Abstract:Atherosclerosis (As) is a chronic inflammatory disease, which is the common pathological basis of many cardiovascular and cerebrovascular diseases. But the pathological procedure involved is complicated, and the molecular mechanism is still unclear. In recent years, microarray, proteomics, High-throughput sequencing and metabolomics are used widely, helping us further understand the molecular mechanism. At the same time, the rapid development of bioinformatics largely speeds up the requirement and analysis of biomedical data. Among this, the pathogenesis of atherosclerosis is gradually recognized, including atherosclerosis genomics, proteomics, metabonomic and drug target prediction and so on. This revealed that inflammation, immunity, oxidative phosphorylation, lipid metabolism and energy dysfunction were highly correlated with the pathogenesis of atherosclerosis. This review will discuss the applications of bioinformatics in As.

Abstract:Aim To investigate the role of Notch pathway in the anti-atherosclerotic effect of angiotensin-(1-7) (Ang-(1-7)). Methods Oxidized low density lipoprotein (ox-LDL) was used to induce macrophages to foam cells.At first, 10－7 mmol/L Ang-(1-7) and 10－5 mmol/L A-779 were pre-cultured with macrophages before ox-LDL administered solely or together in Ang-(1-7) group and A-779 group. Notch ligands, receptors and downstream product Hes1 were assayed by qRT-PCR and Western blot. Second, delta-like (Dll) 4.Fc was co-cultured with macrophages to activate Notch pathway, toll like receptor-4 (TLR-4), nuclear factor kappaB (NF-κB) and iNOS mRNA and protein were assayed by qRT-PCR and Western blot, proinflammatory cytokines interleukin 1beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) were assayed by using ELISA. Results Notch1, Notch2 and Dll1 mRNA levels were significantly decreased in ox-LDL group, whereas elevated in Ang-(1-7) group (P＜0.05). Meanwhile, Notch3, Notch4, Dll4 and Jagged2 mRNA levels were significantly increased in ox-LDL group, while reduced in Ang-(1-7) group (P＜0.05). There was no difference in Dll3 and Jagged1 mRNA levels between ox-LDL group and Ang-(1-7) group (P＞0.05). The downstream product of Notch pathway gene Hes1 was significantly activated by ox-LDL (P＜0.05), while decreased by Ang-(1-7) administrated (P＜0.05). Using Dll4.Fc to activate Notch pathway could increase the expressive levels of Hes1 and TLR-4, promote translocation of NF-κB from cytoplasm to nucleus, and stimulate inflammatory cytokines IL-1β, IL-6 and TNF-α secretion (P＜0.05). Ang-(1-7) could rescue this alternation significantly (P＜0.05). Co-treatment with A-779 can reverse the effect partially (P＜0.05). Conclusion Ang-(1-7) could alleviate TLR-4/NF-κB-induced inflammatory cytokines secretion in macrophages via regulating Dll4-associated pathway.

Abstract:Aim To investigate the protective effects of quercetin on H9c2 cells injury induced by nutritional deprivation, and observe its effect on adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signalling pathway. Methods H9c2 cells were cultured in vitro and divided into five groups:control group, nutritional stress group (NS group), quercetin group (NS+Qu group), compound C group (NS+CC group), and quercetin+compound C group (NS+CC+Qu group). The viability of H9c2 cells was determined by CCK8 assay and Hoechst staining. The apoptosis and mitochondrial membrane potentials of H9c2 cells were measured using flow cytometry. ATP content in H9c2 cells were observed. Western blot was used to detect the expression levels of Cleaved caspase-3, PTEN induced putative kinase 1 (PINK1), mitofusin2 (MFN2) and p-AMPK in H9c2 cells. Results Compared with control group, the viability of H9c2 cells in NS group was significantly decreased (P<0.05), the apoptotic rate and Cleaved caspase-3 expression were greatly increased (P<0.05), ATP level, mitochondrial membrane potentials (AMRE) and PINK1 expression were significantly decreased (P<0.05). Compared with NS group, the viability of H9c2 cells in NS+Qu group was significantly increased (P<0.05), the apoptotic rate and Cleaved caspase-3 expression were greatly decreased (P<0.05), ATP level, mitochondrial membrane potentials (AMRE) and PINK1 expression were significantly increased (P<0.05). Compared with NS+Qu group, the viability of H9c2 cells and p-AMPK expression level in NS+CC+Qu group was significantly decreased (P<0.05). Conclusion Quercetin can improve the injury of H9c2 cells via regulating AMPK signaling pathway.

