Abstract:Exercise training is beneficial to the heart. Exercise training will improve the exercise ability and quality of life of patients with cardiovascular diseases, and reduce their mortality and morbidity. Though exercise training benefits in the heart have been well accepted, the underlying mechanism remains to be explored. This review focuses on the main underlying mechanism of exercise benefits in the heart and the research progress of the protective effects of exercise in myocardial infarction, myocardial ischemic reperfusion injury, pathological cardiac hypertrophy, and cardiac aging. It ctims to provide new ideas and strategies for the prevention and treatment of cardiovascular diseases from the unique perspective of “exercise”.

Abstract:Aim To investigate the effects of long-term ezetimibe on hyperlipidemia and genes involved in lipid metabolism in the liver of the LDLR＋/－ hamster. Methods Male LDLR＋/－ hamsters were randomly divided into two groups:the vehicle group and the ezetimibe group (25 mg/(kg·d)). Animals were free to access water and high-fat diet. After 20-week administration, hamsters were sampled after overnight fasting. The plasma levels of total cholesterol (TC), triglyceride (TG), total bile acid (TBA), non-esterified fatty acid (NEFA) and aspartate aminotransferase (AST) were detected by assay kits. Mixed plasma in each group was further separated via an KTA fast protein liquid chromatography (FPLC) system and the TC and TG levels in each fraction were also detected. The expression of multiple genes in the liver and proteins in the plasma was determined by qRT-PCR and Western blot, respectively. Results Long-term ezetimibe intervention significantly decreased plasma TC, TG, TBA, NEFA and AST levels, and apolipoprotein B protein expression in the LDLR＋/－hamsters, and had no effect on the protein levels of lipoprotein lipase (LPL) and proprotein convertase subtilisin/kexin-type 9 (PCSK9) and the activity of LPL. Further KTA-FPLC analysis demonstrated that ezetimibe reduced the TC and TG levels in all the lipoprotein fractions. In the liver, ezetimibe significantly reduced TC, but not TG concentration. Furthermore, ezetimibe significantly increased the mRNA expression of sterol regulatory element binding protein 2 and PCSK9 and dramatically decreased the expression of liver X receptor α, cholesterol 7α-hydroxylase A1, ATP-binding cassette transporter G5 (ABCG5) and ABCG8 in the liver. Conclusion Long-term ezetimibe intervention reduces hyperlipidemia and displays complex modulatory effects on the genes involved in lipid homeostasis in LDLR＋/－ hamsters.

Abstract:Aim To analyze the differences in clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) critically ill patients with or without vascular calcification. Methods COVID-19 critically ill patients admitted to the intensive care unit of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in February 2020 were analyzed retrospectively. According to the chest CT findings, the patients were divided into vascular calcification group and non-vascular calcification group. The vascular calcification group was further divided into aortic calcification group, coronary calcification group and simultaneous calcification group (both aorta and coronary artery calcification). The clinical characteristics and outcomes of patients were compared in different groups. Results Compared with the non-vascular calcification group, the patients in the vascular calcification group were older and had a higher proportion of hypertension and coronary heart disease, which showed higher levels of leukocyte count, neutrophil count, C-reactive protein, globulin, lactate dehydrogenase, international normalized ratio, D-dimer, creatinine, creatine kinase-MB, high-sensitivity cardiac troponin, myohemoglobin and N-terminal pro-B-type natriuretic peptide, lower levels of lymphocyte count, platelet count, albumin, estimated glomerular filtration rate, and higher risk of death. Compared with aortic calcification group, the outcomes of coronary calcification group and simultaneous calcification group were worse. Conclusion Vascular calcification, especially coronary artery calcification, may be a risk factor for poor prognosis in COVID-19 critically ill patients.

Abstract:With the changes of living standard and lifestyle, metabolic cardiovascular diseases characterized by obesity are increasing by years. The disorder of adipose function and adipocytokines, because of adipose tissue’s pathological expansion induced by obesity, participates in the whole process of the occurrence and development of cardiovascular disease. This article reviews different types of adipose tissue involve in maintenance of cardiovascular homeostasis or regulation of cardiovascular disease by endocrine or paracrine effects under physiological or pathological conditions. Therefore, it provides new ideas and new targets for the precise treatment of obesity-related metabolic cardiovascular diseases.

