Abstract:Atherosclerosis (As) is a chronic inflammatory disease in which adaptive immune cells play an important role, including immune cells and cytokines that regulate the balance between pro-inflammatory and anti-inflammatory. Traditional Chinese medicine is widely used in the prevention and treatment of As due to its advantages of multiple pathways and targets. In this paper, the mechanism of synergistic pro-inflammatory and anti-inflammatory effects of different immune cell subsets in As inflammatory response and the influence of traditional Chinese medicine regulating immune balance on As were reviewed.

Abstract:Aim To confirm the role of kinesin superfamily member 16B (KIF16B) in the process of low density lipoprotein cholesterol (LDLC) uptake of hepatocyte which is regulated by the inducible degradation of low density lipoprotein receptor (IDOL). Methods The intracellular fluorescence intensity was observed by the inverted fluorescence microscope. The intracellular lipid content was measured by oil red O staining, and the LDLC uptake was detected by DiI-LDL uptake experiment. The low density lipoprotein receptor (LDLR) abundances on the cell surface of hepatocytes were assayed by immune flow cytometry. The protein expression of IDOL, KIF16B and LDLR was detected by Western blot, and the interaction between LDLR and KIF16B protein was carried out by co-immunoprecipitation. Results Compared with white light view, the observed green fluorescence results showed that both HepG2 and LO2 cells were infected by the RNA-interference or overexpression IDOL(RNAi/OE-IDOL) lentivirus. Compared with the non-lentivirus infected control group, both the intracellular lipid and the ability of the LDLC uptake were significantly decreased in the OE-IDOL group(P＜0.05), and also decreased in the abundances of LDLR on the surface of hepatocytes (P＜0.01); and vice versa, the contrary results of these three experiments were observed in the RNAi-IDOL group (P＜0.01), which indicated that overexpression IDOL would reduce the LDLC uptake of hepatocytes. Compared with the RNAi/OE-IDOL control group, the expression of LDLR and KIF16B protein was increased in the RNAi-IDOL group (P＜0.01), and the interaction between KIF16B and LDLR was enhanced (P＜0.01). While in the overexpression IDOL of HepG2 and LO2 cells, the expression of LDLR and KIF16B protein was decreased (P＜0.05), meanwhile the interaction between LDLR and KIF16B was correspondingly weakened. Conclusion The interaction between KIF16B and LDLR possibly affects the process of that IDOL regulates LDLC uptake of hepatocytes.

Abstract:Aim To explore the effect of Curcumin on that inducible degrader of the low density lipoprotein receptor (IDOL) regulating the uptake of low density lipoprotein cholesterol (LDLC) of hepatocytes. Methods HepG2 and LO2 cells (two kinds of hepatocytes) were infected with the constructed overexpression or RNA-interference IDOL (OE/RNAi-IDOL) lentivirus. The efficiency of the lentiviral infection experiment was evaluated by fluorescence microscopy. The expression of IDOL and low density lipoprotein receptor (LDLR) proteins was detected by Western blot. After HepG2 and LO2 cells were treated with Curcumin for 24 hours, intracellular lipid droplets were determined by red oil O staining; cholesterol content was detected by using cholesterol testing kits; the uptake of LDLC by hepatocytes was detected by DiI-LDL uptake experiment; LDLR abundances of hepatocytes surfaces were determined by immune flow cytometry. Results Compared with white light view, the phenomenon of the green fluorescence was observed both in HepG2 and LO2 cells infected by OE-IDOL and RNAi-IDOL lentivirus; Western blot results showed that both in HepG2 and LO2 cells infected by RNAi-IDOL-2 lentivirus, IDOL protein expression were decreased, while LDLR expression was increased (P＜0.01); on the contrary, in HepG2 and LO2 cells infected by OE-IDOL lentivirus, IDOL protein expression was increased, while LDLR expression was decreased, the above results indicated that both HepG2 and LO2 cells infected by OE/RNAi-IDOL lentivirus had been acquired. Compared with the control group of HepG2 and LO2 cells without any treatment, after 25 μmol/L Curcumin treatment for 24 hours in the OE/RNAi-IDOL lentivirus infected cells, both the intracellular lipid droplet content and relative cholesterol content were increased in the treatment group (P＜0.01), meanwhile the uptake LDLC ability and cell surface LDLR abundances of hepatocytes were also enhanced (P＜0.01), the same trend was also observed in the results of Rosuvastatin treatment group. Conclusion The levels of IDOL protein in liver cells were down-regulated by Curcumin, which further promotes the uptake of LDLC of liver cells.

