高血压机械力诱导血管平滑肌细胞结构与功能变化及其在血管疾病中的作用

血压升高产生的机械力在血管分化与发育、血管正常结构与功能维持以及血管病变过程中起决定作用,血脂和/或血糖异常升高可协同机械力作用加速血管重构及疾病发生发展。机械力可非特异性激活血管细胞所有跨膜蛋白分子,引起细胞内多信号通道分子(第二效应分子)同步活化。多通道信号分子在信号网络结点分子汇集,继而再散发,启动更多信号通路活化,实现信号的级联瀑布放大,导致细胞一系列病理生理学变化如细胞分化、迁移、炎症、表型变化、钙化、增殖、凋亡等,最终引起血管的结构与功能改变如动脉粥样硬化等,成为心脑血管疾病致死、致残的主要原因。本文对本课题组及国际同行相关研究进展,亦即血压升高产生的机械力对血管平滑肌细胞作用相关的血管重构做一简要综述。     

中医药干预肺血管衰老的研究进展与展望

机体衰老是一个动态的和时间顺序的进程,其特征是细胞损伤逐渐累积,功能逐渐衰退,对疾病的易感性增加。血管衰老是整体衰老的基本组成,包括内皮功能障碍、血管舒张受损、细胞外基质重塑、内膜弥漫性增厚和动脉僵硬度增加等改变,加速血管相关疾病的发生与发展[1]。血管衰老的准确定义尚不十分明确[2]。血管衰老常被认为是以生理性变化为基础,叠加各种疾病或危险因素的影响而出现的结构和功能的改变。它既有生理性的成分,也有病理性的成分。     

速度向量成像在评估血管老化相关疾病中的应用

血管老化指血管结构和功能退行性改变。速度向量成像根据斑点追踪技术,通过对血管精确定位,立体评估不同方向的速度、应变及应变率,能全面评估血管老化过程中力学特点、管壁功能,在血管老化相关疾病的早期检查和治疗中起着重要作用。现简述该技术在评估血管老化过程及相关疾病包括高血压、糖尿病及动脉粥样硬化中的应用。     

外泌体microRNA在血管老化及其相关性疾病中的作用

血管老化是指血管结构和功能随增龄而发生的退行性改变,其影响多种疾病的发生、进展和预后。血管内皮细胞和血管平滑肌细胞是构成血管壁的主要细胞,是血管老化的重要细胞生物学基础。近年来,外泌体微小RNA(miRNA)与血管老化的关系成为研究热点。本综述将总结外泌体miRNA在血管内皮细胞和平滑肌细胞衰老过程中的作用,同时讨论外泌体miRNA在血管老化相关性疾病中的功能。     

高密度脂蛋白组分:心血管疾病诊治的新靶点

血浆高密度脂蛋白是由载脂蛋白、脂质及多种功能蛋白质共同组成的复合物。它可通过促进胆固醇逆转运、抗氧化、抗炎症反应及血管内皮保护等作用抑制动脉粥样硬化。高密度脂蛋白生理功能的发挥依赖于其组成成分和水平的正常。疾病时,高密度脂蛋白组分的异常修饰,或其含量及活性的变化均可导致其上述功能的改变,甚至使之转变成为促动脉粥样硬化性物质。因此,探明对高密度脂蛋白功能起关键作用的组分及疾病特异性组分变化可为心血管疾病的诊断和治疗提供新的靶点。     

肺栓塞的病理生理

肺栓塞是内源性或外源性栓子堵塞肺动脉或其分支引起肺循环障碍的临床和病理生理综合征。目前对肺栓塞的病理生理学改变已有广泛研究 ,其病理生理学变化复杂多变 ,主要是影响呼吸系统、血流动力学[1 4 ] 及血管内皮功能[5,6 ] ,从而产生一系列心肺功能异常及血管内皮功能改变。影响程度主要取决于既往是否患有心肺血管疾病、肺动脉堵塞的范围及速度。一、血流动力学改变及血管内皮功能影响发生急性肺栓塞时 ,栓子堵塞肺动脉 ,造成机械性肺毛细血管前动脉高压 ,肺血管床减少 ,肺循环阻力增加 ,肺动脉压力上升 ,右心室负荷增加 ,心输出量下降…     

