Abstract:Atherosclerosis is a complex, chronic disease caused by multiple factors, which is characterized by lipid accumulation, smooth muscle cell migration into the intima and proliferation, inflammatory cell infiltration, collagen deposition and plaque formation in the vessel wall of large- and medium-sized arteries. A growing body of evidence suggests that NLRP3 inflammasome, pyroptosis, exosomes, gut microbiota, peripheral vascular adipose tissue(PVAT), non-coding RNA and so forth are closely associated with the occurrence and development of atherosclerosis. Studying the role of NLRP3 inflammasome, pyroptosis and other factors in the development of atherosclerosis will help to further understand the pathogenesis of atherosclerosis and find new more effective therapeutic pathways and biomarkers. This review will summarize and discuss the current knowledge on the role of NLRP3 inflammasome, pyroptosis, exosomes, gut microbiota, PVAT, non-coding RNA in atherosclerosis development, specifically concentrating on the latest research progresses of Chinese scholars in the past two years.

Abstract:Aim To observe the effects of components of Xiongshao capsule on cholesterol and inflammatory factors on foam cells in vitro. Methods Oxidized low-density lipoprotein (ox-LDL) was used to induce the foaming of RAW264.7 cells. The proliferation activity of foam cells was detected by CCK-8 reagent. The total cholesterol (TC) and free cholesterol (FC) in foam cells were detected by cholesterol test kit, and the lipid distribution in cells was observed by oil red staining. The concentration of inflammatory factors, tumor necrosis factor alpha (TNF-α) and interleukin 1beta (IL-1β) was detected by ELISA kit. Results The results of CCK-8 showed that ligustrazine and paeoniflorin had no obvious effect on the proliferation of foam cells under 80 mg/L concentration. 40 mg/L ligustrazine plus 80 mg/L paeoniflorin could significantly reduce TC and FC contents in foam cells, reduce lipid deposition in foam cells, and inhibit the secretion of TNF-α and IL-1β by foam cells. Conclusion It is proved that the effective components of Xiongshao capsule, ligustrazine and paeoniflorin, can reduce the cholesterol content in foam cells derived from RAW264.7 cells and reduce the inflammatory factors, TNF-α and IL-1β produced by foam cells which have an potential ability to inhibit inflammatory reaction.

Abstract:Aim The differential gene expression, signaling pathways and protein network were analyzed from the gene chip data for carotid atherosclerotic plaques. Methods GSE43292 was downloaded from the gene expression omnibus (GEO) database and the data was adjusted. The significant differential genes were analyzed by R software in GSE43292. The geneontolgy (GO) analysis and pathway analysis were performed by bioinformatics GSEA, and the significant differential gene was analyzed by Cytoscape. Results After GSE42392 was analyzed, the 87 up-regulated genes and the 60 down-regulated genes were found as the significant different expression gene (P<0.01) between the atherosclerotic plaques and the distant tissues in carotid artery. The heatmap showed the different expression genes. The enriched GO analysis of GSEA revealed that the main differential expressions were associated with the antigen binding, the serine hydrolase activity and the chemokine receptor binding. The pathway analysis of GSEA revealed that the main differential expression were associated with hematopoietic stem cells, lysosomal and cytokine receptor interactions. Cytoscape analysis performed the five core genes, including IL-8, CXCL-10, SELE, MMP-9 and IL-18. Conclusions The bioinformatics analysis of GSE42392 data revealed that the differential genes enriched the related signaling pathways and the core genes were found between the atherosclerotic plaque and the distant tissue in carotid atherosclerotic plaques. These research provided the basic data for atherosclerosis research and treatment.

