摘要：
Caveolin-1 is considered an important pathophysiological factor in atherosclerosis development. Previous studies indicate that caveolin-1 exhibits a pathogenic capacity in atherosclerosis via the regulation of membrane trafficking, cholesterol metabolism and cellular signal transduction. Accumulating evidence shows that autophagy activation influences the progression and development of atherosclerosis in multiple ways, including cholesterol metabolism, inflammatory responses and lipid transcytosis. However, how caveolin-1 is involved in autophagy activation in atherosclerosis remains unclear, and the precise mechanisms of caveolin-1 on autophagic flux in atherosclerosis need to be further investigated. Clarifying the roles and mechanisms of caveolin-1 in the regulation of autophagy activation is of great importance, contributing to the ability to manipulate caveolin-1 as a novel therapeutic approach for atherosclerosis. In this review, we summarize the understanding of the molecular structure, biological roles and biochemical functions of caveolin-1 to date and discuss the roles and mechanisms of caveolin-1 in autophagy activation. The emphasis on the potential of caveolin-1 to be a novel therapeutic target in atherosclerosis and understanding its precise functions and exact mechanisms in autophagic flux will provide evidence for future experimental research and aid in the development of novel therapeutic strategies for atherosclerosis.
作者机构：
[洪陈亮; 王珍; 秦旭平] Lab of Vascular Biology, Institute of Pharmacy and Pharmacology, University of South China, Hunan, Hengyang, 421001, China;Dept of Clinical Pharmacy, the First People's Hospital of Huaihua, Hunan, Huaihua, 418000, China;[袁李佳龙] Lab of Vascular Biology, Institute of Pharmacy and Pharmacology, University of South China, Hunan, Hengyang, 421001, China, Dept of Clinical Pharmacy, the First People's Hospital of Huaihua, Hunan, Huaihua, 418000, China
通讯机构：
[Qin, X.-P.] L;Lab of Vascular Biology, Hunan, China
作者机构：
[Li, Jie; Tang, Hong-Xia; Qin, Xu-Ping] Univ South China, Peoples Hosp Chenzhou 1, Inst Pharm & Pharmacol, Chenzhou, Hunan, Peoples R China.;[Li, Jie] Southern Med Univ, Sch Pharm, Guangzhou, Guangdong, Peoples R China.;[Li, Jie] Univ South China, Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.
通讯机构：
[Li, Jie] U;Univ South China, Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.
关键词：
STAT3;VSMCs;CVDs;proliferation;pathway
摘要：
<jats:sec><jats:title>Objectives</jats:title><jats:p>Cardiovascular disease (CVD) remains the primary cause of morbidity and mortality worldwide. The abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of CVD. The functional and phenotypic changes in vascular cells are mediated by complex signaling cascades that initiate and control genetic reprogramming. Many studies have demonstrated that signal transducer and activator of transcription 3 (STAT3) regulates a diverse array of functions relevant to atherosclerosis.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this review, we summarize the studies on the STAT3-mediated proliferation of VSMCs and subsequent CVDs such as hypertension, atherosclerosis, stroke, coronary artery disease, and myocardial infarction. Furthermore, we describe the general background of STAT3, its structure, function and regulation as well as the STAT3 signaling pathway. Finally, we highlight some potential issues and propose some solutions to these issues. Results and conclusions: STAT3 activation promotes the proliferation of VSMCs by regulating the transcription of genes. Studying the mechanism of VSMC proliferation induced by the STAT3 pathway is valuable for finding therapeutic targets for CVD.</jats:p></jats:sec>
作者机构：
[李洁] The First People's Hospital of Chenzhou, Chenzhou, 423000, China;[秦旭平] Institute of Drug and Pharmacology, University of South China, Hengyang, 421001, China;[周楠] Medical College, Xi'an Jiaotong University, Xi'an, 710061, China;[林杰; 陈根] The First People's Hospital of Chenzhou, Chenzhou, 423000, China, Institute of Drug and Pharmacology, University of South China, Hengyang, 421001, China
