to the Gensini scores, 25 cases, 52 cases, and 43 cases in each group, respectively. The differences of ApoB/ApoA1, CK-MB and cTnI in CHD patients with different stenosis degrees were compared. In addition, Spearman method was used to analyze the correlation between ApoB/ApoA1, CK-MB and cTnI levels and the degree of coronary artery stenosis. Results The levels of ApoB/ApoA1, CK-MB and cTnI in the CHD group were evidently higher than those in the normal group (P＜0.05). The levels of ApoB/ApoA1, CK-MB and cTnI in the moderate CHD group were evidently higher than those in the mild CHD group (P＜0.05), and the severe CHD group were evidently higher than those in the mild and moderate CHD groups (P＜0.05). ApoB/ApoA1, CK-MB and cTnI levels were positively correlated with the degree of coronary artery stenosis (r＝0.4,0.0,0.930, P＜0.05). Conclusion The levels of serum ApoB/ApoA1, CK-MB and cTnI in patients with CHD are positively correlated with the degree of coronary artery stenosis.

Abstract:Aim To investigate the relationship between serum microRNA-26a-5p (miR-26a-5p) level and heart failure (HF) in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). Methods 223 patients with STEMI in our hospital from February to October 2018 were selected as the study objects. According to whether patients with STEMI complicated with HF after PCI, they were divided into HF group (n＝56) and non-HF group (n＝167). The level of miR-26a-5p in peripheral blood of patients with STEMI was detected by real-time fluorescent quantitative PCR. The clinical data and miR-26a-5p levels were compared between the two groups. The predictive value of miR-26a-5p for HF after PCI in STEMI patients was evaluated by ROC curve. Results The age, diabetes history, acute anterior wall STEMI and the time from onset to treatment in HF group were higher than those in non-HF group (P＜0.05). There were time effect, inter group effect and interaction effect in the comparison of miR-26a-5p levels before PCI, 1 day and 7 days after PCI between the two groups (P＜0.001). The area under ROC curve of miR-26a-5p level 7 days after PCI for evaluating STEMI patients complicated with HF was higher than that before PCI and 1 day after PCI (P＜0.001). Logistic regression analysis showed that age, lesion type, time from onset to treatment, and miR-26a-5p level 7 days after PCI were closely related to STEMI patients with HF (P＜0.05). Conclusions miR-26a-5p is closely related to HF after PCI in STEMI patients. The detection of miR-26a-5p level 7 days after PCI can help to predict the occurrence of HF.

Abstract:Aim To observe the distribution and consistency of estimated pulse wave velocity (ePWV) and brachial-ankle pulse wave velocity (baPWV) in the Kailuan study population. Methods A total of 43 235 employees with complete baseline data participated in the baPWV test. The participants were divided into the risk population and normal population according to the presence or absence of conventional cardiovascular risk factors. Multivariate linear regression was used to establish the regression equations between baPWV and quadratic age and mean arterial pressure in the two populations. The ePWV in the two populations was calculated according to the equations. The distribution of ePWV and baPWV was observed. The relationship between ePWV and baPWV was analyzed by paired sample t-test and linear regression. Results In the normal population, ePWV and baPWV were 11.38±0.70 m/s and 12.90±1.17 m/s, respectively. In the risk population, ePWV and baPWV were 14.29±1.85 m/s and 15.74±1.76 m/s, respectively. In the both of two populations, ePWV and baPWV increased with age, higher in men than those in women. ePWV was slightly lower than baPWV (P＜0.001). The results of linear regression analysis indicated that ePWV and baPWV had a good linear correlation in the total population, normal population and risk population, and the linear R² was 0.8,0.279 and 0.388, respectively. Conclusions ePWV and baPWV had a similar age and sex distribution. The difference was relatively small and a good linear correlation was found between ePWV and baPWV. Therefore, ePWV can be a good substitute for baPWV.