Abstract:Aim To observe the changes in the expression level of NOD-like receptor pyrin domain containing 3(NLRP3) inflammasomes at different stages of the course of atherosclerosis (As) and the intervention effect of Trichosanthis Fructus-Allii Macrostemonis Bulbus through establishment of the model of atherosclerosis in ApoE－/－ mice. Methods High-fat-fed ApoE－/－mice for 6,0, 34 weeks were randomly divided into model groups (M1, M2, M3) and medication groups (6g/(kg·d))(GX1, GX2, GX3), 10 mice in each group. C57BL/6 mice were set as blank control group(C1, C2, C3). The mice in the blank control group and the model group were given normal saline by gavage, and the mice in the medication group were given the corresponding drugs by gavage daily for 4 weeks. After the experiment, the mice were sacrificed and the aortic plaque area and morphology were evaluated by oil red O staining. HE staining was used to observe the pathomorphological changes of the aorta. Immunohistochemical method was used to detect NLRP3 expression in the aorta. The levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in serum were detected by ELISA. Western blot was used to detect the protein expression of NLRP3, apoptosis-associated speck-like protein containing (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1) in aortic tissue. qRT-PCR was used to detect the mRNA expression of NLRP3, ASC, Caspase-1 in aortic tissue. Results At different stages of the course of As, lipid accumulation and plaque area in aorta of mice were significantly increased in model group, the levels of IL-1β and IL-18 in serum was continuously increased, and the protein and mRNA expressions of NLRP3 and ASC were continuously up-regulated, the protein expression of Caspase-1 also showed an upward trend, but there was no statistical significance between M2 and M3. Compared with the model group, the lipid accumulation and plaque area in aorta of mice at different stages were significantly decreased in medication group, and the levels of IL-1β and IL-18 in serum were decreased; The protein and the mRNA expression of NLRP3, ASC and Caspase-1 in aortic tissues were significantly down-regulated. ConclusionsNLRP3 inflammasome was involved in the pathological process of aorta As. Trichosanthis Fructus-Allii Macrostemonis Bulbus drug parican regulate the expression of NLRP3 inflammasomes at different stages in the aorta of As model mice, and thus play a role in protecting As.

Abstract:Aim Through the exoRBase database to screen the differentially expressed exosomal genes and build the CeRNA network in the peripheral blood of coronary heart disease (CHD), and then explore the key genes and regulatory mechanisms leading to the onset and progression of CHD. Through the key genes of differentially expressed mRNA who were enriched by GO and KEGG analysis, to study the molecular function and biological processes of the differentially expressed mRNA in CHD. Methods The R language was used to screen the differentially expressed exosomal genes in the peripheral blood of CHD, and the online databases and Cytoscape software was used to construct the CeRNA networks.And then visualized and analyzed the key genes. In the end, the GO and KEGG enrichment analysis was performed for the differentially expressed mRNA key genes. Results A total of 312 exosomal mRNA, 43 exosomal lncRNA and 85 exosomal circRNA with differential expressed were screened out from the peripheral blood of CHD patients. Through the construction of the CeRNA network, it was found that mRNA, lncRNA and circRNA competitively bound to miRNA, and the expressions of lncRNA combined with miRNA were significantly up-regulated, while the expressions of mRNA and circRNA were mostly significantly down-regulated. The GO and KEGG enrichment analysis of key genes of differentially expressed mRNA showed that these key genes were mainly related to “phosphatase activator activity” and “phosphatase regulatory activity” functions. Conclusions The peripheral blood exosomes screened by exoRBase database in patients with CHD are significantly different from those in healthy people, and mRNA, lncRNA and circRNA can competitively combine with miRNA significantly related to CHD and achieve mutual regulation. These genes may be involved in the occurrence and development of CHD and can be used as its regulatory points and therapeutic drug targets.