通讯机构：
[Li, J.] T;The First People's Hospital of ChenzhouChina
关键词：
TLR4单克隆抗体;轻度氧化修饰低密度脂蛋白;炎症;肠系膜动脉;内皮依赖性舒张
摘要：
目的探讨预先使用TLR4单克隆抗体(TLR4mAb)对轻度氧化修饰低密度脂蛋白(mmLDL)诱发小鼠肠系膜动脉内皮依赖性舒张功能损伤的影响及作用机制。方法实验分为:空白对照组、mmLDL处理组、TLR4mAb干预组。采用ELISA方法测定血浆中白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α的浓度水平,微血管张力描记技术测定血管内皮依赖性舒张功能, Western blot技术和RT-PCR技术分别考察血管组织蛋白表达量和mRNA表达水平,透射电镜观察肠系膜动脉内皮细胞超显微结构。结果TLR4mAb剂量依赖性改善mmLDL损伤血管内皮依赖性舒张功能的损伤作用,显著上调KCa3.1-通道、KCa 2.3-通道蛋白表达和下调炎症因子TNF-α和IL-1β表达。TLR4mAb改善mmLDL损伤血管内皮细胞及内皮依赖性舒张功能,可能与其竞争性拮抗mmLDL激活TLR4信号转导通路及其下游的NF-κBp65和p-38MAPK通路有关。结论预先使用TLR4mAb可以减轻mmLDL所诱发的内皮细胞损伤和内皮依赖性舒张功能降低,以及抑制炎症因子的过度表达,调控TLR4通路及其下游的NF-κBp65和p-38MAPK通路可能是预防治疗心血管疾病的有效靶点。 <&wdkj&>OBJECTIVE To investigate the effect and mechanism of TLR4 monoclonal antibody (TLR4mAb) on mmLDL induced impairment of endothelium-dependent vasodilatation in mouse mesenteric artery. METHODS The experiment established three groups of normal saline group,mmLDL treatment group and TLR4mAb intervention group. The concentration of IL-1β and TNF-α in plasma was determined by enzyme-linked immunosorbent assay (ELISA) . Measurement of endothelium-dependent vasodilatation was achieved by microvascular tension mapping. Western blot and RT-PCR were used to investigate the expression level of protein and mRNA expressions in vascular tissues. In addition,ultra-structure of mesenteric artery endothelial cells was observed by transmission electron microscope. RESULTS TLR4mAb could improve the damage of mmLDL induced impairment of endothelium-dependent vasodilatation in a dose-dependent manner. Besides,TLR4mAb obviously up-regulated protein expressions in KCa 3.1-channel and KCa 2.3-channel,and down-regulated the expression of inflammatory factors TNF-α and IL-1β. Furthermore,the improvement of mmLDL impaired vascular endothelial cells and endothelium-dependent vasodilatation might be correlated with its competitive antagonism of mmLDL-activated TLR4 signal transduction pathway and its downstream NF-κBp65 and p-38 MAPK pathway. CONCLUSION Administration of TLR4mAb in advance can alleviate the impairment of endothelial cells and the decrease of endothelium-dependent vasodilatation induced by mmLDL,and inhibit the overexpression of inflammatory factors. Regulation of TLR4 pathway as well as its downstream NF-κBp65 and P-38 MAPK pathways may be effective targets for the prevention and treatment of cardiovascular diseases.
摘要：
Rutaecarpine attenuates hypertensive cardiac hypertrophy in the rats with abdominal artery constriction (AAC); however, its mechanism of action remains largely unknown. Our previous study indicated that NADPH oxidase 4 (Nox4) promotes angiotensin II (Ang II)-induced cardiac hypertrophy through the pathway between reactive oxygen species (ROS) and a disintegrin and metalloproteinase-17 (ADAM17) in primary cardiomyocytes. This research aimed to determine whether the Nox4-ROS-ADAM17 pathway is involved in the protective action of rutaecarpine against hypertensive cardiac hypertrophy. AAC-induced hypertensive rats were adopted to evaluate the role of rutaecarpine in hypertensive cardiac hypertrophy. Western blotting and real-time PCR were used to detect gene expression. Rutaecarpine inhibited hypertensive cardiac hypertrophy in AAC-induced hypertensive rats. These findings were confirmed by the results of in vitro experiments that rutaecarpine significantly inhibited Ang II-induced cardiac hypertrophy in primary cardiomyocytes. Likewise, rutaecarpine significantly suppressed the Nox4-ROS-ADAM17 pathway and over-activation of extracellular signal-regulated kinase (ERK) 1/2 pathway in the left ventricle of AAC-induced hypertensive rats and primary cardiomyocytes stimulated with Ang II. The inhibition of Nox4-ROS-ADAM17 pathway and over-activation of ERK1/2 might be associated with the beneficial role of rutaecarpine in hypertensive cardiac hypertrophy, thus providing additional evidence for preventing hypertensive cardiac hypertrophy with rutaecarpine.
