Abstract:Obesity is a chronic metabolic disease caused by a variety of factors, manifested by excessive accumulation of body fat and/or abnormal fat distribution. The main pathogenesis of atherosclerosis is lipid accumulation within the artery walls, the proliferation of smooth muscle cell and fibrous matrix, and development of atherosclerosis plaques. A large number of basic and clinical studies have shown that obesity is a well-established risk factor for atherosclerosis, and its potential mechanisms include abnormal lipid metabolism, insulin resistance, inflammation, and endothelial dysfunction.However, the mechanistic link between accumulation of adipose tissue and development of atherosclerosis is not clear. This article will focus on the opinions of epicardial adipose tissue and perivascular adipose tissue, new adipokines, adipose-derived exosomes, and adipose browning, in order to state the impact of obesity on atherosclerosis and to provide a new perspective for the study of intervention strategies for atherosclerosis.

Abstract:Aim To observe the effect of palmitic acid (PA) on inflammatory response of endothelial cell line EA.hy926 in vitro, and to detect the expression of related genes and explore their possible signaling pathways. Methods Endothelial cell line EA.hy926 was cultured in vitro and divided into albumin control group and PA intervention group. The effect of PA incubation on EA.hy926 cell viability was detected by modified MTT assay. mRNA of interleukin-1(IL-1), interleukin-6(IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and monocyte chemotactic protein 1(MCP-1) were detected by real-time fluorescence quantitative PCR. The levels of IL-6, IL-8 and TNF-α were detected by ELISA, and the levels of phosphorylated nuclear factor-κB (NF-κB) p65, NF-κB p65 and nuclear factor-kappa B inhibitor protein (IκBα) were detected by Western blot. Results Compared with the albumin control group, the mRNA levels of IL-1, IL-6 and IL-8 in PA (20 μmol/L, 50 μmol/L, 100 μmol/L) intervention group significantly increased (P<0.05). The mRNA levels of TNF-α and MCP-1 in PA (50 μmol/L, 100 μmol/L) intervention group significantly increased (P<0.05). The levels of IL-6, IL-8 and TNF-α in supernatant increased significantly (P<0.05), the level of IκBα protein decreased significantly (P<0.05), and the phosphorylation level of NF-kappa B p65 increased significantly (P<0.05). Conclusion PA intervention induces inflammatory response in EA.hy926 cells, which may be related to activation of NF-kappa B signaling pathway.

Abstract:Aim To investigate whether modified Zhishi Xiebai Guizhi decoction activates MitoKATP channel during myocardial ischemia-reperfusion to produce mitochondrial protection, thereby inhibiting mitochondrial apoptosis pathway and alleviating myocardial ischemia-reperfusion injury. Methods Twenty-four Sprague-Dawley rats were randomly divided into 3 groups:sham operation group (n=6), ischemia reperfusion model group (IR group, n=9), modified Zhishi Xiebai Guizhi decoction group (M group, n=9). After 14 days of administration, coronary artery anterior descending was performed. The model was established, and the ST segment of myocardial electrocardiogram, myocardial enzyme (CK-MB, LDH) and mitochondrial ultrastructural changes were observed. The myocardial infarct size of IR group and M group was compared by Evans blue/TTC staining. After rhodamine 123 staining, the mitochondrial membrane potential was detected by flow cytometry. The expressions of connexin43 (Cx43), protein kinase C-ε (PKC-ε) and inward-rectifier potassium channel 6.2 (Kir6.2) subunits in mitochondria of each group were detected by Western blot. Methylthymol blue microplate assay was used to detect calcium content in mitochondria of rats in each group. Results Modified Zhishi Xiebai Guizhi decoction can effectively alleviate ST segment and myocardial enzyme changes caused by myocardial ischemia-reperfusion, reduce myocardial infarct size, reduce mitochondrial ultrastructure and membrane potential changes, enhance the expression of Cx43, PKC-ε and Kir6.2 in mitochondrial and mitigating mitochondrial calcium overload. Conclusion Modified Zhishi Xiebai Guizhi decoction can activate MitoKATP channel to activate mitochondrial protective effect by up-regulating the expression of Cx43 and PKC-ε in mitochondria, thereby reducing the release of cytochrome C from mitochondria, inhibiting the cascade response of caspase-related proteins to reduce myocardial cells apoptosis rate, and to reduce myocardial ischemia-reperfusion injury.