Abstract:Aim To investigate the mechanism of Chuanxiong in the treatment of atherosclerosis (As) based on network pharmacology and molecular docking. Methods TCMSP database was used to screen the active components of Chuanxiong, and Swiss target prediction was used to predict the drug targets. The relevant targets of As were screened in the databases of DrugBank and DisGeNET. The target protein interaction network was constructed by STRING, and the network was drawn by Cytoscape and analyzed by topology. Omicshare was used for GO enrichment analysis and KEGG enrichment analysis. DockThor was used for molecular docking. Results 167 related therapeutic targets were obtained. 46 targets, including CASR and MAPK3 etc. were found to be the core targets by network topology analysis. GO enrichment analysis showed that Chuanxiong could affect the occurrence and development of As in biological process, molecular function and cell composition. KEGG pathway enrichment analysis showed that Chuanxiong might play a role in the treatment of As by regulating multiple metabolic pathways such as neuroactive ligand receptor interaction and calcium signaling pathway etc. Conclusions By using network pharmacology method, it was confirmed that Chuanxiong had the characteristics of multi-channel and multi-target action in the treatment of As. The possible mechanism of Chuanxiong in the treatment of As was predicted, which provided a reference and theoretical basis for its subsequent basic research.

Abstract:Aim To explore the effect of TanshinoneⅡA(TanⅡA) on macrophage polarization by inhibiting histone deacetylase 3(HDAC3). Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was applied to screen drug targets of TanⅡA and therapeutic targets of atherosclerosis(As). The intersection genes were enriched and visualized by KEGG pathway analysis and Cytoscape 3.7.1 software, respectively. THP-1 monocytes were induced as adherent macrophages by phorbol 12-myristate- 13-acetate(PMA), and divided into four groups:M0 group, oxidized low density lipoprotein(ox-LDL) group, TanⅡA＋ox-LDL group and ox-LDL＋HDAC3 siRNA group. Flow cytometry, immunofluorescence and qRT-PCR were used to detect the change of polarization and expression of HDAC3 mRNA in macrophage. Results Twenty-three intersection genes were obtained of TanⅡA drug targets and As therapeutic targets by Bioinformatics analysis. The top twenty signal pathways were selected for visual analysis and displayed that these genes concentrated in signaling pathways such as atherosclerosis, fluid shear force and TNF signaling pathway, among which JUN, FOS, RELA and NFKBIA, were involved in the regulation of macrophage polarization. Results of Flow cytometry, immuno fluorescence and qRT-PCR showed that ox-LDL could significantly increased the expression of CCR7 and CCL2 in M0 macrophages. Compared with ox-LDL group, HDAC3, CCR7 and CCL2 expression decreased in TanⅡA＋ox-LDL group, consistent with ox-LDL＋HDAC3 siRNA group. Conclusion TanⅡA could effectively prevent ox-LDL-induced macrophage polarization toward M1 direction, the mechanism may be mediated by regulating HDAC3 expression.

Abstract:The endoplasmic reticulum-mitochondrial structure coupling mitochondrial associated endoplasmic reticulum membranes (MAM) is a dynamic membrane area formed by the coupling of mitochondria and the endoplasmic reticulum, and MAM can participate in the information exchange between these two organelles. MAM has been confirmed to be involved in calcium signaling, lipid balance, mitochondrial dynamic changes, mitochondrial autophagy and endoplasmic reticulum stress response. MAM is closely related to cardiovascular diseases, Alzheimer disease and metabolic diseases.This paper describes the protein composition and function of MAM and its relationship with diseases.