Abstract:Aim To explore the mechanism of ginsenoside Rb1 inhibiting arsenic sulfide-induced toxicity of neurocyte pheochromocytoma cells (PC12). Methods PC12 cells were treated with 0,2.5,5, 0,5, 0,0 μmol/L arsenic sulfide. Cell damage was observed, and cell viability was measured by thiazole blue method. 5,0, 20 μmol/L ginsenoside Rb1 was added into PC12 cell culture medium damaged by arsenic sulfide, and its effect on cell proliferation was detected by sulforhodamine B assay, cell apoptosis was detected by flow cytometry, ATP content in cells was detected by ATP kit luciferase assay, and intracellular reactive oxygen species (ROS) content was detected by 2′,7′-dichlorotetrafluoroethane diacetate probe dyeing. Western blot was used to detect the protein expressions of protein kinase B (AKT), glycogen synthase kinase 3β (GSK-3β), nuclear factor of activated T cell (NFAT), cytochrome C (Cyt C), cysteine protease 3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) in PC12 cells. Results The PC12 cells were damaged by different concentrations of arsenic sulfide, with the increase of the concentration and the prolongation of the action time, the cell damage became more serious; Arsenic sulfide could inhibit the proliferation of PC12 cells. Ginsenoside Rb1 had protective effect on PC12 cells damaged by arsenic sulfide and could effectively inhibit apoptosis of PC12 cells induced by arsenic sulfide. Arsenic sulfide could decrease ATP content and increase ROS content in PC12 cells, and ginsenoside Rb1 could increase ATP content, reduce ROS content and enhance cell metabolism. After arsenic sulfide stimulation, the protein expressions of p-AKT, p-GSK-3β, NFAT-c3, Bcl-2 and Cleaved Caspase-3 in PC12 cells was significantly decreased, the protein expressions of Caspase-3 and Bax was significantly increased, and the expression of Cyt C in mitochondria was significantly increased (P＜0.01). After ginsenoside Rb1 intervention, the protein expressions of p-AKT, p-GSK-3β, NFAT-c3, Bcl-2 and Cleaved Caspase-3 increased significantly, the protein expressions of Caspase-3 and Bax decreased significantly, and the expression of Cyt C in mitochondria decreased significantly (P＜0.01). Conclusion Ginsenoside Rb1 can inhibit arsenic sulfide-induced apoptosis of PC12 cells and protect neurons, which may be achieved by regulating AKT/GSK-3β/NFAT signaling pathway.

Abstract:Aim To investigate the mechanism of cerebral infarction on regulating microglias M1/M2 phenotypic transformation by retinoid acid receptorrelated orphan receptor α(RORα). Methods (1) Directionally transform microglias into the M1 state and the M2 state, the expression of RORα, M1 marker inducible nitric oxide synthase (iNOS) and M2 marker arginase-1 (Arg-1) were deteced by Western blot. (2) Middle cerebral artery embolism (MCAO) model were established, the protein expression of RORα, iNOS, Arg-1 in brain tissues were detected by Western blot after ischemic brain injury at different time points (6 h, 24 h, 3 d and 7 d). (3) RORα-siRNA was injected intracerebroventricularly of mice and MCAO model were established 72 h later, brain function was evaluated by neurobehavioral score (Longa score), the protein expressions of iNOS, Arg-1 and RORα in brain tissues were detected by Western blot. (4) RORα-overexpressed lentivirus was injected intracerebroventricularly of mice, MCAO model were established 7 d later, brain function was evaluated by neurobehavioral score (Longa score), the protein expressions of iNOS, Arg-1 in brain tissues were detected by Western blot. Results Microglias can transform to M1 state induced by LPS/IFN-γ and transform to M2 state induced by IL-4/IL-13. Compared with the control group, RORα expression was significantly increased in M2 state microglias and significantly decreased in M1 state microglias (P<0.01). After cerebral ischemia reperfusion, compared with the Sham group, protein expression of iNOS were significantly increased and peaked in 6 h, then gradually decreased, protein expression of Arg-1 gradually increased in 3 d and 7 d, protein expression of RORα were increased and peaked in 3 d, then significantly decreased in 7 d, the results suggested that M1 state microglias were dominant in cerebral ischemia injury early stage, and M2 state microglias were dominant in cerebral ischemia injury late stage, RORα was highly expressed in the medium stage of cerebral ischemia reperfusion. After down-regulation of RORα expression, the neurobehavioral score was significantly increased, brain function were injured seriously, the protein expression of Arg-1, RORα were significantly decreased and the protein expression of iNOS were significantly increased in MCAO group. After up-regulation of RORα expression, the neurobehavioral score of MCAO group were decreased significantly, the brain function injury was improved. The protein expression of Arg-1 were significantly increased and the protein expression of iNOS were significantly decreased in MCAO group. Conclusion RORα was involved in brain injury after cerebral infarction by regulating the transformation of microglias from M2 state to M1 state.