Abstract:Aim To observe the inhibition effect of oxysophoridine (OSR) on myocardial cell apoptosis after acute myocardial infarction (AMI) in rats through nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) pathway. Methods Adult healthy male SD rats were divided into sham-operated group (Sham group), AMI group, OSR group, OSR＋zinc protoporphyrin (ZPP-Ⅸ) group. The left anterior descending coronary artery ligation was used to establish the AMI model in the latter three groups. OSR was intraperitoneally injected into OSR group, OSR and HO-1 inhibitor ZPP-Ⅸ were intraperitoneally injected into OSR＋ZPP-Ⅸ group. The contents of serum myocardial enzymes, apoptotic rate of cardiomyocyte, expressions of apoptotic gene, Nrf2 and HO-1 in myocardium were detected. Results The serum contents of lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme MB (CK-MB), myocardial cell apoptotic rate, and the expressions of Bcl-2 associated X protein (Bax), Cleaved-caspase-3, Nrf2 and HO-1 in myocardium in AMI group were significantly higher than those in Sham group, and the expression of B-cell lymphoma-2 (Bcl-2) in myocardium was significantly lower than that in Sham group. The serum contents of LDH, CK, CK-MB, myocardial cell apoptotic rate, and the expressions of Bax and Cleaved-caspase-3 in myocardium in OSR group were significantly lower than those of AMI group, and the expressions of Bcl-2, Nrf2 and HO-1 in myocardium were significantly higher than those in AMI group. The serum contents of LDH, CK, CK-MB, myocardial cell apoptotic rate, and the expressions of Bax and Cleaved-caspase-3 in myocardium in OSR＋ZPP-Ⅸ group were significantly higher than those in OSR group, and the expression of Bcl-2 in myocardium was significantly lower than that in OSR group. Conclusion OSR can inhibit myocardial cell apoptosis after AMI by activating Nrf2/HO-1 pathway in rats.

Abstract:Aim To study the protective effect and molecular mechanism of losartan on cerebral ischemia reperfusion (IR) injury in rats. Methods 80 adult male SD rats were randomly divided into sham group, IR group, 2.5 mg/kg losartan group, 5.0 mg/kg losartan group and 5.0 mg/kg losartan＋LY group. 2.5 mg/kg losartan group, 5.0 mg/kg losartan group, 5.0 mg/kg losartan＋LY group were given losartan intragastrically for 14 days before modeling, and 5.0 mg/kg losartan＋LY group was given phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 intraventricular injection 30 minutes before modeling. The model of cerebral IR injury was established by thread embolism method. At 24 hours after reperfusion, the neurological deficit was evaluated, and the water content of brain tissue, cell apoptosis and expression of apoptosis related genes were measured. Results Compared with sham group, the brain water content, neurological deficit score, TUNEL positive rate and the levels of Bcl-2 associated X protein (Bax)/GAPDH, cytochrome C (CytC)/GAPDH, cleaved cysteinyl aspartate specific proteinase-3 (caspase-3)/pro-caspase-3 in brain tissue of rats in IR group were significantly increased, while the levels of B-cell lymphoma-2 (Bcl-2)/GAPDH, p-PI3K/PI3K, p-AKT/AKT in brain tissue were significantly decreased. Compared with IR group, the levels of the brain water content, neurological deficit score, TUNEL positive rate and the levels of Bax/GAPDH, CytC/GAPDH, cleaved-caspase-3/pro-caspase-3 in brain tissue of rats in 2.5 mg/kg losartan group, 5.0 mg/kg losartan group were significantly decreased, while the levels of Bcl-2/GAPDH, p-PI3K/PI3K, p-AKT/AKT in brain tissue were significantly increased. Compared with 5.0 mg/kg losartan group, the levels of the brain water content, neurological deficit score, TUNEL positive rate and the levels of Bax/GAPDH, CytC/GAPDH, cleaved-caspase-3/pro-caspase-3 in brain tissue of rats in 5.0 mg/kg losartan＋LY group were significantly increased, while the levels of Bcl-2/GAPDH, p-PI3K/PI3K, p-AKT/AKT in brain tissue were significantly decreased. Conclusion Losartan can alleviate cerebral IR injury by up-regulating PI3K/AKT pathway in rats.

