内皮细胞损伤与修复的研究进展

内皮细胞是重要代谢和内分泌器官,在调节血管功能中起重要作用。多种心脑血管疾病(如动脉粥样硬化、高血压、糖尿病血管并发症等)的发生发展与内皮损伤密切相关。然而血管内皮细胞损伤的机制尚未完全明了。大量研究表明,内皮细胞损伤机制主要涉及炎症反应和氧化应激。内皮祖细胞在修复损伤内皮过程中发挥重要作用。多种化学药物和中药,通过减少诱发因素、抑制炎症反应与氧化应激反应、延缓内皮细胞衰老等途径发挥内皮保护作用。     

高胆固醇血症患者血管内皮功能改变及降脂干预治疗

正常血管内皮的主要功能是抑制与动脉粥样硬化有关的血管平滑肌收缩、血小板聚集、血管平滑肌细胞增生、白细胞粘附和血栓形成。内皮细胞损伤时，内皮功能失调，其抑制作用减弱或消失，其导致的缩血管物质释放增多、粘附分子表达、血小板聚集等均可促进动脉粥样硬化形成。许多研究表明，内皮细胞产生的血管活性物质，如一氧化氮(NO)、内皮素(ET)、     

抵抗素对动脉硬化和心脏疾病的影响

抵抗素是脂肪细胞分泌的一种多肽类激素。越来越多研究表明抵抗素可以促进C反应蛋白,肿瘤坏死因子α、白细胞介素6等炎症标志物的表达,诱导血管炎症反应的发生,从而损伤血管内皮细胞以及平滑肌细胞并影响其功能。本文就抵抗素与动脉粥样硬化及心血管疾病相互关系的研究现状做一综述。     

辛伐他汀对人脐静脉内皮细胞血管内皮生长因子表达的影响

采用逆转录聚合酶链反应和Western Blot方法，观察促炎症因子肿瘤坏死因子α和白细胞介素1β对体外培养人脐静脉内皮细胞血管内皮生长因子及其受体表达的影响，并以辛伐他汀干预，观察其对上述过程的影响。结果发现，肿瘤坏死因子α和白细胞介素1β显著促进人脐静脉内皮细胞中血管内皮生长因子及其受体的表达，在不同水平辛伐他汀对促炎症因子的上述作用具有一定的抑制效应，由此推断辛伐他汀可能具有一定的抗炎症反应及抗动脉粥样硬化的作用。     

以白细胞介素1β为靶点治疗动脉粥样硬化研究进展

近来的研究表明动脉粥样硬化本质上是一种血管的慢性炎症反应性疾病,白细胞介素1β在其发展过程中起到关键性调节作用。血管内各种因素导致的内皮细胞损伤可导致白细胞介素1β的大量表达,通过与白细胞介素1Ⅰ型受体结合并激活NF-κB信号通路,诱导二级炎性调节物白细胞介素6、肿瘤坏死因子α等大量生成。动物实验及临床实验结果表明拮抗白细胞介素1β信号通路有利于改善心肌重构,降低动脉粥样硬化所致心血管事件发病风险,以白细胞介素1β为靶点治疗动脉粥样硬化具有良好的临床应用前景。     

抵抗素参与血管内皮细胞功能障碍的研究进展

抵抗素是脂肪细胞分泌的一种多肽类激素,早有研究证明抵抗素通过影响胰岛素信号转导参与了胰岛素抵抗,与2型糖尿病的发生发展密切相关.越来越多研究表明抵抗素可以促进肿瘤坏死因子α、白细胞介素6等炎症标志物的表达,诱导血管炎症反应的发生,从而损伤血管内皮细胞并影响其功能.内皮细胞功能异常又是动脉粥样硬化及糖尿病血管并发症病理过程的始动环节,提示抵抗素可能在心血管疾病的发生发展中起重要作用.本文就有关抵抗素参与血管内皮细胞功能障碍的研究进展作一综述.     

丹参川芎嗪注射液对TNFα干预血管内皮细胞损伤ET-1和ICAM-1基因表达的影响

动脉粥样硬化(AS)是一种慢性炎症性疾病,各种危险因素引起细胞释放肿瘤坏死因子(TNF)和白细胞介素等细胞因子作用在内皮细胞上,内皮素(ET)的分泌增加导致内皮细胞功能受损,内皮细胞上的细胞间黏附因子(ICAM)-1表达增加,导致单核细胞黏附在血管内皮细胞上,进一步的促使AS发生和发展.活血化瘀中药具有抗血管内皮损伤、防治AS的作用[1].采用活血化瘀法干预AS的发生发展能够取得良好的效果[2].丹参川芎嗪注射液是根据中医活血化瘀的原理,以丹参和川芎为主的中草药经过现代科学技术方法加工制成,其主要成分为丹参素和川芎嗪.临床广泛应用于闭塞性脑血管疾病,如脑供血不足、脑血栓形成、脑栓塞及其他缺血性心血管疾病,如冠心病的胸闷、心绞痛、心肌梗死、缺血性脑卒中、血栓闭塞性脉管炎等的治疗当中.本文采用炎症因子TNF-α干预致人脐静脉内皮细胞ECV304损伤,模拟AS时血管内皮受损的情况,探讨丹参川芎嗪注射液对与内皮细胞功能密切相关的ET-1和ICAM-1表达的影响.     