中性粒细胞淋巴细胞比值与OPCABG术后新发房颤相关性研究

原发性高血压是由遗传和环境等多种因素共同作用导致的疾病,有研究表明血管内皮功能障碍是原发性高血压发病机制中的重要环节。细胞外囊泡（Extracellular Vehicles, EVs）是体液环境中存在的一种包含核酸、蛋白质等成分的脂质体,具有在细胞间信息交换的功能。EVs能够影响靶细胞的表型和功能,参与多种疾病的病理生理过程。有研究显示EVs可能在血压调节中发挥重要作用,介导血管内皮功能的变化。EVs参与细胞免疫及体液免疫造成的血管内皮损伤过程,刺激血管内皮分泌促炎症因子,损伤血管的舒张功能。同时EVs刺激内皮细胞中活性氧物质水平的增加,减少一氧化氮的产生及降低其生物利用度,直接影响内皮细胞依赖的血管舒张功能,引起血压升高。本文总结了EVs在原发性高血压血管内皮损伤中的作用,提示EVs参与原发性高血压的发生发展过程,为进一步深化高血压发病机制的相关研究提供参考。     

糖尿病患者的N-糖组学研究进展

N-糖组学主要是研究机体内N-聚糖结构和功能的一门新兴学科, 近年来N-糖组改变与各种疾病相关性研究日益增多。糖尿病是世界范围内发病率较高的慢性疾病, 糖尿病患者体内普遍出现多种病理生理学变化及代谢紊乱, 以糖代谢紊乱最为突出。目前有较多研究报道, 糖尿病与N-糖组改变相关, 糖尿病患者血清中N-糖蛋白的数量、结构和免疫球蛋白G N-聚糖发生了改变, 并表明N-聚糖有可能作为糖尿病生物标志物。该文就目前糖尿病的N-糖组学相关研究进展作一简要综述。     

高血压病对认知功能影响的研究进展

由于人口老龄化、人口结构变化和缺乏疾病矫正治疗等原因,认知障碍的人数不断增加,且高血压对认知功能的影响越来越受到重视。在老年人群中,不同认知域评估和不同随访设计的临床研究结果显示高血压对认知功能影响并不一致,其作用机制尚不明确。现从流行病学调查结果,就高血压通过血管紧张素系统、动脉粥样硬化、炎症和氧化应激等方面对脑血管结构、功能改变和血脑屏障障碍方面进行讨论以阐述其对认知功能的可能影响。     

微粒在慢性气道炎症性疾病中的作用

研究表明微粒作为细胞间信号转导的载体,在多种疾病中起着重要作用。它通过对细胞的内分泌、分子信号转导、物质合成等生物功能的调节而影响组织的损伤、修复,参与疾病的发生、发展。在病理状态下,微粒数量增多、内容物发生改变,影响靶细胞的物质代谢、能量代谢,导致靶细胞结构、功能改变,从而引起组织、器官结构功能改变,导致疾病发生。而慢性气道炎症性疾病是以气道阻塞、气道重塑为主要特征的疾病,气道的慢性炎症是其基本特点,越来越多的证据表明微粒与气道慢性炎症性疾病的发生、发展有着密切联系,在气道上皮的损伤与修复过程中起着关键性作用。该综述将阐述微粒在支气管哮喘、COPD 等疾病进程中的作用,以期通过对微粒产生及作用机制的了解,帮助寻找疾病诊疗的新策略。     

机械力信号与部分心血管疾病的发生

机械力信号对多种心血管疾病有着重要的调控作用。机械应力可分为拉伸应力和剪切应力,拉伸应力可影响血管中所有类型的细胞,而剪切应力主要影响内皮细胞,它们通过机械传感器的作用引起细胞内化学信号的变化,从而调控各种生命活动。剪切应力可通过调控炎症相关信号通路调节动脉粥样硬化以及冠心病的发生;各种机械应力可通过调控血管内皮细胞、平滑肌细胞增殖,诱导细胞外基质纤维化,从而增加血压,调节肺动脉高压的发生。并通过调控MAPK、JAK/STAT等信号途径从而调节心脏肥大的发生。文章旨在探究机械力信号与部分心血管疾病发生发展的关系,阐明机械力信号诱发这些心血管疾病的分子机制,从而加深对这些心血管疾病发生发展的认识,为其治疗提供更广的思路。     