Abstract:Aim To investigate the effect of saikosaponin A on oxidative stress and ferroptosis of human umbilical vein endothelial cells (HUVEC) induced by hydrogen peroxide (H₂O₂). Methods The oxidative injury model in HUVEC was established and cells were divided into control group, model group, saikosaponin A low-dose, medium-dose and high-dose groups. CCK-8 assay was used to detect cell viability. The levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) were detected by the kit assay. qRT-PCR was used to detect the mRNA levels of glutathione peroxidase 4(GPX4) and acyl-CoA synthetase long chain family member 4(ACSL4). The protein expression of GPX4 and ACSL4 were detected by Western blot. Results Compared with the control group, the survival rate of HUVEC, GSH level and SOD activity in H₂O₂ group were significantly decreased (P＜0.05), the level of MDA was significantly increased (P＜0.05), the expressions of GPX4 mRNA and protein were significantly decreased (P＜0.05), the expressions of ACSL4 mRNA and protein were increased (P＜0.05). Compared with the model group, saikosaponin A dose-dependently increased the survival rate of HUVEC, inhibited oxidative stress, improved the activity of SOD and GSH level (P＜0.05), and decreased the level of MDA (P＜0.05); In addition, saikosaponin A inhibited ferroptosis in a concentration-dependent manner, up-regulated the expression of GPX4 mRNA and protein(P＜0.05), and decreased the expression of ACSL4 mRNA and protein (P＜0.05). Conclusion Saikosaponin A can protect HUVEC from oxidative stress and ferroptosis induced by H₂O₂.

Abstract:Aim To investigate the imaging type distribution and clinical characteristics of magnetic resonance imaging (MRI) in patients with internal watershed cerebral infarction (IWSI). Methods The clinical data of 98 patients with IWSI admitted between June 2017 and December 2018 were retrospectively analyzed. All patients underwent MRI and diffusion-weighted imaging (DWI). The MRI imaging type distribution and clinical characteristics were evaluated among patients with IWSI, and the clinical efficacy (National Institutes of Health Stroke Scale (NIHSS)) and prognosis and outcomes (Modified Rankin Scale (mRS)) were evaluated among the patients. Results The fusion type showed periventricular cigar-like lesions, 44 cases (44/8,4.90%) in total. The focal type showed single quasi-circular lesions, 37 cases (37/8,7.76%) in total. Beaded type presented as multiple bead-like lesions in brain watershed area, 17 cases (17/8,7.35%) in total. T1WI sequence of patients with IWSI showed low signal, and T2WI sequence showed high signal change, and T1WI sequence low signal in some patients with hemorrhagic cerebral infarction showed a high signal change. The proportion of combination of cortical watershed cerebral infarction (CWSI) of fusion IWSI was higher than that of focal and beaded IWSI (P＜0.05), and the proportion of moderate or above middle cerebral artery stenosis of fusion IWSI was less than that of focal and beaded IWSI (P＜0.05). The occurrence of plaques and the proportion of unstable plaques of focal IWSI were significantly lower than those of fusion and beaded IWSI (P＜0.05). There were no statistically significant differences in the NIHSS scores at admission, improvement rate and mRS scores at 6 months of follow-up among different types of IWSI (P＞0.05), and the NIHSS scores at 1week after admission of focal IWSI was lower than that of patients with fusion and beaded IWSI (P＜0.05). Conclusions Patients with fusion IWSI have the highest proportion, and there are differences in the clinical characteristics among different imaging types. Fusion IWSI is more likely to be complicated with CWSI and has a higher middle cerebral artery stenosis. Clinical diagnosis of IWSI can be made based on MRI results.

