Abstract:High density lipoprotein (HDL) is protective against atherosclerosis through multiple functions, including mediating reverse cholesterol transport, anti-oxidation, anti-inflammation, and endothelial protection. However, in the state of inflammation and metabolic diseases, due to alteration, oxidation or modification of HDL composition, HDL particles can be transformed into proatherosclerotic “dysfunctional” HDL, which is associated with an increased incidence of cardiovascular events. This paper reviews the composition and functional characteristics of dysfunctional HDL in order to provide new diagnostic and therapeutic approaches for atherosclerotic cardiovascular disease.

Abstract:Aim To investigate the correlation between serum homocysteine (Hcy) level and high density lipoprotein (HDL) subclasses in patients with H-type hypertension, and to study the function of HDL subclasses on the anti-inflammatory capacity of endothelial cells. Methods 76 patients with isolated hypertension, 85 patients with H-type hypertension and 133 healthy adults were included in our study. The concentration of fasting blood glucose (FBG), serum creatine(SCr), uric acid (UA), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), HDL2, HDL3 and Hcy were measured for each participants. Furthermore, HDL subclasses were isolated and purified from plasma of 6 participants for each group by fast protein liquid chromatography (FPLC). Large HDL (L-HDL) anti-inflammatory capacity was determined as its ability to suppress tumor necrosis factor alpha (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical vein endothelium (HUVEC) in vitro. Results There were no significant differences of FBG, UA, TC, LDLC level between health control, isolated hypertension and H-type hypertension(P＞0.05). Compared with health control and isolated hypertension, patients with H-type hypertension had significantly lower level of HDL2 and HDLC and higher level of HDL3(P＜0.001). Correlation analysis indicated that plasma Hcy level was negatively related with HDLC(r＝－0.532,P＜0.01) and HDL2 level (r＝－0.626, P＜0.01). There was no significant relationship between plasma Hcy level and HDL3 (r＝0.10,P＝0.083). The L-HDL from health controls and patients with isolated hypertension significantly decreased TNF-α-induced VCAM-1 expression in HUVEC (P＜0.05). However, the L-HDL from patients with H-type hypertension indicated no effect on decreasing TNF-α-induced VCAM-1 expression in HUVEC (P＞0.05). Conclusion Patients with H-type hypertension had abnormal HDL subclasses distribution and decreased function of L-HDL on anti-inflammatory capacity of HUVEC.

Abstract:Aim To study the correlation between the antioxidantion of plasma high density lipoprotein (HDL) and circulating microRNA (miRNA). Methods Scavenger receptor group B type Ⅰ deficient (SR-BⅠ－/－) mice as dysfunctional HDL model mice were used to explore the changes of specific miRNA spectrum. From September 2020 to May 1,0 patients with coronary artery disease (CAD) were enrolled in the Department of Cardiology, Zhongnan Hospital of Wuhan University, non-CAD patients in the same period as control group, both groups with HDL cholesterol (HDLC) higher than 1.04 mmol/L. Results Compared with wild-type mice, the plasma miR-135a in SR-BⅠ－/－ mice decreased significantly. Plasma paraoxonase 1 (PON-1) activity decreased in CAD patients, PON-1 activity in control group was positively correlated with HDLC level, but not in CAD group. The plasma miR-135a level in CAD patients also decreased, and was positively correlated with PON-1 activity. In CAD group, the level of plasma miR-17 decreased significantly, and the levels of miR-223 and miR-760 increased significantly, but there was no correlation with HDLC level or plasma PON-1 activity. Conclusion The level of plasma miR-135a decreased significantly in CAD patients with high HDLC, and was positively correlated with PON-1 activity, which may be related to the antioxidant function of HDL.