动脉粥样硬化性心血管病炎症的临床评价和治疗

血管内皮细胞功能紊乱和炎症在动脉粥样硬化及其相关疾病的进展中起重要作用,C反应蛋白、高灵敏C反应蛋白、细胞黏附因子、白细胞介素和斑块温度及斑块pH变化参与动脉粥样硬化炎症过程。现对这些炎症标志物在动脉粥样硬化炎症中的临床评价及其药物干预研究进展做一复习。     

血管内皮细胞功能障碍与动脉粥样硬化关系的研究进展

血管内皮细胞损伤、内皮功能障碍是动脉粥样硬化的起始环节,其参与动脉粥样硬化的启动和进展过程。内皮功能障碍及形态学损伤引起白细胞-内皮细胞黏附、血管收缩、血小板聚集、氧化应激、平滑肌增殖及血栓形成。内皮细胞功能调节与多种相关因子之间的作用机制是复杂的,本文以内皮细胞功能障碍与动脉粥样硬化关系为切入点,综述血管内皮细胞功能与动脉粥样硬化发生发展的研究进展。     

内皮微粒与冠心病

完整的单层内皮细胞屏障在维持血管的正常结构、功能及抗粥样硬化中起着关键作用。内皮细胞通过释放抗凝、抗炎物质及扩张血管等作用起到抗动脉粥样硬化作用。当内皮细胞激活、损伤和（或）凋亡时,向细胞外释放内皮微粒（EMP）。EMP可以促进血栓形成和炎症反应,影响血管内皮功能,并且在动脉粥样硬化、冠心病、冠心病危险因素（如高血压、吸烟、代谢综合征和糖尿病）等状态下,其体内水平明显升高。     

Tetrahydrobiopterin: regulator of endothelial nitric oxide synthase in vascular disease

In vascular disease states such as atherosclerosis and diabetes, endothelial nitric oxide (NO) bioactivity is reduced and oxidative stress is increased, resulting in endothelial dysfunction. Recent studies suggest that changes in the activity and regulation of endothelial NO synthase by its cofactor tetrahydrobiopterin (BH4) is an important contributor to endothelial dysfunction. Pharmacologic studies and more recent insights from genetically modified mouse models have improved the understanding of the mechanistic role and importance of BH4 in vascular disease pathogenesis. Targeting BH4 may provide new therapeutic strategies in vascular disease.     

Oxidative stress and atherosclerosis

Understanding of the pathophysiology of atherosclerosis can provide new strategies for the prevention and treatment of patients with this common disease. Clinical, epidemiologic, and basic molecular science studies have identified oxidative stress as a factor contributing to the development and progression of atherosclerosis. Oxidative stress also participates in the pathogenesis of endothelial dysfunction and hypertension, two important factors in many patients with atherosclerosis. Further, it contributes to mechanisms of disease progression such as lipid oxidation and vascular remodeling. This article reviews the role of reactive oxygen species and oxidative stress in atherosclerosis.     

Coronary risk factors,endothelial function,and atherosclerosis: A review

The traditional risk factors for coronary heart disease, which include hypercholesterolemia, hypertension, cigarette smoking, diabetes mellitus, and high-fat diet, have all been associated with impairments in endothelial function. Impaired endothelium function may promote the development of atherosclerosis through its effects on vasoregulation, platelet and monocyte adhesion, vascular smooth muscle cell growth, and coagulation. Increased oxidative stress may be another mechanism by which endothelial dysfunction contributes to atherosclerosis, although controversy exists on this issue. Risk factor modification, particularly lowering elevated concentrations of low-density lipoprotein cholesterol, improves endothelial function. At least seven clinical studies have demonstrated improved endothelial function with cholesterol reductions in patients with markedly elevated or even borderline elevations in cholesterol concentrations, whether or not coronary heart disease is present. Other interventions that improve endothelial function include blood pressure reduction, smoking cessation, and administration of estrogen to postmenopausal women.     

线粒体自噬和内质网应激调控血管内皮细胞功能研究进展

血管内皮细胞在调节人体血液循环功能、维持人体心血管系统稳定及促进血管结构重塑中发挥着重要作用.近年来的研究成果证实,线粒体自噬与人体血管壁、内皮组织细胞氧化稳态和细胞氧化应激机制关系密切.内质网是一种维持人体细胞内部结构和生理功能的重要亚特性细胞器,参与人体细胞的众多自然生理化学活动.多种细胞刺激化学因素作用造成的内质...     

