Endothelial progenitors

The studies carried out during the last two decades have represented a great effort in trying to identify and define cell populations endowed with the phenotypic and functional properties of endothelial progenitors. From these studies a scenario now emerges indicating that in the blood there are very rare endothelial progenitor cells, called endothelial colony-forming cells (ECFCs) or late outgrowth endothelial cells, not originated from bone marrow, capable of generating phenotypically and functionally competent endothelial cells, capable to be incorporated in vivo into growing vessels. ECFCs are present in the circulation as well as cells resident in the vascular endothelial intima. In addition to these progenitors, there are some hematopoietic progenitor cells capable of generating a monocytic cell progeny exerting a pro-angiogenic activity in vivo, but unable to be directly incorporated into growing vessels. These cells exert a pro-angiogenic effect in vivo through a paracrine mechanism based on the secretion of growth factors and cytokines.     

Endothelial aging

Aging is considered to be the major risk factor for the development of atherosclerosis and, therefore, for coronary artery disease. Apart from age-associated remodeling of the vascular wall, which includes luminal enlargement, intimal and medial thickening, and increased vascular stiffness, endothelial function declines with age. This is most obvious from the attenuation of endothelium-dependent dilator responses, which is a consequence of the alteration in the expression and/or activity of the endothelial NO synthase, upregulation of the inducible NO synthase, and increased formation of reactive oxygen species. Aging is also associated with a reduction in the regenerative capacity of the endothelium and endothelial senescence, which is characterized by an increased rate of endothelial cell apoptosis.     

Circulating Endothelial Cells and Endothelial Progenitor Cells in Obstructive Sleep Apnea

Increased circulating endothelial cells (CECs) have been observed in patients with vascular injury associated with acute myocardial infarction, pulmonary hypertension, and congestive heart failure. Decreased circulating endothelial progenitor cells (EPCs) have been observed in patients with risk factors for cardiovascular disease. Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular disease and endothelial dysfunction. Subjects were recruited from patients referred for overnight polysomnograms; 17 subjects had OSA and 10 control subjects did not have OSA. All subjects lacked vascular disease and risk factors for vascular disease. Peripheral blood was obtained from fasting subjects in the morning, following sleep studies. CECs and EPCs were quantified using magnetic bead separation with UV epifluorescence microscopy and flow cytometry immunophenotyping, respectively. Cell counts and demographic variables were compared using unpaired t tests. Regression analysis was performed comparing cell counts with the apnea-hypopnea index (AHI) and nadir SaO(2). Subjects with OSA and controls did not differ significantly in terms of age and body mass index. Subjects with OSA had higher AHI, lower nadir SaO(2), and greater sleepiness (Epworth Sleepiness Scale scores). There were no significant differences in CEC (7.0+/-1.5 vs. 4.9+/-0.9, p>0.05) or EPC (1077+/-318 vs. 853+/-176, p>0.05) between controls and OSA cases, respectively. In this small study, we found no differences in CECs or circulating EPCs between patients with OSA and controls. OSA may not be associated with these markers of vascular endothelial cell injury in patients with no concomitant vascular disease.     

体外反搏对冠心病患者血管内皮及其功能的影响

目的:通过增强型体外反搏治疗经皮冠状动脉腔内成形和支架置入术后的冠心病患者,观察对血管内皮舒张功能影响,以及是否会对血管内皮造成损伤。方法:将51例冠心病患者(均为经皮冠状动脉腔内成形和支架置入术后)分成两组,按1:2匹配,反搏组17例,对照组34例。两组均给予常规药物治疗,此外反搏组予以3个疗程的体外反搏治疗。血流介导的血管舒张反应(FMD)和硝酸甘油介导的血管舒张反应(NMD)采用Celermajer法;高敏C反应蛋白(hsCRP)的检测采用免疫比浊法。结果:对照组治疗后FMD、NMD、hsCRP较治疗前无明显变化(P＞0.05),反搏组治疗后FMD明显升高(P＜0.01), NMD也有升高(P＜0.05),hsCRP无明显变化(P＞0.05);组间比较发现,反搏组FMD和NMD的提高程度较对照组明显(P＜0.01),两组间hsCRP的改变无明显差异(P＞0.05)。结论:增强型体外反搏通过提高对血管壁内皮细胞的切应力,改善了经皮冠状动脉腔内成形和支架置入术后冠心病患者的内皮功能,使血管的舒张功能增加,且没有造成血管内皮的损伤,为冠心病患者的综合治疗提供了实验依据。     