Abstract:Aim To investigate the expression and clinical significance of Long chain non coding RNA TUG1 (LncRNA TUG1) and microRNA 138-5p(miR-138-5p) in plasma of patients with chronic heart failure(CHF). Methods The expression of LncRNA TUG1 and miR-138-5p in plasma of 148 patients with coronary heart disease complicated with chronic heart failure (CHF group) and 40 healthy persons (control group) were detected by real-time quantitative PCR. The correlation between the expression of TUG1 and miR-138-5p and clinical parameters was analyzed. ROC curves were used to analyze the potential of TUG1 and microRNA-138-5p for early diagnosis of CHF. Kaplan Meier survival analysis was used to analyze the effects of TUG1 and miR-138-5p on the 2-year survival rate of CHF. Results Compared with the control group, the expression of TUG1 and BNP in the plasma of patients with chronic heart failure was significantly higher (P<0.001), while the expression of microRNA-138-5p in the plasma of patients with chronic heart failure was significantly lower (P<0.05). The expression of TUG1 was positively correlated with the expression of BNP in serum of CHF patients (r=0.682, P<0.001), but negatively correlated with the expression of microRNA-138-5p and left ventricular ejection fraction (LVEF) (P<0.05). The area under curve (AUC) of LncRNA TUG1 as a biomarker for the diagnosis of chronic heart failure was 0.868 (95% CI 0.590~0.960, P<0.001). The area under curve (AUC) of microRNA-138-5p as a biomarker for the diagnosis of chronic heart failure was 0.607 (95% CI 0.620~0.940,P<0.001).Kaplan-Meier analysis showed that the 2-year median survival time of patients with high expression of LncRNA TUG1 was shorter than that of patients with low expression, and the difference was statistically significant (χ²=19.77, P<0.001). The median 2-year survival time of patients with high expression of microRNA-138-5p was longer than that of patients with low expression, with significant difference (χ²=11.97, P<0.001). The high expression of TUG1 in plasma of patients with chronic heart failure is related to the diagnosis and prognosis of CHF. Conclusion The high expression of TUG1 in patients with chronic heart failure is negatively correlated with the expression of miR-138-5p, which can be used as a biomarker for early diagnosis and prognosis evaluation of CHF.

Abstract:Aim To investigate the plasma expression of long non-coding RNA MALAT1 in patients with type 2 diabetes mellitus (T2DM) and its clinical significance. Methods A total of 270 patients treated were divided into 2 groups:T2DM group (n=136) and control group (n=134). Expression levels of plasma MALAT1 were measured by qRT-PCR; then the relationship was analyzed in relevant patients between MALAT1 and clinical features. Results Compared with the control group, plasma MALAT1 expression was increased in T2DM group (P<0.05). Univariate Logistic regression analysis found that plasma MALAT1, fasting blood glucose, glycosylated hemoglobin, glycosylated serum protein, lipid levels, and cystatin C (CysC) were all associated with diabetes (P<0.001). Multivariate Logistic regression analysis showed that plasma MALAT1 expression was independently associated with diabetes (P<0.05), which was 1.84 times that of the control group. Conclusion T2DM patients had obviously increased plasma level of MALAT1; MALAT1 was independently related to T2DM occurrence.

Abstract:Aim To investigate the effects of Xuezhikang (XZK) on low-density lipoprotein (LDL) subfractions and oxidized low-density lipoprotein (ox-LDL) in patients with hyperlipidemia. Methods A total of 40 subjects (20 patients with hyperlipidemia and 20 healthy subjects) who were not treated with lipid-lowering drugs were selected consecutively and divided into the XZK group (n=20) and the control group (n=20). The plasma LDL subfractions, ox-LDL were examined by using the Lipoprint system at baseline and again after 8 weeks. Results Data showed that XZK could significantly decrease not only plasma LDLC levels, total cholesterol, triglycerides, and apolipoprotein B (P＜0.05), but also ox-LDL (P＜0.05). At the same time, XZK reduced the concentration of small LDLC (P＜0.05) and the percentage of the small LDL subfraction (P＜0.05). Conclusion XZK treatment for 8 weeks significantly improved the blood lipid profile, reduced the concentration and percentage of atherogenic small LDLC, and reduced the level of oxidative stress.

Abstract:Aim To discuss the correlation between substance P precursor (Pro-SP) and platelet activation, platelet parameters. Methods A total of 76 patients were enrolled in the department of cardiology. According to the diagnostic criteria of acute myocardial infarction, the patients were divided into non-acute myocardial infarction group (n=39) and acute myocardial infarction group (n=38). Percentage of platelet-mononuclear aggregate (PMA) formation was evaluated for platelet activation by flow cytometry. The concentration of Pro-SP was determined by ELISA. The correlations of Pro-SP, PMA and the parameters of platelets were statistically compared, as well as the differences between the two groups in Pro-SP. Results Pro-SP was positively correlated with PMA (Pearson correlation coefficient 0.407, P<0.001) and platelet distribution width (Pearson correlation coefficient 0.269, P=0.018), but not with total platelet count, mean platelet volume, platelet specific volume, and large platelet ratio (P>0.05). Linear regression analysis showed that Pro-SP was an independent influencing factor of PMA, and Pro-SP was significantly higher in the acute myocardial infarction group than that in the non-acute myocardial infarction group (P<0.05). Conclusion Pro-SP is positively correlated with platelet activation and platelet distribution width, but not with total platelet count, average platelet volume, platelet specific volume, and large platelet ratio (P>0.05).