Abstract:Aim To investigate the longitudinal association between handgrip strength and risk of hypertension in the middle-aged and elderly population in China. Methods The participants aged 45 years and older were selected from the China health and retirement longitudinal study(CHARLS). Multivariate Logistic regression models or linear regression models were used to analyze the associations of handgrip strength with hypertension and blood pressure. In the primary analysis, the relative maximum handgrip strength (maximum handgrip strength/body mass index) was divided into three groups according to the tertiles. Results A total of 5 876 subjects were included in this study. After an average follow-up of 3.85 years, the incidence of hypertension was 19.11%. The incidence of hypertension was increased with the decreasing of handgrip strength (P_trend＜0.05). The multivariate Logistic regression model showed that relative handgrip strength was negatively associated with the risk of hypertension after adjusting for general demographic, lifestyle, health status and other factors. The risk of hypertension in the high relative handgrip strength group was 46% (RR:0.4,5%CI:0.34～0.84, P＜0.01) and 59% (RR:0.1,5%CI:0.26～0.67, P＜0.01) lower than that in the low relative grip strength group for men and women, respectively. The systolic and diastolic blood pressure levels in high relative handgrip strength group were 3.03 mmHg and 1.33 mmHg (P＜0.05) lower than those in the low relative handgrip strength group for men, and were 4.48 mmHg and 1.92 mmHg (P＜0.05) lower than those in the low relative handgrip strength group for women. Conclusions The handgrip strength was longitudinally associated with the high risk of hypertension in middle-aged and elderly population. It suggested that handgrip strength may be a predictor of hypertension.

Abstract:Aim To compare the clinical efficacy of dabigatran and warfarin in acute myocardial infarction with left ventricular thrombosis (LVT). Methods A total of 116 patients diagnosed with acute myocardial infarction and LVT who were hospitalized in Liaoning Provincial People's Hospital from september 2015 to march 2020 were collected and randomly divided into warfarin group and dabigatran group. Stroke rate, bleeding event rate, coagulation function indexes before and after 3 months of treatment, liver function indexes before and 1 month and 3 months after treatment were observed, and the disappearance time of thrombosis, new thromboembolic events and bleeding events during treatment were compared between the two groups. Results During the treatment, the dabigatran group had fewer total embolization events than the warfarin group (3.4% vs 24.1%, P＝0.002), of which cerebral embolism (1.7% vs 15.5%, P＝0.016) was statistically significant (P＜0.05); There was no statistically significant difference in prothrombin time(PT), thrombin time(TT) and fibrinogen(FIB) between the two groups (P＞0.05), activated partial thromboplastin time(APTT) was higher in the dabigatran group than that in warfarin group (P＜0.05). There was no statistically significant difference in liver function indexes of patients 1 month and 3 months after treatment between the two groups (P＞0.05). Compared with the warfarin group, the patients in the dabigatran group had a shorter thrombus disappearance time ((47.00±5.30) days vs (69.10±7.90) days, P＜0.01). The number of cases of left ventricular thrombus disappearance in dabigata group was significantly more than that in warfarin group(77.6% vs 39.7%, P=0.032). The incidence of bleeding in dabigatran group was lower than that of warfarin group (3.4% vs 17.2%, P＜0.05). Conclusion Dabigatran is safer and more effective than warfarin in the treatment of patients with acute myocardial infarction and left ventricular thrombosis.

Abstract:Aim To investigate the changes of serum miR-1, miR-133a and miR-208a levels in patients undergoing on-pump coronary artery bypass surgery (ONCABG) and off-pump coronary artery bypass grafting (OPCABG). Methods From February 2016 to February 9,4 patients with multiple coronary artery disease requiring CABG in our hospital were selected. According to the operation method, 94 patients were divided into ONCABG group (n＝47) and OPCABG group (n＝47). The serum miR-1, miR-133a and miR-208a levels were detected by quantitative real-time PCR in all patients before operation and at different time after operation. The levels of serum cardiac troponin I (cTnI) and creatine kinase isoenzyme MB (CK-MB) were detected by chemiluminescence immunoassay in all patients before operation and at different time after operation. The correlation between serum miR-1, miR-133a, miR-208a levels and cTnI, CK-MB levels was analyzed. Results Compared with preoperative, the serum levels of miR-1, miR-133a, miR-208a, cTnI and CK-MB were increased in both groups at 4 h and 24 h after operation (P＜0.05). Compared with 4 h after operation, the serum levels of miR-1, miR-133a, miR-208a, cTnI, and CK-MB were decreased in the two groups at 24 h after operation (P＜0.05). Compared with ONCABG group, the serum levels of miR-1, miR-133a, miR-208a, cTnI and CK-MB were lower in OPCABG group at 4 h and 24 h after operation (P＜0.05). Pearson analysis showed that the serum miR-1, miR-133a and miR-208a levels were positively correlated with cTnI and CK-MB levels at 4 h and 24 h after operation in the two groups (P＜0.05). Conclusion miR-1, miR-133a, and miR-208a are expected to be important biomarkers for judging myocardial injury after ONCABG and OPCABG. This study provides a certain reference for the clinical selection of ONCABG and OPCABG.