Abstract:Aim To investigate the application value of monocyte (MONO) to high density lipoprotein (HDL) ratio (MHR) in the early screening of peripheral arterial disease (PAD). Methods 131 patients hospitalized in our hospital from January 1,7 to December 1,7 were retrospectively analyzed. According to the results of color Doppler ultrasonography of lower extremity arteries, the patients were divided into two groups:(1)80 patients in the disease group had obvious stenosis (＞50%) and/or occlusion of lower extremity arteries; (2)51 patients in the control group had normal lower extremity arteries. General information and laboratory findings of patients were collected. The difference of MHR was compared between two groups. The predictive values of MONO, HDL and MR for PAD were assessed.Results There were no significant differences in general condition, blood routine and biochemical indexes between the two groups (P＞0.05). MONO and MHR in the disease group were significantly higher than those in the control group, and HDL was significantly lower than that in the control group (P＜0.001). ROC curve analysis showed that the areas under the curve of MONO, HDL and MR predicting PAD were 0.1,0.657 and 0.820, respectively. The sensitivity of MHR was the highest (88.2%). Compared MHR with MONO (Z＝1.978, P＝0.048), MHR with HDL (Z＝2.963, P＝0.002), the differences were statistically significant. Conclusion MONO, HDL and MHR are correlated with PAD, while MHR is more sensitive and valuable for early prediction of PAD.

Abstract:Aim To investigate the effect of continuous intravenous injection of nicorandil on the incidence of contrast-induced acute kidney injury (CI-AKI) in patients with acute ST-segment elevation myocardial infarction(STEMI) undergoing primary percutaneous coronary intervention(PPCI). Methods A total of 397 patients with STEMI undergoing PPCI were enrolled in this prospective randomized controlled trial. Patients were randomly assigned into two groups:the nicorandil group(n=199)and the control group(n=198). The primary outcome was the incidence of CI-AKI, the secondary outcomes included the major adverse cardiovascular events (MACE) during hospitalization and the need of renal replacement therapy. Results The average of myocardial ischemia was (6.1±2.1) hours. No significant difference was observed in Mehran score and other baseline characteristics between groups (P>0.05). The median duration of blood sampling time after operation was 28.5(25.3,9.6)hours. As a result, there were 53(13.4%) out of 397 patients suffered from CI-AKI, 17(8.5%) in the nicorandil group and 36(18.2%) in the control group, respectively (P<0.05). In the multivariate Logistic regression model, nicorandil acted as an independent protective factor of CI-AKI(OR=0.38, 95% CI 0.20～0.72, P=0.003). Whereas, the volume of CM(OR=1.03, 95% CI 1.01～1.04, P<0.001)was an independent risk factor for CI-AKI. The incidence of angina within 24 hours post PPCIin control group was higher than that in nicorandil group (P<0.05). There was no significant difference in MACE, and renal replacement therapy between the two groups (P>0.05). Conclusion Intravenous injection of nicorandil perioperatively can reduce the incidence of CI-AKI in STEMI patients undergoing PPCI, but does not improve the short-term prognosis.

Abstract:Aim To study the dynamics of homocysteine (Hcy) and carotid atherosclerosis in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and the high risk of stroke, and to investigate the clinic application of the combination of Hcy and carotid ultrasound in screening OSAHS in population with the high risk of stroke. MethodsSelect a total of 200 patients who were found to be snoring during night sleep with the screening of stroke. Analyze the diagnostic value of the combination of plasma Hcy and carotid artery ultrasound for OSAHS in patients with high risk of stroke. Results The incidence of OSAHS in this study was 46.50%. There was no significant difference in clinic characteristics between two groups (P>0.05). Plasma Hcy level in OSAHS group was significantly higher than the control groups (P<0.05). According to carotid ultrasound, intima-media thickness (IMT) in OSAHS group was much thicker than the control group (P<0.05). The positive correlation between plasma Hcy and IMT was observed in OSAHS group (r=0.65, P<0.05). The cut-off value of plasma Hcy in OSAHS diagnosis was 24.045 μmol/L, and its area under curve (AUC) was 0.730. The specificity and sensitivity were 68.2% and 66.7%, respectively. 0.824 mm of IMT under carotid ultrasound was the best in OSAHS diagnosis, with AUC of 0.970, the specificity of 90.3% and the sensitivity of 91.6%. The sensitivity of the combination of plasma Hcy and IMT in OSAHS diagnosis was 60.21% and the specificity and false positive rate were 97.20% and 2.89%. Conclusion Plasma Hcy combined with carotid ultrasound could be applied as a screening method of OSAHS in population with high risk of stroke, which has high specificity.