Abstract:Aim To investigate the predictive value of red blood cell distribution width (RDW) for major adverse cardiac events (MACE) in patients with acute ST segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). Methods 243 clinical cases with acute STEMI after PCI was retrospectively studied. The incidence of MACE in all patients during hospitalization were carefully recorded. The predictive value of RDW for the incidence of MACE in patients with acute STEMI after PCI was analyzed by the receiver operating characteristic(ROC) curve of RDW levels. All the patients were divided into the high RDW group and the low RDW group according to the best cut-off point we determined. The differences of baseline data, laboratory data, coronary angiography, echocardiographic tissue Doppler imaging and the incidence of MACE were compared between the two groups. Results ROC curve showed that the area under the working characteristic curve of subjects with MACE predicted by RDW was 0.634 (95%CI:0.543～0.725,P＜0.05). When the optimal cut-off point of RDW levels was 13.35%, the sensitivity of predicting MACE was 52.5%, the specificity was 68%. The rate of MACE in the high RDW group(RDW≥13.35%) was higher than in the low RDW group(RDW＜13.35%)(24.42% vs 12.10%, P＜0.05). The multivariate Logistic regression analysis showed that the high RDW levels may be associated with MACE in acute STEMI patients after PCI treatment during hospitalization(OR=3.7,5%CI:1.275～7.093,P＜0.05). Conclusion RDW may be an independent risk factor for MACE in STEMI patients after PCI during hospitalization.

Abstract:Aim To explore the correlation between monocyte to high density lipoprotein ratio (MHR) and type 2 diabetes mellitus (T2DM) with arteriosclerosis obliterans (ASO) of lower extremity. Methods 340 T2DM patients admitted to our hospital from February 2017 to January 2019 were selected as research objects. According to the quartile of MHR, the patients were divided into four groups:group A (n＝85):MHR＜0.61×10⁹; group B (n＝85):MHR (0.61-0.90)×10⁹; group C (n＝85):MHR (0.91-1.17)×10⁹; group D (n＝85):MHR＞1.17×10⁹. The baseline data of patients were analyzed by single factor analysis, and Logistic regression analysis was carried out for the single factor with statistical significance, in order to analyze the correlation between MHR and ASO. The independent risk factors of ASO were discussed and the prediction model was established. ROC curve was used to evaluate the diagnostic efficiency of MHR to ASO. Results The incidence of ASO in group A, group B, group C and group D were 21.18%, 24.70%, 47.06% and 56.47% respectively. There was significant difference in the incidence of ASO among the four groups (P＜0.001). The differences of body mass index, MHR, course of disease, monocyte, fasting blood glucose, glycosylated hemoglobin A1 (HbA1c), serum creatinine, blood urea nitrogen, ankle brachial index (ABI), homocysteine (Hcy), serum uric acid (SUA), fasting insulin, apolipoprotein A1, apolipoprotein B, homeostasis model assessment index of insulin resistance (HOMA-IR), triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol (LDLC) were statistically significant among the four groups (P＜0.05). Logistic regression analysis showed that MHR, Hcy, HOMA-IR, LDLC, HbA1c and SUA were independent risk factors for ASO (P＜0.05). Pearson correlation analysis showed that there was a negative correlation between MHR and ABI (r＝－0.742, P＜0.001). ROC curve showed that the cut-off value of MHR for ASO diagnosis was 0.91×10⁹, the sensitivity was 79.53%, the specificity was 81.22%, and the area under curve was 0.815. Conclusion MHR is an independent risk factor for the occurrence of ASO in T2DM patients, which has a positive correlation with ASO, and has a certain value for the prediction and evaluation of ASO.