Statins and hypertension

Hypertension and dyslipidemia are frequently associated as risk factors for cardiovascular diseases. Statins are among the most potent drugs to correct hypercholesterolemia, and their use across a wide range of cardiovascular risk levels significantly reduced morbidity and mortality in large intervention trials. Aside from (or in addition to) reducing plasma cholesterol, statins also reduce blood pressure, another effect associated with cardiovascular risk reduction by other antihypertensive drugs. This review examines the proposition that a part of the statins' beneficial effect in cardiovascular diseases may result from direct effects on blood pressure regulation, perhaps independent of lipid lowering. Potential molecular mechanisms are considered (e.g., "pleiotropic" effects on endothelial vasoactive mediators, oxidant stress, or inflammation), all of which may affect the central or peripheral control of blood pressure homeostasis, as well as modulate target organ damage. In particular, potential effects of statins on blood pressure and heart rate variability open new perspectives for a better tailoring of drug treatment in high-cardiovascular risk patients.     

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

In humans and most animal models, the development of obesity leads not only to increased fat depots in classical adipose tissue locations but also to significant lipid deposits within and around other tissues and organs, a phenomenon known as ectopic fat storage. The purpose of this review is to explore the possible locations of ectopic fat in key target-organs of cardiovascular control (heart, blood vessels and kidneys) and to propose how ectopic fat storage can play a role in the pathogenesis of cardiovascular diseases associated with obesity. In animals fed a high-fat diet, cardiac fat depots within and around the heart impair both systolic and diastolic functions, and may in the long-term promote heart failure. Accumulation of fat around blood vessels (perivascular fat) may affect vascular function in a paracrine manner, as perivascular fat cells secrete vascular relaxing factors, proatherogenic cytokines and smooth muscle cell growth factors. Furthermore, high amounts of perivascular fat could mechanically contribute to the increased vascular stiffness seen in obesity. Finally, accumulation of fat in the renal sinus may limit the outflow of blood and lymph from the kidney, which would alter intrarenal physical forces and promote sodium reabsorption and arterial hypertension. Taken together, ectopic fat storage in key target-organs of cardiovascular control may impair their functions, contributing to the increased prevalence of cardiovascular diseases in obese subjects.     

高密度脂蛋白结构、代谢和功能研究新进展

高密度脂蛋白(HDL)主要由载脂蛋白A1(ApoA1)、脂质以及相关的调节因子组成,其结构及功能异常与心血管疾病的发生、发展密切相关。HDL主要通过胆固醇逆向转运途径将血管内皮下巨噬细胞内胆固醇运送至肝脏并排出,调节体内的脂质平衡。研究发现,心血管疾病患者体内HDL的结构及代谢方式发生变化,包括ApoA1的异常修饰、血清淀粉样蛋白A取代ApoA1、HDL运载的miRNA含量变化。本文就HDL的结构、代谢和功能进行综述,为脂质代谢相关疾病的诊断和治疗提供新的思路。     

The mitochondrial organelle and the heart

The heart is highly dependent for its function on oxidative energy generated in mitochondria, primarily by fatty acid beta-oxidation, respiratory electron chain and oxidative phosphorylation. Defects in mitochondrial structure and function have been found in association with cardiovascular diseases such as dilated and hypertrophy cardiomyopathy, cardiac conduction defects and sudden death, ischemic and alcoholic cardiomyopathy, as well as myocarditis. While a subset of these mitochondrial abnormalities have a defined genetic basis (e.g. mitochondrial DNA changes leading to oxidative phosphorylation dysfunction,fatty acid beta-oxidation defects due to specific nuclear DNA mutations), other abnormalities appear to be due to a more sporadic or environmental cardiotoxic insult or have not yet been characterized.This review focuses on abnormalities in mitochondrial bioenergetic function and mitochondrial DNA defects associated with cardiovascular diseases, their significance in cardiac pathogenesis as well as on the available diagnostic and therapeutic options. A concise background concerning mitochondrial biogenesis and bioenergetic pathways during cardiac growth,development and aging will also be provided.     