Abstract:Aim To study the regulatory effect and molecular mechanism of berberine preconditioning on inflammation and apoptosis during cerebral ischemia reperfusion (I/R) in rats. Methods 40 SPF-grade adult male SD rats were randomly divided into sham group, I/R group, berberine pretreatment group (BP group), BP+SIRT1 inhibitor EX527 group (BP+EX group). Berberine 100 mg/(kg·d) was intragastrically administered to BP group for 14 days, berberine 100 mg/(kg·d) was intragastrically administered and SIRT1 inhibitor EX527 5 mg/(kg·d) as intraperitoneally administered to BP+EX group before modeling. After 14 days, the brain I/R model was established by thread embolization. Neurological impairment score, TUNEL staining and Nissl staining were used to evaluate the degree of neurological impairment. The expression of SIRT1 pathway genes, mitochondrial pathway apoptotic genes and inflammatory factors were detected. Results The neurological deficit score, TUNEL positive rate and the expression levels of nuclear factor kappa B (NF-κB), P53, Bax, Caspase-9, Caspase-3, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), IL-6, intercellular adhesion molecule -1 (ICAM-1) in brain tissue of I/R group were significantly higher than those in Sham group, the number of positive Nissl and the expression levels of SIRT1, Bcl-xL in brain tissue were significantly lower than those in Sham group(P<0.05). The neurological deficit score, TUNEL positive rate and the expression levels of NF-κB, P53, Bax, Caspase-9, Caspase-3, TNF-α, IL-1β, IL-6, ICAM-1 in brain tissue of BP group were significantly lower than those in I/R group, the number of positive Nissl and the expression levels of SIRT1, Bcl-xL in brain tissue of BP group were significantly higher than those in I/R group (P<0.05). The expression levels of Bax, Caspase-9, Caspase-3, TNF-α, IL-1β, IL-6, ICAM-1 in brain tissue of BP+EX group were significantly higher than those in BP group, the expression levels of Bcl-xL in brain tissue of BP+EX group was significantly lower than those in BP group(P<0.05). Conclusion Berberine preconditioning can alleviate inflammation and apoptosis in rats during cerebral ischemia-reperfusion by activating SIRT1 pathway.

Abstract:Aim To investigate the effect of leonurine on the pathological changes of cerebral tissue in rats with ischemic stroke based on PI3K/AKT/NF-κB signaling pathway. Methods The rat model of ischemic stroke was established, and leonurine was administered continuously for 7 days. The neurological impairment score of each group was observed. The content of oxidative stress index was detected in rat brain tissue. The percentage of cerebral infarction area in rats was detected by TTC staining. HE staining was used to observe the pathological changes in cortex and hippocampus of rat brain. The expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducibal factor 1α (Hif-1α) in cerebral infarction cortex of rats were measured by real-time fluorescence quantitative polymerase chain reaction. Western blot was used to detect the protein expressions of phosphatidyl inositol-3-kinase (PI3K), serine-threonine protein kinase (AKT) and nuclear factor-κB (NF-kappa B) in brain tissue. Results Compared with the blank control group, the neurological impairment score, the contents of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS), mRNA expressions of VEGF and Hif-1α and protein expression of NF-κB were increased significantly, the contents of oxidized low density lipoprotein (ox-LDL) and superoxide dismutase (SOD), and protein expressions of AKT and PI3K were decreased significantly in rats of model control group; The differences had statistical significance (P＜0.01). Compared with the model control group, the neurological impairment score, the contents of NO and eNOS, mRNA expressions of VEGF and Hif-1α and protein expression of NF-κB were decreased significantly, the contents of ox-LDL and SOD, and protein expressions of AKT and PI3K were increased significantly in rats of positive control group and middle- and high-dose leonurine group; The differences had statistical significance (P＜0.01). Conclusions Leonurine has brain protective effect on rats with experimental brain injury. It can improve nerve injury after cerebral infarction, reduce the volume of cerebral infarction and reduce oxidative stress response. These effects may be achieved through PI3K/AKT/NF-κB signaling pathway.

