Molecular Internal Medicine, University of Zurich, Zurich, Switzerland.
Br J Pharmacol. 2012 Feb;165(3):591-602. doi: 10.1111/j.1476-5381.2011.01472.x.
Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis-related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium-derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, 'premature' vascular aging. Here, we will review some of the pathomechanisms involved in obesity-related activation of endothelium-dependent vasoconstriction, the clinical relevance of obesity-associated vascular risk, and therapeutic interventions using 'endothelial therapy' aiming at maintaining or restoring vascular endothelial health.
This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3.
肥胖已成为影响成人和儿童的严重全球健康问题。世界人口统计学的最新发展和世界人口健康状况的下降表明,肥胖的流行率在未来几十年将继续增加。作为一种疾病,肥胖对代谢稳态有有害影响,并影响包括心脏、肾脏和血管系统在内的许多器官系统。因此,肥胖现在被认为是与动脉粥样硬化相关疾病(如冠心病、心肌梗死和中风)相关的独立风险因素。在动脉系统中,内皮细胞既是导致动脉粥样硬化的因素的来源,也是其作用靶点。内皮血管活性因子在生理条件下调节血管稳态,维持基础血管张力。肥胖导致内皮衍生的血管活性因子之间失衡,有利于血管收缩、细胞生长和炎症激活。由于内皮细胞功能障碍导致这些因子的调节异常,既是血管疾病过程的结果,也是其原因。最后,由于激活的血管病理机制相似,肥胖可被认为导致加速的、“过早的”血管老化。在这里,我们将回顾一些与肥胖相关的内皮依赖性血管收缩激活相关的病理机制、肥胖相关血管风险的临床相关性,以及旨在维持或恢复血管内皮健康的“内皮治疗”的治疗干预。
本文是关于脂肪和血管反应性的专题部分的一部分。要查看本节中的其他文章,请访问 http://dx.doi.org/10.1111/bph.2012.165.issue-3.