Aroor Annayya R, Demarco Vincent G, Jia Guanghong, Sun Zhe, Nistala Ravi, Meininger Gerald A, Sowers James R
Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Missouri Columbia School of Medicine , Columbia, MO , USA ; Harry S. Truman Memorial Veterans Hospital , Columbia, MO , USA.
Front Endocrinol (Lausanne). 2013 Oct 29;4:161. doi: 10.3389/fendo.2013.00161.
Epidemiological studies support the notion that arterial stiffness is an independent predictor of adverse cardiovascular events contributing significantly to systolic hypertension, impaired ventricular-arterial coupling and diastolic dysfunction, impairment in myocardial oxygen supply and demand, and progression of kidney disease. Although arterial stiffness is associated with aging, it is accelerated in the presence of obesity and diabetes. The prevalence of arterial stiffness parallels the increase of obesity that is occurring in epidemic proportions and is partly driven by a sedentary life style and consumption of a high fructose, high salt, and high fat western diet. Although the underlying mechanisms and mediators of arterial stiffness are not well understood, accumulating evidence supports the role of insulin resistance and endothelial dysfunction. The local tissue renin-angiotensin-aldosterone system (RAAS) in the vascular tissue and immune cells and perivascular adipose tissue is recognized as an important element involved in endothelial dysfunction which contributes significantly to arterial stiffness. Activation of vascular RAAS is seen in humans and animal models of obesity and diabetes, and associated with enhanced oxidative stress and inflammation in the vascular tissue. The cross talk between angiotensin and aldosterone underscores the importance of mineralocorticoid receptors in modulation of insulin resistance, decreased bioavailability of nitric oxide, endothelial dysfunction, and arterial stiffness. In addition, both innate and adaptive immunity are involved in this local tissue activation of RAAS. In this review we will attempt to present a unifying mechanism of how environmental and immunological factors are involved in this local tissue RAAS activation, and the role of this process in the development of endothelial dysfunction and arterial stiffness and targeting tissue RAAS activation.
流行病学研究支持这样一种观点，即动脉僵硬度是不良心血管事件的独立预测因子，对收缩期高血压、心室 - 动脉耦联受损和舒张功能障碍、心肌氧供需受损以及肾脏疾病进展有显著影响。尽管动脉僵硬度与衰老相关，但在肥胖和糖尿病存在时会加速。动脉僵硬度的患病率与肥胖的增加同步，肥胖正以流行比例出现，部分是由久坐的生活方式以及高果糖、高盐和高脂肪的西方饮食消费所驱动。尽管动脉僵硬度的潜在机制和介质尚未完全了解，但越来越多的证据支持胰岛素抵抗和内皮功能障碍的作用。血管组织、免疫细胞和血管周围脂肪组织中的局部组织肾素 - 血管紧张素 - 醛固酮系统（RAAS）被认为是参与内皮功能障碍的一个重要因素，而内皮功能障碍对动脉僵硬度有显著影响。在肥胖和糖尿病的人类及动物模型中可见血管RAAS的激活，并与血管组织中氧化应激和炎症增强相关。血管紧张素和醛固酮之间的相互作用强调了盐皮质激素受体在调节胰岛素抵抗、一氧化氮生物利用度降低、内皮功能障碍和动脉僵硬度方面的重要性。此外，先天免疫和适应性免疫都参与了这种局部组织RAAS的激活。在这篇综述中，我们将试图提出一个统一的机制，说明环境和免疫因素如何参与这种局部组织RAAS的激活，以及这个过程在内皮功能障碍和动脉僵硬度发展中的作用，并针对组织RAAS激活进行研究。
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