Abstract:Aim To investigate the regulatory effects of Genipin on mitochondrial pathway apoptosis induced by ischemia and its mechanisms. Methods H9c2 cells were cultured and grouped. The control group was cultured with DMEM without drugs under normal oxygen condition, the hypoxia group was cultured with DMEM without drugs under hypoxia condition, the Genipin group was treated with DMEM containing 2.5 μmol/L, 5.0 μmol/L, 10.0 μmol/L Genipin under hypoxia condition, the NC inhibitor group was transfected with NC inhibitor under normal oxygen condition, and the NC inhibitor+hypoxia group was transfected with NC inhibitor under hypoxic conditions, NC inhibitors+hypoxia+Genipin group was transfected with NC inhibitor and treated with DMEM containing 10.0 μmol/L Genipin under hypoxic conditions, miR-499 inhibitor+hypoxia+Genipin group was transfected with miR-499 inhibitor and treated with DMEM containing 10.0 μmol/L Genipin under hypoxic conditions. The differences of myocardial enzyme content, apoptotic rate, expression of apoptotic gene and miR-499 among groups were compared. Results Genipin group could decrease lactate dehydrogenase (LDH), creatine phosphate kinase (CK), creatine phosphate kinase isoenzymes (CK-MB) contents in cell culture medium, cell apoptotic rate, Bax and caspase-3 expression in cells, and increased the expression of Bcl-xL and miR-499 in cells in a dose-dependent manner. Transfection with miR-499 inhibitors could reverse 10.0 μmol/L Genipin reducing LDH, CK, CK-MB content in cell culture medium, apoptotic rate, Bax and caspase-3 expression and increasing Bcl-xL expression. Conclusion Genipin regulates mitochondrial apoptosis induced by ischemia and hypoxia via miR-499.

Abstract:Aim To investigate the correlation between monocyte to lymphocyte ratio (MLR) and lesion severity of coronary artery in patients with coronary heart disease (CHD) and its predictive value. Methods 203 patients with coronary angiography in the Department of Cardiology of Huayuan Mountain Branch of Hubei Provincial Hospital of Traditional Chinese Medicine from January to December 2018 were selected as the study subjects. 161 patients with CHD were divided into mild lesion group, moderate lesion group and severe lesion group according to the severity of coronary artery lesion (Gensini score). 161 patients with CHD were further divided into three groups according to the MLR three-quantile.In 42 cases of control group, coronary angiography showed that the normal coronary or stenosis degree of coronary artery was less than 50%. Logistic stepwise regression and receiver operating characteristic curve (ROC) were used to analyze the correlation between MLR and lesion severity of coronary artery in CHD patients and its predictive value. Results (1)Inter-group comparison of MLR three-quantile, coronary artery lesion score in the second three-quantile group and third three-quantile group was significantly higher than that in the first three-quantile group (P＝0.022, P＝0.001). (2)Spearman correlation analysis showed that MLR level was positively correlated with the severity of coronary artery lesions in CHD patients (r＝0.281, P＜0.01); Kendall correlation analysis also showed a positive correlation between MLR level and the severity of coronary artery lesions in CHD patients (r＝0.188, P＜0.01). (3)Logistic stepwise regression analysis showed that smoking history, old age, MLR and apolipoprotein B were independent risk factors for CHD, while apolipoprotein A1 was a protective factor for CHD. (4)ROC curve analysis showed that the area under curve of MLR was 0.709 (95%CI:0.621-0.797). When the cut-off value of MLR was 0.186, the diagnostic efficacy of MLR for CHD was the highest, with a sensitivity of 82.6% and a specificity of 50.0%. Conclusions Inflammation plays an important role in the pathogenesis of CHD. As an independent risk factor, MLR has predictive value for CHD.