期刊：
BioMed Research International,2018年2018:1547452 ISSN：2314-6133
通讯作者：
Qin, Xu-ping
作者机构：
[Zeng, Si-yu; Lu, Hui-qin] Guangdong Second Prov Gen Hosp, Inst Drug Clin Trial, Guangzhou 510317, Guangdong, Peoples R China.;[Luo, Jing-fei; Qin, Xu-ping; Quan, Hai-yan; Liu, Yu-huan] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Luo, Jing-fei; Qin, Xu-ping; Quan, Hai-yan; Liu, Yu-huan] Univ South China, Inst Pharm & Pharmacol, Lab Vasc Biol, Hengyang 421001, Hunan, Peoples R China.;[Xiao, Yun-bin] Univ South China, Acad Pediat, Changsha 410007, Hunan, Peoples R China.
通讯机构：
[Qin, Xu-ping] H;[Qin, Xu-ping] U;Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Lab Vasc Biol, Hengyang 421001, Hunan, Peoples R China.
摘要：
<jats:p><jats:italic>Objectives</jats:italic>. Protein arginine methyltransferase 2 (PRMT2) protects against vascular injury-induced intimal hyperplasia; however, little is known about the role of PRMT2 in angiotensin II (Ang II)-induced VSMCs proliferation and inflammation. This research aims to determine whether PRMT2 inhibits Ang II-induced proliferation and inflammation of vascular smooth muscle cells (VSMCs).<jats:italic> Materials and Methods</jats:italic>. PRMT2 overexpression was used to elucidate the role of PRMT2 in Ang II-induced VSMCs proliferation and inflammation. Western blotting and reverse transcriptional PCR were adopted to detect protein and mRNA expression severally. Cell viability was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and cell cycle distribution by flow cytometry.<jats:italic> Results</jats:italic>. Ang II significantly reduced mRNA and protein levels of PRMT2 in VSMCs in time-dependent and dose-dependent manner. Results of PRMT2 overexpression indicated that PRMT2 inhibited proliferation of VSMCs stimulated with 100 nmol/L Ang II for 24 hours. Furthermore, overexpression of PRMT2 reduced Ang II-induced production of proinflammatory cytokines such as interleukin 6 (IL-6) and interleukin 1<jats:italic>β</jats:italic> (IL-1<jats:italic>β</jats:italic>) in VSMCs.<jats:italic> Conclusions</jats:italic>. These findings suggest that PRMT2 alleviates Ang II-induced VSMCs proliferation and inflammation, providing a new mechanism about how Ang II mediated VSMCs proliferation and inflammation.</jats:p>
作者机构：
[张晓一] Dept of Pharmacy, Changzhi Medical College, Changzhi Shanxi, 046000, China;[秦旭平; 刘玉环; 杨丽; 郭峰; 阳芳; 王珍] Institute of Pharmacy and Pharmacology, University of South China, Hengyang Hunan, 421001, China
期刊：
Journal of the American College of Cardiology,2017年69(11):1881 ISSN：0735-1097
作者机构：
Hunan Childrens Hosp, Dept Cardiol, Changsha, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Xiao, Yunbin; Peng, Hongyan; Qin, Xuping; Chen, Zhi; Hong, Chenliang; Deng, Xicheng; Luo, Jinwen] Department of Cardiology, Hunan Children's Hospital, Changsha, People's Republic of China<&wdkj&>Institute of Pharmacy and Pharmacology, University of South China, Hengyang, People's Republic of China
会议名称：
66th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)
摘要：
Pulmonary arterial hypertension (PAH) is a rare yet fatal condition that is characterized by a continuous and notable elevation of pulmonary arterial pressure (PAP), resulting in right heart failure and death. Pulmonary arterial remodelling does not result from abnormal proliferation of pulmonary arterial vascular smooth muscle cells (PASMCs) but from pulmonary arterial endothelial cell (PAEC) dysfunction. However, the pathological mechanism of these two types of vascular cells in pulmonary artery remodelling is unclear. The Warburg effect describes aerobic glycolysis wherein cells commonly reprogram their energy metabolism to preferentially utilize glycolysis over oxidative phosphorylation for ATP production. Recent research has demonstrated that the Warburg effect plays a significant role in the development of PAH, which involves the abnormal proliferation of PASMCs and endothelial dysfunction. This review attempts to illustrate the functions of the Warburg effect in PAH, which may provide a new therapeutic target for PAH treatment. (C) 2016 Elsevier B.V. All rights reserved.