Abstract:Aim To investigate the effect of apolipoprotein O knockout mice promoting obesity and metabolic disorders challenged by high fat diet (HFD). Methods Breeding the ApoO heterozygous mice will get the homozygous mice offspring. PCR reaction was used to detect the gene genotype after extracting the mice tissue DNA. mRNA and protein expression of ApoO were determined by quantitative real-time PCR(qRT-PCR) and Western blot assay, respectively. After feeding with high-fat diet, the metabolic phenotypes in mice were observed by somatotype, food intake, lipidomic study in liver. Results The homozygous mice offspring were obtained. It was found that homozygous mice had obesity and more severe hepatic steatosis after HFD challenging. Lipidomics of the liver revealed obvious accumulation of triglyceride and significant changes of phospholipid components. Conclusion The deletion of ApoO may promote obesity and metabolic disorders induced by high-fat diet, which could provide a new target for the prevention and treatment of metabolic syndrome and cardiovascular diseases.

Abstract:Aim To observe whether mechanical stretch stress (SS) induces the proliferation and migration of mouse vascular smooth muscle cells (VSMC) through PKCδ activation, and to further explore the effect and mechanism of berberine (BBR) on the proliferation and migration of VSMC. Methods Mouse VSMC in vitro were divided into six groups:negative control group (NC), berberine group (BBR), PKCδ inhibitor Sotrastaurin group (Sotras), SS group, SS+BBR group and SS+Sotras group. The cultured VSMC in each group,which were pretreated with BBR or Sotrastaurin or ddH₂O for 1h, followed by SS (10% tensile strength) for different time or no treatment for control, were collected for the detection of PKCδ phosphorylation, proliferation and migration by Western blot, immunofluorescence and scratch assay respectively. Results Immunofluorescence and cell scratch test results showed that compared with NC group, SS stimulation significantly increased Ki67 positive level in VSMC by 469%(P＜0.05, n＝3), and reduced scratch width by 54.9%(P＜0.05, n＝3),while BBR and Sotrastaurin could significantly inhibit the changes caused by SS, Ki67 positive level decreased by 66.9% and 80.2%(P＜0.05, n＝3), and scratch width increased by 79.4% and 120.1%(P＜0.05, n＝3)compared with SS group, respectively. Meanwhile, Western blot results showed that SS stimulation induced a time-dependent increase in PKCδ phosphorylation compared with NC group, with the most significant increase of 97.5%(P＜0.05,n＝3) at 30 min, which also inhibited by berberine in a concentration-dependent manner, and the effect was the most significant at 200 μmol/L, with a decrease of about 37.6% (P＜0.05, n＝3). Conclusion Berberine inhibits SS-induced vascular smooth muscle cell proliferation and migration by inhibiting PKCδ phosphorylation.

Abstract:Aim To confirm the protective effect of cordycepsmilitaris polysaccharide (CMPS) on nonalcoholic fatty liver disease (NAFLD) in ApoE－/－ mice fed with high-fat diet and explore the underlying mechanism. Methods32 ApoE－/－ mice were randomly divided into ApoE－/－group and CMPS (5,0, 100 μg/g) treatment groups, all of which were fed with high-fat diet. The treatment groups were simultaneously fed with respective doses of CMPS. Another 8 C57BL/6 mice were fed with chow diet as control group (WT group). After 12-weeks experimental period, the mice were sacrificed. The liver index of mice was calculated and the histological changes of liver were observed by HE staining. The serum triglyceride (TG) concentration, liver TG concentration, superoxide dismutase (SOD) activity and lipid peroxide (LPO) content were detected according to the kit instructions. The levels of peroxisome proliferator-activated receptor α (PPARα) and acyl-CoA oxidase 1 (ACOX1) were analyzed by quantitative PCR and Western blot. Results Compared with ApoE－/－ group, CMPS treatment significantly reduced liver weight and liver index, alleviated hepatic steatosis induced by high-fat diet, and reversed the increasement of TG levels in liver and serum. Meanwhile, the mRNA and protein expressions of PPARα and ACOX1 were up-regulated in liver of CMPS treatment groups compared with those of ApoE－/－group. In addition, CMPS treatment enhanced the activity of SOD and lowered the content of LPO in the liver of ApoE－/－ mice. Conclusion CMPS can effectively improve NAFLD induced by high-fat diet in ApoE－/－ mice, which may be related to its promotion of fatty acid oxidation and inhibition of oxidative stress.