Obstructive sleep apnea: an emerging risk factor for atherosclerosis

Obstructive sleep apnea (OSA) is independently associated with death from cardiovascular diseases, including myocardial infarction and stroke. Myocardial infarction and stroke are complications of atherosclerosis; therefore, over the last decade investigators have tried to unravel relationships between OSA and atherosclerosis. OSA may accelerate atherosclerosis by exacerbating key atherogenic risk factors. For instance, OSA is a recognized secondary cause of hypertension and may contribute to insulin resistance, diabetes, and dyslipidemia. In addition, clinical data and experimental evidence in animal models suggest that OSA can have direct proatherogenic effects inducing systemic inflammation, oxidative stress, vascular smooth cell activation, increased adhesion molecule expression, monocyte/lymphocyte activation, increased lipid loading in macrophages, lipid peroxidation, and endothelial dysfunction. Several cross-sectional studies have shown consistently that OSA is independently associated with surrogate markers of premature atherosclerosis, most of them in the carotid bed. Moreover, OSA treatment with continuous positive airway pressure may attenuate carotid atherosclerosis, as has been shown in a randomized clinical trial. This review provides an update on the role of OSA in atherogenesis and highlights future perspectives in this important research area.     

Modification of environmental toxicity by nutrients

We hypothesize that nutrition can modulate the toxicity of environmental pollutants and thus modulate health and disease outcome associated with chemical insult. There is now increasing evidence that exposure to persistent organic pollutants, such as PCBs, can contribute to the development of inflammatory diseases such as atherosclerosis. Activation, chronic inflammation, and dysfunction of the vascular endothelium are critical events in the initiation and acceleration of atherosclerotic lesion formation. Our studies indicate that an increase in cellular oxidative stress and an imbalance in antioxidant status are critical events in PCB-mediated induction of inflammatory genes and endothelial cell dysfunction. Furthermore, we have found that specific dietary fats can further compromise endothelial dysfunction induced by selected PCBs and that antioxidant nutrients (such as vitamin E and dietary flavonoids) can protect against endothelial cell damage mediated by these persistent organic pollutants. Our recent data suggest that membrane lipid rafts such as caveolae may play a major role in the regulation of PCB-induced inflammatory signaling in endothelial cells. In addition, PCB- and lipid-induced inflammation can be down-regulated by ligands of anti-atherogenic peroxisome proliferator-activated receptors (PPARs). We hypothesize that PCBs contribute to an endothelial inflammatory response in part by down-regulating PPAR signaling. Our data so far support our hypothesis that antioxidant nutrients and related bioactive compounds common in fruits and vegetables protect against environmental toxic insult to the vascular endothelium by down-regulation of signaling pathways involved in inflammatory responses and atherosclerosis. Even though the concept that nutrition may modify or ameliorate the toxicity of environmental chemicals is provocative and warrants further study, the implications for human health could be significant. More research is needed to understand observed interactions of PCB toxicity with nutritional interventions.     

Mitochondrial dysfunction in atherosclerosis

Increased production of reactive oxygen species in mitochondria, accumulation of mitochondrial DNA damage, and progressive respiratory chain dysfunction are associated with atherosclerosis or cardiomyopathy in human investigations and animal models of oxidative stress. Moreover, major precursors of atherosclerosis-hypercholesterolemia, hyperglycemia, hypertriglyceridemia, and even the process of aging-all induce mitochondrial dysfunction. Chronic overproduction of mitochondrial reactive oxygen species leads to destruction of pancreatic beta-cells, increased oxidation of low-density lipoprotein and dysfunction of endothelial cells-factors that promote atherosclerosis. An additional mechanism by which impaired mitochondrial integrity predisposes to clinical manifestations of vascular diseases relates to vascular cell growth. Mitochondrial function is required for normal vascular cell growth and function. Mitochondrial dysfunction can result in apoptosis, favoring plaque rupture. Subclinical episodes of plaque rupture accelerate the progression of hemodynamically significant atherosclerotic lesions. Flow-limiting plaque rupture can result in myocardial infarction, stroke, and ischemic/reperfusion damage. Much of what is known on reactive oxygen species generation and modulation comes from studies in cultured cells and animal models. In this review, we have focused on linking this large body of literature to the clinical syndromes that predispose humans to atherosclerosis and its complications.     

Oxidation of chylomicron remnants and vascular dysfunction

Recent evidence suggests that chylomicron remnants (CMRs), the lipoproteins which carry dietary lipids in the blood, may play a direct role in the initiation of atherosclerosis by influencing vascular function. Unlike low-density lipoprotein (LDL), CMR do not require prior oxidation to bring about potentially pro-atherogenic effects on vascular endothelial cell function and macrophage foam cell formation. However, CMR carry oxidized lipids from the diet and may also become oxidized in the body, thus it is important to establish how the oxidative state of the particles may modulate these effects. Pharmacological studies have demonstrated that oxidation of CMR significantly enhances their inhibitory effects on endothelium-dependent vascular relaxation and their potentiation of vasoconstriction in rat and pig arteries. In striking contrast to the effects of LDL oxidation, however, the induction of macrophage foam cell formation has been found to be inversely related to the oxidative state of CMR. Thus, oxidation of CMR has potentially pro-atherogenic effects on endothelial function, but appears to protect against foam cell generation. These findings indicate that the oxidative state of CMR may cause important changes in the atherogenicity of the particles.