Abstract:Aim To study the relationship between the level of γ-glutamyltransferase(GGT) and the severity of coronary artery lesions and prognosis in patients with acute ST-segment elevation myocardial infarction(STEMI). Methods 282 cases of patients with STEMI underwent PCI were selected as the observation subjects. According to the fasting serum GGT level in the morning after admission, the patients were divided into normal group (n=197) and high-level group (n=85). The coronary artery disease, mortality and the incidence of major adverse cardiac events were analyzed and compared between the two groups. Results The Gensini score in the high level group was significantly higher than that in the normal group (P<0.05), and the GGT level was positively correlated with the Gensini score (r=0.598, P<0.05). Within one year of follow-up, 19 patients died in the high GGT group and 20 patients died in the normal group, with a total mortality rate of 13.83%. The mortality rate of 1 week, 1 month, 6 months and 1 year in the high level group was significantly higher than that in the normal group (P<0.05), the survival curve analysis showed that the 1 year mortality rate of STEMI patients in the high level group was significantly higher than that in the normal group. Cox regression analysis showed that KILLIP cardiac function grade (OR=2.9,5%CI 1.024~4.508), GGT (OR=2.8,5%CI 1.289~4.501) and age (OR=1.3,5%CI 1.032~1.095) were independent risk factors for prognosis in patients with STEMI; the incidence of major cardiovascular events (MACE) in patients with high level STEMI at 1 week, 1 month, 6 months and 1 year were significantly higher than those in normal group(P<0.05). Conclusion Serum GGT level is correlated with the degree of coronary artery disease and short-term and long-term prognosis in patients with STEMI, and high GGT level is an independent risk factor to evaluate the prognosis of STEMI patients.

Abstract:Aim To investigate the electroencephalographic characteristics of elderly post-stroke depression(PSD) and affecting factors of depression. Methods 500 cases of elderly stroke patients were selected and divided into PSD group (n=200, including mild group of 61cases, mid group of 85cases and severe group of 54 cases) and non-PSD group (n=300)according to the presence or absence of PSD. The EEG examination was performed onset within 7 d, and EEG amplitude, frequency, α, β, δ, θ wave distribution were observed, the affecting factors of stroke complicated depression in the elderly were analyzed by univariate and multivariate stepwise Logistic regression. Results The rate of EEG abnormality in PSD group (53.00%) was significantly higher than that in non-PSD group (43.67%), and the rate of low-amplitude δ wave (68.00%) was significantly higher than that in non-PSD group (54.00%, P<0.05). The rate of EEG abnormality in severe group (61.11%)was significantly higher than mild group of 32.79%(P<0.05). Univariate analysis showed that the rate of depression in elderly stroke patients with education, hypertension, depression, family relationship, lesion location, eeg characteristics were affecting factors of PSD. Multiple stepwise Logistic regression analysis showed that high educational level, history of hypertension, history of depression, family disagreement, basal ganglia lesion, low amplitude wave and EEG abnormality were independent risk factors for elderly PSD (P<0.05). Conclusions EEG of the elderly PSD shows mainly low amplitude δ wave. Education, hypertension, depression, family relationship, basal ganglia, low amplitude δ wave are closely related to PSD.

Abstract:The incidence of stroke in China has increased year by year, and carotid stenosis is one of the main causes of stroke. With the development of atherosclerotic inflammatory mechanisms, cytokines closely related to chronic inflammatory response are increasingly important in the study of carotid plaque pathogenesis. For carotid stenosis, it is important to fully understand the various cytokines involved in the pathogenesis of atherosclerosis. This article reviews the new understanding and research direction of several common cytokines in the process of carotid artery plaque lesions.

Abstract:Fibroblast growth factor-21(FGF-21) is a major regulator of glycolipid metabolism, which has great results in the improvement of diabetes, but there are many differences in the research on the beneficial effects of many cardiovascular diseases. This paper introduces the role of FGF-21 in the development of coronary heart disease, arrhythmia and heart failure, and provides a new direction for the study of FGF-21 in cardiovascular diseases.

Abstract:Human intestinal microorganisms are the collective name of all microorganisms in human digestive system. More and more studies have shown that changes in the composition and diversity of intestinal microorganisms are closely related to cardiovascular diseases. This article will discuss the correlation between intestinal microorganisms and heart failure, including the role of their metabolites (short-chain fatty acids, bile acids, trimethylamine and trimethylamine oxide) in the pathogenesis of heart failure, and explore how to precisely intervene intestinal microflora in order to provide new ideas for the treatment of heart failure patients.

Abstract:Cardiovascular disease (CVD) is a serious threat to human health. It is an urgent problem for clinicians to early detect and prevent the occurrence of cardiovascular events. Atherogenic index of plasma (AIP) is an independent predictor of CVD proposed in recent years. It is derived from the logarithm conversion of the ratio of triglyceride (TG) to high density lipoprotein cholesterol (HDLC), i.e., log[TG/HDLC]. Compared with the previous single index, AIP can more comprehensively reflect the level of lipid metabolism, which is of great significance for clinical diagnosis and treatment monitoring of diseases. This article reviews the application of AIP in CVD.