作者机构：
[Feng Guo; Hongyan Peng; Jingfei Luo; Haiyang Quan; Yanmei Liu; Jie Li; Zhisheng Jiang; Xuping Qin] Institute of Pharmacy & Pharmacology, Key Laboratory for Arteriosclerology of Hunan Province, University of South China
摘要：
Minimally modified low density lipoprotein (mmLDL) is a risk factor for cardiovascular diseases. However, no studies examining the effect of mmLDL on vascular smooth muscle receptors have been released. The current study investigated the effect of mmLDL on the mesenteric artery at adrenoceptor and the molecular mechanisms. Mice were divided into the normal saline (NS), mmLDL, and mmLDL + U0126 groups. In the mmLDL + U0126 group, the animals were subjected to an intravenous tail injection of mmLDL and an intraperitoneal injection of U0126. Vascular tension caused by noradrenaline (NA) in mesenteric arteries was measured with a sensitive myograph system. The serum levels of oxLDL, TNF-alpha, and IL-1 beta were detected using enzyme linked immunosorbent assays. The expressions of the at adrenoceptor, the alpha(2) adrenoceptor, INF-alpha, IL-1 beta, and pERK1/2 were detected using real-time polymerase chain reactions and Western blot analysis. Compared with the NS group, the mmLDL group exhibited a noticeably enhanced NA shrinkage dose-response curve and a significantly increased E-max value (P < 0.01). Prazosin (alpha(1) adrenoceptor antagonist) caused a noticeable right shift of the dose-response curve. U0126 inhibited the increases in the serum levels and vessel wall expression of IL-1 beta and TNF-alpha and enhanced the NA shrinkage dose-response curve caused by mmLDL, as observed by a significantly decreased E-max value (P < 0.01). It inhibited the increased at adrenoceptor expression caused by mmLDL. The serum levels of IL-1 beta and TNF-alpha demonstrated a positive correlation with the NA-induced maximum shrinkage percentage. U0126 inhibited the mmLDL-induced increase in the pERK1/2 protein level in the vessel wall. In conclusion, mmLDL increased the serum levels of IL-1 beta and TNF-alpha in vivo by activating the ERK1/2 pathway, which resulted in alpha(1) receptor-mediated vasoconstriction and an increase in the expression of alpha(1) adrenoceptor. The results of this study may provide new ideas for the prevention and cure of cardiovascular diseases in the future. (C) 2015 Elsevier Inc. All rights reserved.
摘要：
Apelin is highly expressed in rat left ventricular hypertrophy Sprague Dawley rat models, and it plays a crucial role in the cardiovascular system. The aim this study was to clarify whether apelin-13 promotes hypertrophy in H9c2 rat cardiomyocytes and to investigate its underlying mechanism. The cardiomyocyte hypertrophy was observed by measuring the diameter, volume, and protein content of H9c2 cells. The activation of autophagy was evaluated by observing the morphology of autophagosomes by transmission electron microscopy, observing the subcellular localization of LC3 by light microscopy, and detecting the membrane-associated form of LC3 by western blot analysis. The phosphatidylinositol 3-kinase (PI3K) signaling pathway was identified and the proteins expression was detected using western blot analysis. The results revealed that apelin-13 increased the diameter, volume, and protein content of H9c2 cells and promoted the phosphorylation of PI3K, Akt, ERK1/2, and p70S6K. Apelin-13 activated the PI3K-Akt-ERK1/2-p70S6K pathway. PI3K inhibitor LY294002, Akt inhibitor 1701-1, ERK1/2 inhibitor PD98059 attenuated the increase of the cell diameter, volume, protein content induced by apelin-13. Apelin-13 increased the autophagosomes and up-regulated the expressions of beclin 1 and LC3-II/I both transiently and stably. The autophagy inhibitor 3MA ameliorated the increase of cell diameter, volume, and protein content that were induced by apelin-13. These results suggested that apelin-13 promotes H9c2 rat cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy.
