Abstract:Endothelial dysfunction, a common feature of various cardiovascular diseases, is closely associated with the overexpression of reactive oxygen species (ROS)/reactive nitrogen species (RNS). The reaction between superoxide anion and nitric oxide (NO) can generate peroxynitrite with stronger oxidation ability, which can deplete NO by oxidizing various proteins, leading to endothelial contraction and relaxation dysfunction, and playing an important role in various cardiovascular diseases. This article reviews the pathways through which nitrosylation modified proteins are produced and the possible mechanisms by which they promote endothelial dysfunction in cardiovascular disease. It discusses the relationship between ROS/RNS mediated nitrosylation modification and endothelial dysfunction, which together promote the progression of cardiovascular disease. The article also discusses the application of therapeutic strategies such as clearing peroxynitrite, inhibiting ROS production pathways, and directly enhancing endothelial cell function in cardiovascular diseases related to endothelial dysfunction, which can provide reference for further research on the role of protein nitration modification as a post-translational intervention target in cardiovascular diseases.

Abstract:Cerebral small vessel disease (CSVD) refers to a series of clinical imaging pathological syndromes caused by various etiologies affecting cerebral small vessels, which have the characteristics of insidious onset, high incidence and easy recurrence. Insulin resistance (IR) is a decrease in the bodys sensitivity to insulin. In recent years, more and more studies have confirmed that IR is associated with the occurrence and development of imaging features of CSVD, but the mechanism is still unclear. This article reviews the relationship between IR and cerebral small vessel disease and its possible mechanism, in order to provide reference for the prevention and treatment of cerebral small vessel disease.

Abstract:Aim To investigate the effect of transfection of recombinant adenovirus vector carrying angiotensin converting enzyme 2 (ACE2) gene (Ad-ACE2) on protecting endothelium, improving insulin resistance and inhibiting liver fibrosis in apolipoprotein E knock-out (ApoE-/-) mice fed with high-fat diet. Methods ApoE-/- mice were fed with high-fat and high-energy food to simulate metabolic syndrome. 30 ApoE-/- mice were randomly divided into control group (Con group), adenovirus empty vector group (EGFP group) and ACE2 gene therapy group (ACE2 group), with 10 mice in each group, and each group was given a high-fat diet. The 3 groups were injected respectively with normal saline, Ad-EGFP and Ad-ACE2 by intravenous injection of the tail vein. At the end of 12 weeks, glucose tolerance test and insulin tolerance test were carried out. After the mice anaesthesia, blood was extracted from heart tip and blood lipid level was measured. Liver tissue was taken with HE staining and oil red O staining. Immunohistochemical staining was used to observe the expressions of ACE2, collagen-Ⅰ (COL-Ⅰ), collagen-Ⅲ (COL-Ⅲ) and interleukin-6 (IL-6) in liver tissue. Results In ACE2 group, Ad-ACE2 transfection significantly increased the expression of ACE2 in ApoE-/- mice liver (P＜0.05). The endothelium-dependent function in ACE2 group was significantly better than that in Con group and EGFP group (P＜0.05), and insulin sensitivity was stronger than that in Con group and EGFP group (P＜0.05), but the level of blood lipid did not change significantly. The COL-Ⅰ, COL-Ⅲ and IL-6 expressions of liver tissue in ACE2 group were lower than those in Con group and EGFP group (P＜0.05). Conclusion ACE2 overexpression can protect the endothelium, improve insulin resistance, inhibit liver fibrosis and thus protect liver function.

Abstract:Aim To investigated the role and mechanism of macrophage in endothelial dysfunction and cardiac hypertrophy in AngⅡ-induced hypertensive mice. Methods C57BL/6 mice were randomly divided into four groups:normal+PBS group, normal+clodronate liposome (CL) group, Ang Ⅱ+PBS group, Ang Ⅱ+CL group. PBS or CL was injected via tail vein,and Ang Ⅱ was delivered by implantation of osmotic mini-pump. The systolic blood pressure (SBP) was measured by tail-cuff method, SBP was measured at 3 time points:at baseline, 7 days and 14 days after AngⅡ infusion. HE staining was used to measure myocardial hypertrophy, endothelium dependent relaxation to acetylcholine in aortic rings was determined by organ chamber bath, the protein expression of p-eNOS, p-ERK1/2 , TNF-α, IL-1β, TGF-β1, fibronectin was determined by Western blot. Results Compared with the normal+PBS mice, AngⅡ+PBS significantly increased systolic blood pressure (44%,P<0.05), macrophage infiltration in myocardial tissue (54%, P<0.05), heart weight (29%, P<0.05) as well as single myocardial cell area (48%, P<0.05), impaired acetylcholine-induced endothelium dependent relaxation (Emax-35%, P<0.05). The treatment with CL significantly reduced SBP (-25.28%, P<0.05), the area of single myocardial cell (-38.83%, P<0.05), and improve acetylcholine-induced endothelium dependent relaxation (Emax 12.63%, P<0.05) in AngⅡ hypertensive mice. CL treatment also restored the expression of p-eNOS, p-ERK1/2, TNF-α, IL-1β, TGF-β1, fibronectin induced by AngⅡ (P<0.05). Conclusions The results demonstrate that CL protects against AngⅡ-induced endothelial dysfunction and myocardial damage and remodeling, the underlying mechanisms may involve reduction in myocardial macrophage infiltration and macrophage-derived cytokines.