Abstract:Aim To evaluate the association between left ventricular end-diastolic pressure (LVEDP) and contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention (PCI). Methods Single center clinical data of patients who underwent PCI were retrospectively analysed to explore the predictive value of LVEDP for the occurrence of CIN. Results Among 1 301 patients who underwent PCI during the study period, 125 patients (9.61%) developed CIN. Risk factors for CIN included age, female, chronic kidney disease, history of diabetes mellitus, anemia, heart failure and emergencies in our study cohort. Compared with non-CIN group, the average LVEDP was higher in patients with CIN after PCI ((18.4±8.7) mmHg vs (14.4±6.6) mmHg, P<0.001). Multiple regression analysis showed that LVEDP (≥20 mmHg) could independently predict the occurrence of CIN (OR 1.6,5%CI 1.08～1.47). The predictive value of LVEDP for CIN was enhanced in patients with low ejection fraction. Contrast dosage in high-risk patients determined by elevated LVEDP was comparable to that in patients not found. Conclusions LVEDP is an independent predictor for CIN. Patients with elevated LVEDP (≥20 mmHg) are at higher risk of CIN after PCI. In CIN prevention, high-risk patients defined by elevated LVEDP need to be noticed by clinicians.

Abstract:Aim To investigate the distribution of red blood cell distribution width (RDW) and mean platelet volume (MPV) in patients with premature coronary artery disease(PCHD) and its relationship with the severity of PCHD, and to evaluate the diagnostic value of RDW and MPV for PCHD. Methods A total of 407 patients with suspected coronary artery disease(CHD) due to chest pain and male <55 years old and female <65 years old were enrolled in the study. All patients received coronary angiography (CAG), 309 cases of PCHD were confirmed and the remaining 98 cases were normal control group. The levels of RDW and MPV in the two groups and the subgroups of the PCHD were compared. The correlation between RDW and MPV and severity of coronary lesions (Gensini score) and independent risk factors for PCHD were analyzed. Results The levels of RDW and MPV in the PCHD group were significantly higher than those in the control group (P<0.05). RDW and MPV were higher in the acute myocardial infarction (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP) groups than the control group (P<0.05); there was a positive correlation between RDW, MPV and Gensini scores in the PCHD group(r=0.246 and 0.199, P<0.05). Multivariate Logistic regression analysis showed that RDW and MPV were independent risk factors for PCHD(OR=3.3,5%CI:2.197~6.359, P<0.001; OR=1.3,5%CI:1.074~1.705, P=0.010). R0C curve analysis showed that the optimal cut-off value of RDW to diagnose PCHD was 12.25% with a sensitivity of 69% and specificity of 72%, and the optimal cut-off value of MPV to diagnose PCHD was 8.55 fl with a sensitivity of 91% and a specificity of 37%. Conclusions RDW and MPV are correlated to the clinical type of PCHD and the severity of PCHD. RDW and MPV are the independent risk factors for PCHD, which provides some value for the diagnosis of PCHD.

Abstract:Aim To investigate the relationship between homocysteine levels and dyslipidemia in patients with hyperhomocysteinemia. Methods A retrospective study was conducted on the data of 58 297 physical examiners who were admitted to a medical examination institution in a city in northern China from February 2017 to December 2017. The chi-square test was used to analyze the difference of homocysteine levels in physical examiners, and logistic regression analysis was performed to control the effects of age, gender and body mass index (BMI) on the outcome. Results Logistic regression analysis showed that male (OR=3.1,5%CI:3.265～4.564) and impaired fasting glucose (OR=1.2,5%CI:1.034～1.639) were risk factors for hyperhomocysteine. And with the increase of apolipoprotein AⅠ, the risk of hyperhomocysteinemia decreased (OR=0.2,5%CI:0.515～0.904). Conclusions Homocysteine levels may be associated with hyperlipidemia, especially for hypertriglyceridemia. And the risk of hyperhomocysteinemia decreases with the increase of apolipoprotein AⅠ.