衰老与血管内皮功能障碍

血管内皮功能障碍是血管老化的早期病理改变之一,对动脉粥样硬化的发生发展起到非常重要的作用。老年性血管内皮功能障碍主要表现在内皮一氧化氮、前列环素和内皮衍生超极化因子等一系列内皮舒血管物质的生成减少或其生物利用度下降,而内皮素、血栓素和活性氧等一些内皮缩血管物质的生成或血管对这些物质的敏感性增加。另外,衰老导致的血管内皮修复能力减退也起到一定的作用。现就衰老对这些因素的影响及其分子机制作一概述。     

内皮功能障碍及治疗对策

内皮功能障碍在心血管疾病的发病机制中起着重要作用。本文复习近期国内外文献 ,对内皮功能障碍的危险因素及治疗对策做一综述。     

Endothelial heterogeneity and plasticity

Angiogenesis - Vascular endothelial cells are highly plastic and show great phenotypic heterogeneity. In recent years, emerging technologies have identified a range of novel endothelial phenotypes...     

内皮源性微粒的多面性

内皮源性微粒是具有复杂的囊泡性结构,来源于激活或凋亡的内皮源性细胞。它们在凝血、炎症、内皮功能和血管新生中具有显著的作用,干扰血管的动态平衡,促进血管相关性疾病形成。在血管性疾病患者中,内皮源性微粒水平增高,它们能作为反应内皮功能的生化标记物。内皮微粒被发现可以推进细胞生存、发挥抗炎效应、抗凝血过程、诱导内皮再生,因此内皮微粒是有害的观点受到挑战。这被称为内皮微粒在血管动态平衡中的矛盾作用。     

Endothelial dysfunction in hypertension

Endothelial cells release both relaxing and contracting factors that modulate vascular smooth muscle tone and also participate in the pathophysiology of essential hypertension. Endothelium-dependent vasodilation is regulated primarily by nitric oxide but also by an unidentified endothelium-derived hyperpolarizing factor and by prostacyclin. Endothelium-derived contracting factors include endothelin-1, vasoconscrictor prostanoids, angiotensin II and superoxide anions. Under physiological conditions, there is a balanced release of relaxing and contracting factors. The balance can be altered in cardiovascular diseases such as hypertension, atherosclerosis, diabetes and other conditions, thereby contributing to further progression of vascular and end-organ damage. In particular, endothelial dysfunction leading to decreased bioavailability of nitric oxide impairs endothelium-dependent vasodilation in patients with essential hypertension and may also be a determinant for the premature development of atherosclerosis. Different mechanisms of reduced nitric oxide activity have been shown both in hypertensive states and several cardiovascular diseases, and endothelial dysfunction is likely to occur prior to vascular dysfunction. Thus, the strategies currently used to improve endothelial dysfunction may result in decreased morbidity and mortality in hypertensive patients.     

Endothelial function and hypertension

PURPOSE OF REVIEW: Endothelial dysfunction, in particular a reduced vascular availability of endothelium-derived nitric oxide, has been analysed in numerous experimental and clinical studies as a potential mechanism mediating the adverse vascular effects of hypertension. This paper outlines some notable studies in this dynamic field published recently. RECENT FINDINGS: The understanding of mechanisms underlying endothelial dysfunction in hypertension has been substantially advanced recently. Increased oxidant stress is thought to represent a major mechanism leading to reduced vascular availability of endothelium-derived nitric oxide. Vascular nicotinamide adenine dinucleotide phosphate oxidases, uncoupled nitric oxide synthase and xanthine oxidase have been identified as major sources of reactive oxygen species in hypertension. Endothelial dysfunction has been implicated in the macrovascular complications of hypertension, such as stroke or myocardial infarction, coronary microvascular dysfunction and increased arterial stiffness, probably at least partly resulting from loss of the antiatherogenic and vasculoprotective effects of endothelium-derived nitric oxide. SUMMARY: Recent research on endothelial dysfunction supports its clinical significance in hypertension, and has led to important insights into the pathophysiology of the disease. These observations suggest that targeting endothelial dysfunction, in particular reduced nitric oxide availability, would exert beneficial effects in hypertensive patients. This concept needs further evaluation in clinical studies.     

内皮源性一氧化氮合酶的活性调节

内皮源性一氧化氮合酶(eNOS)代谢精氨酸产生的一氧化氮(NO)在调节血管的稳态中发挥着重要作用,内皮功能失调所致疾病多与NO的释放和活性受损有关。近年来关于eNOS活性词节的研究很多,机制主要包括乙酰化修饰所决定的亚细胞定位,蛋白-蛋白相互作用以及磷酸化修饰。许多体液因子和机械刺激可通过不同的方式调节eNOS活性。为了更好地认识eNOS的活性调节,本文就该领域最新的研究进展进行归纳总结。