Abstract:Aim To investigate the changes of peripheral circulating endothelial progenitor cells (EPCs) and fibrinolysis, adhesion and inflammatory factors expressions of EPCs in patients with coronary heart disease (CHD). Methods 57 patients with CHD (CHD group) and 30 cases with control (control group) were selected, and EPCs were extracted and compared in number and cell colony. Concentrations and activities of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI) secreted by EPCs were detected by enzyme-linked immunosorbent assay and substrate chemiluminescence methods. The mRNA expressions of tPA, PAI, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and peroxisome proliferator activated receptor γ (PPARγ) in EPCs were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results The number of EPCs in CHD group was significantly lower than that in control group (P＜0.05), the number of forming cell colony and the ability of cell proliferation were also significantly lower (P＜0.05). Compared with the control group, the content and activity of tPA secreted by EPCs in CHD group decreased significantly (P＜0.05), and the content and activity of PAI increased significantly (P＜0.01). RT-PCR results showed that compared with the control group, the mRNA expressions of tPA and PPARγ in EPCs of CHD group decreased, while the mRNA expressions of PAI, VCAM-1 and ICAM-1 increased (P＜0.05). Conclusion The decrease of EPCs in peripheral blood circulation, the reduction of fibrinolytic function and the increase of adhesion and inflammatory factor expression in patients with CHD play an important role in the occurrence and development of CHD.

Abstract:Aim To evaluate the correlation of platelet/lymphocyte ratio (PLR) and risk stratification and in-hospital prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), and to examine whether PLR combined with Grace risk score can improve the predictive value of Grace risk score for in-hospital major adverse cardiovascular events (MACE). Methods 372 patients diagnosed as NSTE-ACS in the Department of Cardiology, Affiliated Hospital of Qingdao University were selected. According to the PLR level at admission, the patients were divided into low PLR group (PLR<97.56), medium PLR group (97.56≤PLR≤133.32), high PLR group (PLR>133.32), 124 cases in each group. Baseline clinical data, Grace score, and MACE between the three groups were compared. According to the presence or absence of MACE, there were 36 patients with MACE and 336 patients without MACE. The differences in baseline clinical data, PLR and Grace score between the two groups were compared. The correlation between PLR, Grace score and in-hospital MACE was evaluated. ROC curve and DELONG method were used to evaluate the predictive value of PLR combined with Grace score and Grace score alone for in-hospital MACE. Results (1) Grace score, the occurrence of in-hospital MACE and acute heart failure were significantly higher in the high PLR group than the low PLR and middle PLR groups, and the differences were statistically significant(P＜0.001). (2) The age, uric acid, platelet count, PLR, Gensini score, and Grace score were significantly higher in the MACE group than those in the no-MACE group, and the diastolic blood pressure, creatinine clearance rate and left ventricle ejection fraction were significantly lower (P＜0.01). (3) PLR was an independent predictor of in-hospital MACE in patients with NSTE-ACS by multivariate logistic regression analysis. (4) The area under the curve of PLR combined with Grace score to predict the incidence of in-hospital MACE was 0.828, and the area was estimated to be 0.793 by using Grace score alone. The difference between the two areas was statistically significant using the ELONG method of MEDCALC(P＜0.05). Conclusions In NSTE-ACS patients, PLR is an independent predictor of in-hospital MACE. PLR combined with Grace score can significantly improve the predictive value of Grace score for in-hospital MACE.

Abstract:Aim To investigate the association of CYP2C19 gene polymorphism with coronary heart disease (CHD) and its types in Shanxi Han population. Methods 693 unrelated Han patients from Shanxi province were randomly collected from January 2017 to June 2018. According to the results of coronary angiography, clinical manifestations, electrocardiogram and myocardial injury markers, 478 cases were classified as CHD group (including 50 cases of stable angina pectoris, 157 cases of unstable angina pectoris, 271 cases of acute myocardial infarction), and 215 cases without coronary artery disease were classified as control group. Then, CYP2C19 genotypes were detected and the difference of genotype and allele distribution were observed and compared between the two groups. Results The frequency of CYP2C19*1/*2 genotype distribution in CHD group was higher than that in control group (P=0.002). The frequency of CYP2C19*2 allele distribution was higher in CHD group than that in control group (P=0.011). There was no significant difference in the frequency of genotype and allele distribution between the control group and three different types of CHD (P>0.05). Moreover, the Logistic regression analysis showed that the CYP2C19*1/*2 genotype was associated with the increased risk of CHD (OR=1.8,5%CI 1.252～2.698), when factors such as sex, age, diabetes, smoking history, hypertension were excluded. Conclusion CYP2C19 gene polymorphism is a risk factor for CHD in Shanxi Han population, but it is not associated with different types of CHD.