Abstract:G protein-coupled receptor 5 (TGR5) is recently discovered to be a new membrane receptor that can regulate inflammation and metabolism. TGR5 activation can inhibit foam cell formation and atherosclerotic plaque rupture by reducing inflammation reaction, promote NO, H2S and other endogenous gas signal molecules to improve vascular endothelial dysfunction. In addition, it also can reduce atherosclerosis risk factors such as obesity and diabetes. Therefore, TGR5 may be an important target for prevention and treatment of atherosclerosis.

Abstract:Inflammation mediated endothelial dysfunction plays an important role in the occurrence and development of obesity-induced cardiovascular disease. Omentin is a kind of anti-inflammatory adipokines, and there is a close relationship between obesity endothelial function. Regular exercise can produce anti-inflammatory effect, improve endothelial function in obese subjects and thereby reduce the risk of cardiovascular disease, through enhancing the expression and secretion of omentin in obesity. This paper is a review of recent research status of this field. It may provide a theoretical thinking for the further research of biological mechanisms of the regular exercise to improve the obesity-related vascular endothelial function.

Abstract:Endothelial microparticles （EMP） are particles with a diameter ranged from 0.1 to 1 μm released by the apoptosis or death of activated of endothelial cells.The current studies have proved that EMP is a key marker of endothelial dysfunction.Early improvement of the function integrity of the endothelial cells is a key approach for the prevention and treatment of endothelial dysfunction.This study reviewed the related literatures on EMP as a treatment target.

Abstract:Aim To explore whether the use of peripheral arterial tonometry （PAT） in the evaluation of admission vascular endothelial function of acute myocardial infarction （AMI） patients can predict recurrence of major adverse cardiovascular events （MACE）. Methods For 116 consecutive patients clinically diagnosed with AMI received evaluation of vascular endothelial function using PAT technique within 72 hours of admission, reactive hyperemia index （RHI） was calculated. By the cut point of normal RHI （1.67） patients were divided into the normal endothelial function group （RHI≥1.67） and the endothelial dysfunction group （RHI＜1.67）, follow-up of MACE was conducted in both groups during hospitalization （median value 8.0 days） and after discharge from hospital （243.8±68.3 days）. MACE included cardiac death, recurrent acute myocardial infarction, recurrent unstable angina during hospitalization, ischemic stroke, elective percutaneous coronary intervention （PCI） or coronary artery bypass grafting （CABG）, and hospitalization due to cardiovascular causes. Result There was no significant difference in recurrence of MACE between PAT-determined endothelial dysfunction group （RHI＜1.67） and normal endothelial function group （RHI≥1.67） both during hospitalization and after discharge from hospital （P＝0.098 and 0.104, respectively）. Conclusion PAT cannot predict recurrence of major adverse cardiovascular events in AMI patients both during hospitalization and after discharge from hospital.

Abstract:AimTo investigate the effects of glycine on endothelial function in rats with a high-fructose diet induced hypertension and the mechanisms of glycine on lowering hypertension.MethodsModel group rats were fed with 8% fructose water, and glycine intervention group rats were fed with water containing 8% fructose and 1% glycine.The body weight and systolic blood pressure were measured monthly, and the animals were killed in 4 th month and 8 th month respectively.The levels of plasma glucose, insulin, endotoxin, TNF-α, IL-6, NO and endothelin-1 (ET-1) were detected, and HOMA-IR was calculated.The expression of endothelial nitric oxide synthase (eNOS) was determined by immunohistochemistry, and the expression of endothelin A receptor (ETA-R) mRNA was analyzed by RT-PCR.ResultsThe body weight and systolic blood pressure were increased in model group after 3 months.The levels of plasma glucose, insulin, HOMA-IR, endotoxin, pro-inflammatory cytokines, ET-1 and the expression of ETA-R mRNA were increased in model group, but the levels of plasma NO and the expression of eNOS were decreased in 4 th and 8 th month.However, there was no significance of the parameters at different stages.Glycine significantly reduced the weight gain at 4 th month and 6 th month, and reduced the elevated systolic blood pressure in 4 th month to 6 th month, and significantly decreased the levels of plasma insulin, HOMA-IR, endotoxin, pro-inflammatory cytokine, ET-1 and the expression of ETA-R mRNA in 4 th and 8 th month, and significantly increased the levels of plasma NO and the expression of eNOS in 4 th month.ConclusionsGlycine can ameliorate early hypertension induced by a high-fructose diet, which may be related

Abstract:Endothelial microparticles are submicron membrane vesicles shed from plasma membranes in response to endothelial cell activation or injury and play a major biological role in adhesion, inflammation and angiogenesis.Recent studies indicate that endothelial microparticles are involved in the development of coronary heart disease for their close association with oxidative stress, endothelial dysfunction and vulnerable plaque rupture.Thus, elucidating their role and their mechanisms of formation will bring new insights into the understanding of coronary heart disease.