Abstract:Aim To investigate the relationship between serum transforming growth factor β1 (TGF-β1), soluble suppression of tumorigenicity-2 (sST2) and the length and severity of thoracic aortic aneurysm (TAA), and to analyze the diagnostic value of serum TGF-β1 and sST2 in the diagnosis of TAA. Methods A total of 72 TAA patients (TAA group) admitted to West China Guang'an Affiliated Hospital of Sichuan University from July 2018 to December 2020 and 77 healthy volunteers (control group) were selected. Serum levels of TGF-β1, sST2, inflammatory factors and fibrosis indexes were detected. The lesion length and lesion degree of TAA were measured by echocardiography. Pearson or Spearman correlation coefficient was used to describe the correlation between TGF-β1, sST2 and lesion length, lesion degree, inflammatory factors, fibrosis indexes. Logistic regression was used to analyze the risk factors of TAA and the value of TGF-β1 and sST2 in the diagnosis of TAA was analyzed by receiver operating characteristic (ROC) curve. ResultsThe levels of serum TGF-β1 and sST2 were higher in TAA group than those in control group (t＝18.0,7.534, P＜0.05). Serum TGF-β1 and sST2 levels were positively correlated with the length of thoracic aortic lesion, the degree of thoracic aortic lesion, interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-33(IL-33), hyaluronic acid(HA), type Ⅲ procollagen(PCⅢ), type Ⅳ collagen, Ⅳ-C), and laminin(LN) (r/r_s＝0.751～0.921, P＜0.05). High levels of IL-33 (OR(95%CI)＝1.250(1.062～1.471)), PCⅢ(OR (95%CI)＝1.390(1.131～1.707)), Ⅳ-C(OR(95%CI)＝1.141(1.005～1.296)), TGF-β1(OR(95%CI)＝2.447 (1.370～4.372)) and sST2 (OR(95%CI)＝1.749 (1.327～2.306)) were risk factors for TAA (P＜0.05). The area under curve (AUC) of combined TGF-β1 and sST2 for diagnosis of TAA was 0.826, which was higher than that of TGF-β1 and sST2 alone (P＜0.05). Conclusion The increase of serum TGF-β1 and sST2 levels is associated with the occurrence of TAA, the length and degree of TAA lesion, and can be used as a potential indicator for the evaluation of TAA disease.

Abstract:Aim To investigate the risk factors of in-stent restenosis (ISR) within 2 years after the implantation of drug-eluting stent (DES) in patients with coronary heart disease and type 2 diabetes, and construct a Nomogram prediction model. Methods Clinical data of patients with coronary heart disease and type 2 diabetes who received DES at the Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen from January 2010 to February 2020 were retrospectively analyzed. The PASS estimation model generates cohort sample size, which was divided into ISR group (DES-ISR) and non-ISR (non-DES-ISR) group based on the results of coronary angiography. The single factor and conditional multivariate Logistic regression analysis were performed on the parameters with statistical significance between the two groups, and the Nomogram prediction model was constructed and its reliability was verified in the validation cohort. Results A total of 1 741 cases were included in model generated cohort, 233 cases (13.4%) were diagnosed with ISR within 2 years after implantation of DES. Conditional multivariate Logistic regression analysis showed that the predictor of DES-ISR was estimated glomerular filtration rate (eGFR)＜60 mL/(min·1.73 m²) (OR＝2.7,5%CI:1.41～5.47, P＝0.003), dyslipidemia (OR＝1.0,5%CI:1.30～2.78, P＝0.001), fasting blood glucose (FPG) ≥6.5 mmol/L (OR＝5.0,5%CI:3.05～9.92, P＜0.001), multivessel coronary artery disease (OR＝7.6,5%CI:3.27～16.11, P＜0.001), diffuse coronary artery disease (OR＝1.0,5%CI:1.13～2.88, P＝0.014), primary PCI operation time ≥60 min (OR＝2.2,5%CI:1.13～6.05, P＝0.024) and emergency PCI (OR＝2.0,5%CI:1.48～3.28, P＜0.001). The model validation cohort contained 102 cases, the risk of DES-ISR increased with the increase of the Nomogram scores. The area under the receiver operating characteristic (ROC) curve of the Nomogram model was 0.791 (95%CI:0.753～0.829, P＝0.019). Conclusions The anatomical characteristics of coronary artery and PCI procedures are important predictors of DES-ISR. Nomogram can effectively identify high-risk groups of DES-ISR and provide effective decision-making information for follow-up and intervention of high-risk groups.