β3肾上腺素能受体在心血管疾病中的研究进展

交感神经系统（sympatheticnervoussystem,SNS）是心血管神经体液调节的核心,而其释放的儿茶酚胺（catecholamines,CA）涉及许多心血管疾病。目前认为β1和β2肾上腺素能受体（adrenergicreceptors,AR）介导心肌对于CA的收缩效应以及血管平滑肌的舒张反应。然而,1989年发现了第3种β-AR亚型即β3-AR的分子特征,随后在人类心脏得以克隆,这些研究改变了β—AR系统调节心脏功能的经典模式。在血管中,激动β3-AR可产生舒张效应,但目前对于β3-AR的病理生理作用尚未完全明了。本综述主要阐述β3-AR在心血管系统功能作用的分子机制,以及β3-AR在几种常见心血管疾病中的潜在作用和将其作为新的治疗靶点的药理学机制。     

Androgen actions on endothelium functions and cardiovascular diseases

The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple factors such as genetic and epigenetic variation, sex-specificity, hormone interactions, drug preparation and route of administration may contribute. Recently, growing evidence suggests that androgens exhibit beneficial effects on cardiovascular function though the mechanism remains to be elucidated. Endothelial cells (ECs) which line the interior surface of blood vessels are distributed throughout the circulatory system, and play a crucial role in cardiovascular function. Endothelial progenitor cells (EPCs) are considered an indispensable element for the reconstitution and maintenance of an intact endothelial layer. Endothelial dysfunction is regarded as an initiating step in development of atherosclerosis and cardiovascular diseases. The modulation of endothelial functions by androgens through either genomic or nongenomic signal pathways is one possible mechanism by which androgens act on the cardiovascular system. Obtaining insight into the mechanisms by which androgens affect EC and EPC functions will allow us to determine whether androgens possess beneficial effects on the cardiovascular system. This in turn may be critical in the prevention and therapy of cardiovascular diseases. This article seeks to review recent progress in androgen regulation of endothelial function, the sex-specificity of androgen actions, and its clinical applications in the cardiovascular system.     

Retinal vascular manifestations of metabolic disorders.

Metabolic diseases have profound effects on the structure and function of the retinal circulation. The recent development of retinal photography and digital imaging has enabled more precise documentation of diabetic retinopathy, as well as other retinal microvascular changes, such as retinal arteriolar narrowing, venular dilation and isolated retinopathy signs in nondiabetic individuals. These retinal microvascular signs have been shown to be associated with long-term risks of type 2 diabetes and hypertension, components of the metabolic syndrome (e.g. obesity, dyslipidemia), and a range of macro- and micro-vascular conditions (e.g. stroke, cardiovascular mortality). There is evidence that endothelial dysfunction and inflammation might be possible mechanisms involved in the development of various retinal microvascular changes in patients with diabetes, hypertension and other metabolic disorders. Further understanding of how these processes influence the retinal vasculature might help to elucidate the diverse vascular manifestations of metabolic diseases.     

Koronare Mikrozirkulation

The coronary microcirculation does not only control perfusion of the myocardium, but also plays an important role for the manifestation of ischemic heart disease throughout all stages of the disease. Risk factors for coronary artery disease are associated with a reduced endothelium-dependent blood flow regulation, which not only may aggravate myocardial ischemia but also determines blood flow-induced shear stress exposed to the vascular wall, modulating the vascular milieu (e. g., by controlling nitric oxide bioactivity) and thereby altering progression of atherosclerosis in conductance vessels. Furthermore, generally impaired microvascular function is predictive of cardiovascular events, e. g., after percutaneous coronary interventions or after an acute myocardial infarction. In the latter case, thrombotic embolism from ruptured plaques in the conductance vessels as well as inflammation and reperfusion injury are the essential components of the microvascular disorder. Interestingly, therapeutic strategies which improve microvascular dysfunction, such as statins in stable coronary artery disease or glycoprotein IIb/IIIa inhibitors during acute myocardial infarction, are associated with an improved long-term prognosis. These facts give promise for new therapeutic principles: experimental data demonstrate, that the therapeutic application of stem or progenitor cells after an acute myocardial infarction induces growth of new microvessels (neovascularization) and thereby improves microvascular perfusion, which may favorably alter infarct expansion and remodeling. First clinical data, demonstrating indeed an improved coronary blood flow regulation after progenitor cell therapy in patients with ischemic heart disease, have to be established by further clinical trials.