Abstract:Aim To study the expression and biological significance of microRNA-499 (miR-499) and high mobility group protein 1 (HMGB1) in carotid atherosclerotic plaque. Methods Patients with carotid atherosclerosis diagnosed in Sanmenxia Central Hospital of Henan Province from January 2018 to December 2020 were enrolled in the carotid atherosclerosis group, and healthy people were enrolled in the control group. The expression level of miR-499 in peripheral blood and the content of HMGB1 in serum were detected. Apolipoprotein E (ApoE) knockout mice were divided into groups and fed with high cholesterol diet to establish carotid atherosclerotic plaque model. miR-NC, miR-499, NC lentivirus (lenti-NC) and HMGB1 lentivirus (lenti-HMGB1) were given by tail vein injection. Then the pathological changes, the expression levels of miR-499 and HMGB1 in carotid atherosclerotic plaque were determined. Human umbilical vein endothelial cells (HUVEC) were cultured and double luciferase reporter gene was used to verify the targeted binding of miR-499 and HMGB1. Results The expression level of miR-499 in peripheral blood of carotid atherosclerosis group was lower than that of control group, and the content of HMGB1 in serum was higher than that of control group, and the expression level of miR-499 was negatively correlated with the content of HMGB1 in serum (P＜0.05). The expression level of miR-499 in carotid atherosclerotic plaque of model group was lower than that of control group, and the expression level of HMGB1 was higher than that of control group; the pathological changes of carotid atherosclerotic plaque in miR-499+model group were better than those in miR-NC+model group, the expression level of miR-499 in carotid atherosclerotic plaque was higher than that of miR-NC+model group, the expression level of HMGB1 was lower than that of miR-NC+model group. The pathological changes of carotid atherosclerotic plaque in lenti-HMGB1+miR-499+model group were more severe than those in lenti-NC+miR-499+model group, and the expression level of HMGB1 was higher than that in lenti-NC+miR-499+model group. The fluorescence value of wild-type HMGB1 reporter gene in miR-499 group was significantly lower than that in miR-NC group (P＜0.05). Conclusion miR-499 targeting HMGB1 is involved in the formation of carotid atherosclerotic plaque.

Abstract:Aim To study correlation between left ventricular hypertrophy (LVH) and index of blood pressure variability(BPV) in patients with hypertension complicated with diabetes mellitus. Methods 120 hypertension patients combined with diabetes mellitus were included, and divided into LVH group and non-LVH group according to their clinical confirmed information and electrocardiographic data. BPV-related indices were compared between the two groups, Logistic regression was used to analyze the risk associated with LVH in patients. Pearson correlation analysis was used to analyze the correlation between left ventricular mass index (LVMI) and BPV. Results In patients with hypertension and diabetes, daytime systolic blood pressure variability coefficient (dSBPCV), daytime diastolic blood pressure variability coefficient (dDBPCV), 24 h systolic blood pressure variaility coefficient (24hSBPCV), and 24 h diastolic blood pressure variability coefficient (24hDBPCV) in LVH group were significantly higher than those in non-LVH group (P＜0.05). Logistic regression analysis showed that the increase of dSBPCV, dDBPCV, 24hDBPCV and 24hSBPCV were related risk factors for LVH in hypertensive patients with diabetes mellitus (OR＞1, P＜0.05). Pearson correlation analysis showed that LVMI was positively correlated with 24hSBPCV, 24hDBPCV, dSBPCV and dDBPCV (r＝0.5,0.2,0.387 and 0.441, P＜0.05). Conclusions BPV in hypertensive patients with diabetes mellitus has a certain effect on left ventricular hypertrophy. BPV can be used as a predictor of target organ damage in hypertensive patients with diabetes mellitus. BPV control has a certain clinical value for early prevention and treatment of left ventricular hypertrophy.