Abstract:Aim To compare the efficacy and safety of bare metal stent (BMS), drug-coated balloon (DCB) and drug-eluting stent (DES) in coronary heart disease patients with high bleeding risk (HBR). Methods Domestic and international electronic databases were searched to collect randomized controlled clinical trials of DCB or DES vs. BMS in coronary heart disease patients with HBR, Meta-analysis was performed using Revman 5.3 software. The primary endpoints of this study were to compare the target lesion revascularization (TLR) rate, recurrent myocardial infarction rate, cardiogenic mortality rate and bleeding rate of DCB and DES vs. BMS in coronary heart disease patients with HBR. The secondary endpoints were to indirectly compare the TLR rate, recurrent myocardial infarction rate, cardiogenic mortality rate and bleeding rate of DCB and DES, so as to compare the clinical effect of the three. Results In coronary heart disease patients with HBR, compared with BMS group, DCB group and DES group had lower TLR rate (RD＝－0.4,5%CI:－ 0.05～0.03, P＜0.05), lower cardiogenic mortality rate (RD＝－0.2,5%CI:－0.04～－0.01, P＜0.05), and lower recurrent myocardial infarction rate (RD＝－0.3,5%CI:－0.05～0.01, P＜0.01). Compared with DES group, DCB group had lower TLR rate (0% vs. 5.5%, RR＝0.6,5%CI:0.00～0.98, P＝0.05) and recurrent myocardial infarction rate (0% vs. 5.8%, RR＝0.6,5%CI:0.00～0.93, P＜0.05). Patients in the three groups were treated with very short dual antiplatelet therapy (DAPT) program, and there was no significant difference in bleeding rate among the three groups. Conclusion In coronary heart disease patients with HBR, DCB and new generation DES combined with short-term DAPT have higher efficacy and safety than BMS.

Abstract:Cardiovascular disease (CVD) has become one of the leading causes of death worldwide. Although the research on CVD has made some progress, there are still many problems to be further studied. In recent years, the newly discovered pyroptosis is a kind of programmed cell death accompanied by inflammatory reaction. Studies have shown that pyroptosis plays an important role in the occurrence and development of CVD. This article reviews the role and mechanism of pyroptosis in atherosclerosis, myocardial infarction, diabetic cardiomyopathy, myocarditis and other CVD.

Abstract:Almost all life on earth has an internal mechanism-circadian rhythm, and the circadian clock that controls the circadian rhythm has been revealed as an important regulator of physiology and disease. Circadian rhythm is closely related to atherosclerosis(As). Various studies have shown that impaired circadian clocks and disturbed sleep can affect hematopoiesis process and glucose and lipid metabolism of As,and change the cellular behavior in local plaque lesions. At the molecular level, circadian rhythm can regulate atherosclerotic inflammation and vascular remodeling through the Toll like receptor (TLR) pathway, improve endothelial function and insulin signaling through the protein kinase B (Akt) pathway, and affect the recruitment of monocytes and activation of lymphocytes through the CCL2-CCR2 signal axis.This review discussed the role and molecular mechanisms of circadian rhythm in As, in order to better understand the connection between As and the circadian clock system.

Abstract:Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries, which can lead to ischemic heart disease, stroke, peripheral vascular disease and other cardiovascular and cerebrovascular diseases, seriously endangering human health. Intraplaque hemorrhage is an important feature of advanced plaque, and it has been proved that it can accelerate the progression of plaque in a short time, which is mainly related to the influence of blood cells into the plaque on the level of inflammation in the plaque. The purpose of this paper is to review the role of blood cell components in the regulation and outcome of inflammation in hemorrhagic plaque.

Abstract:Since the discovery of pneumonia infected by the new coronavirus (SARS-CoV-2), it has brought great pressure to China's public health cause. With the in-depth study of the new coronavirus, it was found that SARS-CoV-2 infection is closely related to myocardial injury in patients. More and more attention has been paid to the myocardial damage caused by the new coronavirus in clinic. This article reviews the possible pathogenesis, diagnosis, and treatment of myocardial injury associated with novel coronavirus infection, with a view to providing assistance to the treatment of SARS-CoV-2 infection in patients with cardiovascular disease.