Abstract:Aim To investigate the correlation between triglyceride/high density lipoprotein cholesterol ratio (TG/HDLC) and carotid plaque instability in patients with ischemic stroke (IS). Methods 594 patients with acute IS treated in the Department of Neurology of Baoding First Central Hospital from January 2019 to January 2020 were included retrospectively. All subjects underwent ultrasound examination to understand the carotid plaque. According to the ultrasound results, the subjects were divided into non-plaque group (105 cases), stable plaque group (63 cases) and unstable plaque group (426 cases). The routine biochemical indexes and blood lipid indexes were detected by automatic biochemical analyzer, and the differences of risk factors, biochemical indexes and blood lipid were compared in each group. Logistic regression analysis was used to evaluate the influencing factors of carotid plaque instability, and the odds ratio (OR) and 95% confidence interval (95%CI) were calculated. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of TG/HDLC for carotid plaque instability. Results Among the 594 patients with IS, 105 had no carotid stenosis and 489 had carotid stenosis, including 439 cases of mild stenosis, 20 cases of moderate stenosis, and 30 cases of severe stenosis. The male, body mass index (BMI), smoking history, drinking history, hemoglobin, TG/HDLC in unstable plaque group were higher than those in stable plaque group, and age, HDLC were lower than that in stable plaque group (P＜0.05). Multivariate Logistic regression analysis showed that TG/HDLC was an independent risk factor for carotid plaque instability (OR 1.8,5%CI 1.027～2.551, P＝0.038). ROC curve analysis showed that the area under the curve of TG/HDLC for predicting carotid plaque instability was 0.619 (95%CI 0.542～0.696), the best cut-off value was 1.60, the sensitivity was 35.4%, and the specificity was 84.1%. Conclusion TG/HDLC is an independent risk factor for carotid plaque instability in patients with IS, and it has a certain predictive value for carotid plaque instability.

Abstract:Atherosclerosis (As) is the pathological basis of a variety of common chronic cardiovascular and cerebrovascular diseases, which begins with the destruction of the natural barrier formed by the vascular endothelial cells. The main manifestations can change the signal transduction and related inflammatory gene expression of Caspase-1/Sirt1/AP-1, SREBP2/NOX2/NLRP3, KLF2/FoxP1/NLRP3, NFAT5/NLRP3 and thus activating endothelial cells. Then, monocytes infiltrate into the intima of aortic wall and differentiate into macrophages, resulting in an innate immune response in response to endothelial activation. Firstly, cholesterol crystallization in macrophages activates NLRP3/ASC/Caspase-1 inflammatory body pathway under the synergistic effect of other regulatory signals. It can increase the release of pro-inflammatory cytokines IL-1β and IL-18, mediate the expression of downstream inflammatory factors and chemokines, and promote the inflammatory response of As. Sustained chronic inflammatory reaction in vascular wall can change the phenotype of vascular smooth muscle cells, promote the formation of as plaque, change the composition of plaque and increase the vulnerability. Plaque microcalcification also increases the vascular stress at the plaque, with consequences that the risk of rupture is increased. In this paper, the research status of inflammatory mechanism of As, mediated by innate immune, can provide ideas for the development of anti-inflammatory drugs and promote the experimental design of anti-inflammatory research.

Abstract:Structural vascular imaging throughout the body has advanced rapidly, and the atherosclerotic stenosis and plaque could be visualized as well as qualitatively and quantitively assessed. Multimodality imaging can improve cardiovascular and cerebral risk prediction by informing on the constituency and metabolic processes within the vessel wall. This review will provide an overview of current imaging techniques for the imaging of atherosclerotic disease.

Abstract:Cardiovascular disease is the leading cause of death. Moreover, the incidence of cardiovascular disease in young/middle-aged people (18~45 years old) is still on the rise. Early diagnosis, early warning and treatment of cardiovascular disease are important topics in the current medical research field. Atherosclerosis is the pathophysiological basis of many cardiovascular diseases. Recent studies have shown that the tricarboxylic acid (TCA) cycle intermediate is involved in the occurrence and development of atherosclerosis, and considered as the early diagnosis and warning bio-markers for atherosclerosis. Here, the roles and underlying mechanisms of succinate in the initiation and progression in atherosclerosis were reviewed.

Abstract:Ischemic stroke is the most common type of stroke, and its disability rate is very high, which can lead to death in severe cases. Biomarkers can accelerate the definite diagnosis, which is very important to guide doctors to choose effective treatment methods. In recent years, the correlation between ischemic stroke and amino acid metabolism has attracted extensive attention. Studies have found that there are significant changes in amino acid metabolites and metabolic pathways after stroke, and some amino acids may be potential biomarkers. This article mainly reviews the changes of different types of amino acid metabolism in patients with ischemic stroke, in order to provide reference for exploring biomarkers and pathogenesis of ischemic stroke, so as to open up a new direction for its diagnosis, treatment and prevention.