Abstract:Aim To study the relationship between apolipoprotein E gene polymorphism and coronary heart disease in women. Methods Apolipoprotein E, female coronary heart disease, and gene polymorphism were used as the search terms, and Wanfang, CNKI, Chinese biomedical literature, SpringerLink database and PubMed database were searched from foundation September 0,8. Alleles E2 and E4 were compared with E3, and genotypes E2/2, E2/3, E2/4, E3/4 and E4/4 were compared with E3/3, respectively. Statistical software Stata14.0 was used for Meta analysis of all data, and combined odds ratio (OR value) and 95% confidence interval (95%CI) were used to describe the counting data. The heterogeneity analysis process was completed with I², and it was considered that there was significant heterogeneity when P<0.1 or I²>50%. Publication bias was analyzed using funnel plot. The reliability of the results was assessed by sensitivity analysis. P<0.05 was considered statistically significant. Results A total of 940 related literatures were retrieved, and 9 literatures were finally included. One in Chinese and eight in English. The selected literatures were all case-control studies, and the literatures were evaluated by NOS quality score scale. The selected literatures were all higher than 5 points, which was considered as high-quality literatures. Meta analysis results of selected literature showed that genotype E2/2(OR 4.5,5%CI (1.2,1.19)), E3/4(OR 1.8,5%CI (1.0,2.82)), E4/4(OR 4.5,5%CI (2.6,9.60)) were significantly higher in the case group than in the control group, E2/3(OR 1.0,5%CI (0.9,1.54)), E2/4(OR 1.3,5%CI (0.1,2.07)) had no statistical significance in the incidence of female coronary heart disease. Conclusion The risk of coronary heart disease increased significantly in women with the genotype E2/2, E3/4 and E4/4.

Abstract:Myocardial ischemia, hypoxia and necrosis after myocardial infarction lead to a multiphase repair process in which damaged tissue is replaced with fibrous scars produced by fibroblasts and myofibroblasts. Non-infarct ventricular wall reactive remodeling, including interstitial and perivascular fibrosis, leads to changes in ventricular wall geometry, biomechanics, biochemistry and so on. Although initial repair fibrosis is essential to prevent ventricular wall rupture, excessive fibrosis leads to progressive damage to heart function and eventually to heart failure. Recent studies have shown that the heart has plasticity, restoring impaired cardiac function, and promoting myocardial repair after infarction are important targets for the treatment of cardiovascular diseases. To this end, people continue to explore new therapies, regeneration therapy for myocardial infarction treatment has brought new hope. This review summarizes the current myocardial infarction repair and reaction mechanism of cardiacl fibrosis, to explore the potential of inducing fibroblasts and myofibroblasts into cardiomtocytes, and review the currently available and potential future therapeutic strategies to inhibit cardiac fibrosis.

Abstract:Coronary atherosclerotic heart disease and ischemic stroke are the two main diseases of atherosclerotic diseases. They can occur alone or in combination, and are important causes of death and functional deficiency. There are some common risk factors in the two diseases, which are related to the occurrence of the disease. To clarify the correlation between the two diseases is helpful to the prevention and treatment of atherosclerotic diseases, relieving the burden of adverse prognosis and improving the quality of life of the people. At present, many studies have been devoted to exploring the relationship between the two diseases in pathogenesis, disease progression, prognosis and imaging manifestations, among which some results are different. The latest research results are summarized as follows.

Abstract:Aortic dissection (AD) is a serious cardiovascular disease with high mortality rate. It has the characteristics of rapid onset, rapid progress, complex and diverse manifestations, dangerous course, high mortality and poor prognosis. Although the specific pathogenesis of AD has not been fully elucidated, in recent years, microRNA (miRNA) has been found to play an important role in the occurrence and development of many cardiovascular diseases. Through the application of gene chip technology analysis and other related studies, it is found that there are significant differences in the expression of some microRNAs between AD patients and normal aortic tissues, which obviously contribute to the diagnosis of AD. Many studies have shown that miRNAs may play an important role in the pathogenesis and diagnosis of AD. This article reviews the research progress on differential expression and pathogenesis of miRNAs in AD.

Abstract:Neutrophil gelatinase-associated lipocalin (NGAL), also known as Lcn2 (lipocalin 2), or oncogene 24p3, is a gelatinase complex stored in mature neutrophil-specific particles. Glycoproteins are also produced by other cell types, including cardiomyocytes. NGAL is an early biomarker of acute kidney injury. Recently, NGAL has been found to be an independent predictor of major adverse cardiovascular events and mortality, but the relationship between NGAL and cardiovascular disease (CVD) has not been agreed. This article reviews the relationship between NGAL and coronary heart disease, hypertension and heart failure, and the targeted therapy of NGAL and CVD.