Abstract:Aim To explore the diagnostic value of peripheral blood monocyte to high density lipoprotein cholesterol ratio (MHR) in lower extremity arterial stenosis. Methods 311 consecutive cases treated in the Eighth Affiliated Hospital of Sun Yat-sen University from August 2018 to August 2020 were selected. According to the degree of lower extremity arterial stenosis, the patients were divided into four groups:(1)control group (n＝65):lower extremity artery was normal; (2)mild lesion group (n＝77):30%≤lower extremity arterial stenosis＜50%; (3)moderate lesion group (n＝60):50%≤lower extremity arterial stenosis ≤ 75%; (4)severe lesion group (n＝109):lower extremity arterial stenosis＞75% or occlusion. MHR was calculated. The clinical data and laboratory results of the four groups were collected and compared. The influencing factors of lower extremity arterial stenosis and the diagnostic value of MHR in lower extremity arterial stenosis were analyzed. Results The differences in age, MHR, high-sensitivity C-reactive protein, hemoglobin, high-density lipoprotein cholesterol, serum creatinine (SCr), blood uric acid, blood homocysteine, history of hypertension, and history of diabetes were statistically significant among the four groups (P＜0.05). Multivariate Logistic regression analysis showed that advanced age, high MHR, high SCr and history of diabetes were risk factors for patients with lower extremity arterial stenosis (P＜0.05). Based on the predicted probability obtained from the multivariate Logistic regression model, the ROC curve was drawn, and the area under the curve was 0.953; When the predicted probability is 0.86, the sensitivity and specificity for the diagnosis of lower extremity arterial stenosis were 85.8% and 92.3%.Conclusions High MHR is a risk factor for lower extremity arterial stenosis. The multivariate Logistic regression model established in this article has a high diagnostic value for lower extremity arterial stenosis.

Abstract:Aim To analyze the relationship between the levels of serum human cartilage glycoprotein 39 (YKL-40), soluble tumor necrosis factor receptor 1 (sTNFR1) and cardiac function and prognosis in patients with acute myocardial infarction (AMI). Methods 77 patients with AMI treated in the First Affiliated Hospital of Hebei North University from March 2016 to October 2018 were selected as the research object (AMI group), and 77 cases undergoing health physical examination in the hospital in the same period were selected as the control group. AMI patients were followed up after discharge, and the prognosis was recorded; The follow-up time was 24 months. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and left ventricular posterior wall thickness (LVPWT) were measured by echocardiography; Serum YKL-40 and sTNFR1 levels were determined by enzyme-linked immunosorbent assay; Pearson method was used to analyze the correlation between serum YKL-40, sTNFR1 levels and cardiac function parameters in AMI patients; The relationship between serum YKL-40, sTNFR1 levels and poor prognosis was analyzed in AMI patients; The risk factors affecting the poor prognosis of AMI patients were analyzed by COX regression. Results Compared with the control group, the levels of serum YKL-40, sTNFR1, LVEDD and LVPWT were significantly increased, and LVEF was significantly decreased in AMI group (P＜0.05). With the increase of cardiac function grade in AMI patients, the levels of serum YKL-40 and sTNFR1 increased gradually (P＜0.05). The levels of serum YKL-40 and sTNFR1 were negatively correlated with LVEF and positively correlated with LVEDD and LVPWT in AMI patients (P＜0.05).In AMI patients, the incidences of poor prognosis in high-level YKL-40 group and high-level sTNFR1 group were higher than those in low-level group (P＜0.05). Multivariate COX analysis showed that the type and location of myocardial infarction and the levels of serum YKL-40 and sTNFR1 were risk factors for poor prognosis in AMI patients (P＜0.05). Conclusion The levels of serum YKL-40 and sTNFR1 are related to cardiac function and poor prognosis in AMI patients, which may be potential biomarkers to evaluate the prognosis of AMI patients.