Abstract:Aim To investigate the incidence and predictive factors of unsuccessful operation after successful guide wire and microcatheter routing in reverse interventional therapy for chronic total occlusion (CTO) of coronary artery.Methods 310 patients with coronary CTO treated with reverse interventional therapy were analyzed by retrospective analysis. After the guide wire and microcatheter were successfully traced, according to whether the final operation was successful or not, the patients were divided into two groups:success group (n＝278), failure group (n＝32). The differences of clinical data were analyzed between the two groups. Univariate and multivariate analysis were used to explore the related and predictive factors of surgical failure. Results 10.3% (32/310) of the patients failed in the operation after the success of guide wire and microcatheter routing. The CC0-1 grade of Werner collateral circulation, calcification of lesion vessel, lesion length＞20 mm, operation time, contrast agent dosage and X-ray exposure dose in failure group were significantly higher than those in success group (P＜0.05). Univariate analysis showed that calcification of lesion vessel, lesion length＞20 mm and tortuous collateral vessel were associated with failure of reverse interventional therapy (P＜0.05). Multivariate analysis showed that calcification of lesion vessel was an independent predictive factor of reverse interventional therapy failure (P＜0.05). Conclusions Reverse interventional therapy has a high success rate, and the main predictor of failure is coronary vascular calcification. Improving the treatment strategy and instrument of calcified vessels can increase the success rate of reverse interventional therapy.

Abstract:Coronary atherosclerosis is a chronic inflammatory disease that affects the structure and function of coronary arteries, leading to a series of cardiovascular events. In recent years, the study on the pathogenesis of atherosclerosis in the adventitia of coronary arteries has attracted more and more attention. The adventitia is made up of fibroblasts, progenitor cells, immune cells, microvessels and adrenergic nerves, which surround perivascular adipose tissue. All kinds of tissues and cells of the adventitia have high metabolic activity, which can regulate the structure and function of the whole vascular wall “from the outside to the inside” and participate in the formation of atherosclerosis. This paper reviews the recent advances in the pathogenesis of coronary atherosclerosis in the adventitia of arteries.

Abstract:Secreted frizzled related protein 4 (SFRP4) is an antagonistic inhibitor of Wnt signaling and plays an important role in human development. Abnormal gene expression and protein secretion of SFRP4 result in the pathological changes. This review introduced the structural characteristics, tissue distribution and expression pattern of SFRP4 during embryonic development. As an inhibitor of Wnts signaling, SFRP4 plays a key role in regulating adipogenesis. In clinic, the level of SFRP4 protein in the serum of diabetic patients was abnormally increased, which was negatively correlated with insulin secretion, indicating that SFRP4 plays an important role in the process of glucose metabolism and insulin resistance. In recent years, SFRP4 has attracted extensive attention in the research of obesity and lipid metabolism. Systematic research on SFRP4 can not only provide information related to diseases, but also serve as a novel drug and treatment target.

Abstract:Atherosclerosis, leading to formation of plaque on the artery vessel wall, underpins many cerebral and cardiovascular diseases with high mortality rates globally. Nanoparticles promise to advance strategies to treat atherosclerotic disease. Through the rational design of nanoparticles, nano-based delivery systems enable more efficient delivery of a drug to its therapeutic target or even directly to the diseased site, overcoming biological barriers and enhancing a drug’s therapeutic index. In addition, advances in imaging techniques have led to the development of theranostic nanoparticles that may simultaneously act as carriers of both imaging and therapeutic payloads. The following is a summary of nanoparticle diagnosis for atherosclerosis and an overview of recent major advances in the targeted treatment of atherosclerotic disease.

Abstract:Serum amyloid A has a significant effect on the formation of atherosclerosis as an acute reaction, leading to inflammation by stimulating the release of inflammation factors. It is vital for atherosclerosis that serum amyloid A combined with lipoprotein changes the physiological function of high density lipoprotein. Serum amyloid A can affect the function of vascular endothelium and smooth muscle, and also cause thrombosis,which all promote the development of atherosclerosis.

Abstract:After myocardial infarction, there will be a strong inflammatory reaction in the ischemic area, in which a variety of inflammatory cells play a role. Macrophages, as an important component of innate immune response, are very important in the process of tissue repair after myocardial injury. With the development of myocardial infarction, macrophages can differentiate into various subtypes and play a role in phagocytosis of apoptotic cells, angiogenesis, fibrosis and scar maturation. To study the influence of macrophages on myocardial infarction is helpful to explore the improvement of prognosis and diagnosis and treatment of myocardial infarction. This review will focus on the infiltration,polarization and functional changes of macrophages after myocardial infarction.