Abstract:Aim To investigate the relationship between Helicobacter pylori (Hp) infection and plaque characteristics, lipid metabolism and inflammatory response in patients with coronary heart disease. Methods 178 patients with coronary heart disease who were first diagnosed in our hospital from August 2017 to March 2019 were selected as the subjects of study. According to the results of detection of Hp infection, the patients were further divided into 65 cases of Hp positive group and 113 cases of Hp negative group. The differences of coronary angiographic results, carotid ultrasound plaque characteristics, peripheral blood lipid metabolism and serum inflammatory mediators levels were compared between the two groups. Results The results of coronary angiography showed that there were significant differences in the number of coronary artery lesions and the nature of coronary plaque between the two groups (P＜0.05). Gensini score of Hp positive group was higher than that of Hp negative group (P＜0.01). Plaque area of carotid ultrasound, intima-media thickness in Hp positive group were larger than those in Hp negative group (P＜0.01); There was significant difference in plaque nature between the two groups (P＜0.05). The levels of serum total cholesterol and low density lipoprotein cholesterol in Hp positive group were higher than those in Hp negative group, and the level of high density lipoprotein cholesterol was lower than that in Hp negative group (P＜0.01). The serum levels of interleukin-6, interleukin-18, tumor necrosis factor α and high-sensitivity C-reactive protein in Hp positive group were higher than those in Hp negative group (P＜0.05). Conclusion The combination of Hp infection may be one of the important factors leading to the decrease of plaque stability, the increase of lipid metabolism disorder and the aggravation of inflammatory reaction in patients with coronary heart disease.

Abstract:Cardiovascular disease (CVD) is a kind of disease that poses a great threat to human health. Its occurrence and development are often influenced by many factors of heredity and environment. The gut bacteria are the largest population of bacteria in the human body, affecting the physiological metabolism of the host. In recent years, the interaction between intestinal flora and host has been paid more and more attention. Intestinal microflora plays an important role in human health and disease. Many studies have confirmed that intestinal flora and its metabolites can affect CVD from dyslipidemia, type 2 diabetes mellitus, hypertension, atherosclerosis, heart failure and other aspects. Therefore, it is worth exploring the scheme of using intestinal flora as the target of CVD treatment. This article will systematically review the role of gut bacteria in the pathogenesis of CVD and the methods of regulating gut bacteria to treat CVD.

Abstract:The incidence of acquired aortic diseases, such as aortic dissection, aortic aneurysm and multiple aortitis, is increasing year by year, with a tendency to become common and frequently occurring diseases. These diseases are often in critical condition, difficult to treat and with high risk of operation. However, the molecular mechanism of their pathological process is still unclear. Circular RNA (circRNA) has the characteristics of stability, tissue/developmental stage specificity, conservativeness and variety richness. CircRNA can bind to miRNA or protein, selectively regulate gene splicing or transcription and protein translation, etc. Many studies have found the presence of specific circRNA in acquired aortic diseases, so it is speculated that circRNA may be a potential biomarker and therapeutic target for acquired aortic diseases. This article will review the origin, biological characteristics, functions of circRNA, and some circRNAs which may be involved in the regulation of the molecular mechanisms of acquired aortic diseases.

Abstract:As a layer of specialized cells in the vascular lumen, vascular endothelial cells (VEC) are the key regulatory interface between blood and tissue, so they have also become potential targets for a variety of vascular injury factors.VEC injury is a common physiological change of many chronic diseases, and it is also the initial pathogenesis of many cardiovascular diseases including atherosclerosis. The specific mechanism remains to be further elucidated. Exploring the general pathological mechanism of VEC injury is helpful to improve the development and prognosis of cardiovascular diseases. The article reviews the general mechanism of VEC injury caused by vasoactive substances, inflammatory response, oxidative stress, coagulation system and other factors.