Abstract:Aim To investigate the relationship between estimated glomerular filtration rate (EGFR), serum uric acid (SUA), fibrinogen (FIB) and cerebral hemorrhage transformation and clinical outcome after thrombolysis in ischemic stroke. Methods 158 patients with ischemic stroke treated with recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis were selected, including 121 cases without cerebral hemorrhage transformation and 37 cases with cerebral hemorrhage transformation. Logistic regression equation was used to analyze the influencing factors of cerebral hemorrhage transformation after intravenous thrombolysis with rt-PA. The levels of eGFR, SUA and FIB were compared in patients with different early neurological function. The predictive values of eGFR, SUA and FIB for early neurological deterioration (END) were evaluated. The cumulative survival rates of patients with different levels of eGFR, SUA and FIB were compared. Results After intravenous thrombolysis with rt-PA for 2 h and 24 h, the levels of eGFR, SUA and FIB in patients with cerebral hemorrhage transformation were lower than those without cerebral hemorrhage transformation (P＜0.05). Logistic regression analysis showed that age, baseline NIHSS score, baseline diastolic blood pressure, large-area cerebral infarction, levels of eGFR, SUA and FIB at 2 h and 24 h after thrombolysis were the influencing factors of cerebral hemorrhage transformation after rt-PA intravenous thrombolysis (P＜0.05). eGFR, SUA and FIB in END patients were lower than those in non-END patients at 2 h and 24 h after thrombolysis (P＜0.05). ROC curve analysis showed that the area under curve for the joint predicting END by 24 h eGFR, 24 h SUA and 24 h FIB was 0.809, which was greater than any single index, and its sensitivity and specificity were 80.95% and 74.14% respectively. The results of survival analysis showed that the cumulative survival rate of high-level eGFR, SUA and FIB group was higher than that of low-level group 24 h after thrombolysis (P＜0.05). Conclusion eGFR, SUA, FIB are closely related to the prognosis of ischemic stroke. Monitoring the above indicators is helpful for the diagnosis of cerebral hemorrhage transformation and END prediction.

Abstract:Atherosclerosis is a common cardiovascular disease with high mortality. Heparanase is an endogenous β-D-glucuronidase that can cleave the upper side chain of acetylproteoglycan sulfate in the outer membrane of the cell. And its non-enzymatic activity also plays a role in many normal physiological activities or pathological diseases. Studies have shown that heparanase is closely related to the formation and progression of atherosclerosis. This paper reviews the effects of heparanase on endothelial injury, coagulation, inflammatory factors and lipid accumulation, and expounds its role and mechanism in the occurrence and development of atherosclerosis.

Abstract:Cardiovascular disease is the leading cause of death in the world. The economic cost of treatment and diagnosis is very high. In the past two decades, the diagnosis, treatment and evaluation of patients with coronary heart disease have undergone various changes. Positron emission tomography is a powerful and multi-functional noninvasive imaging examination, especially by quantifying the myocardial blood flow and coronary flow reserve, it can better describe the characteristics of coronary artery disease, play an important role in the early diagnosis, classification and treatment of coronary microvascular disease and ischemic cardiomyopathy.

Abstract:Cardiovascular disease (CVD) is a serious threat to human health. Atherosclerosis (As), as an important pathological basis of CVD, is a chronic immune inflammatory disease caused by the deposition of oxidized lipid in the vascular wall. Various immune inflammatory cells play a key role in the occurrence and development of As, so it is very important to explore the mechanism of immune cells in the pathological changes to study the treatment strategy of CVD.In this paper, the functions of neutrophils, monocytes, lymphocytes, dendritic cells and mast cells in As are reviewed.

Abstract:Sestrin 2 is a highly conserved stress-induced metabolic protein, which has the effects of antioxidation and improving the level of autophagy. It protects cells against various harmful stimuli, including genotoxicity, oxidative stress, endoplasmic reticulum stress and hypoxia. Sestrin 2 plays an important role in the occurrence and development of glycolipid metabolism related diseases by regulating the level of oxidative stress and autophagy, and is expected to become a new target for the diagnosis and treatment of glycolipid metabolism related diseases. Here, this article reviews the relationship between sestrin 2 and glycolipid metabolism related diseases.