Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases.
Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases.
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发表时间：
2000-03
影响因子：
21.1
通讯作者：
Shokei Kim;H. Iwao
中科院分区：
文献类型：
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作者：
Shokei Kim;H. Iwao
越来越多的证据支持这样一种观点：肾素 - 血管紧张素系统的核心产物血管紧张素II（Ang II）可能不仅在高血压的病因学中，而且在人类心血管和肾脏疾病的病理生理学中都起着核心作用。在这篇综述中，我们聚焦于Ang II在分子和细胞水平上在心血管和肾脏疾病中的作用，并讨论与血管紧张素转换酶抑制剂相比，有关Ang II的体外和体内作用以及血管紧张素受体拮抗剂的药理作用的最新证据。Ang II通过AT(1)受体直接导致细胞表型改变和细胞生长，调节各种生物活性物质（血管活性激素、生长因子、细胞外基质成分、细胞因子等）的基因表达，并激活心肌细胞和成纤维细胞、血管内皮细胞和平滑肌细胞以及肾系膜细胞中的多种细胞内信号级联反应（丝裂原活化蛋白激酶级联反应、酪氨酸激酶、各种转录因子等）。这些作用被认为参与了心肌肥大和重塑、心力衰竭、血管增厚、动脉粥样硬化和肾小球硬化的病理生理学过程。此外，体内近期的证据表明，Ang II对丝裂原活化蛋白激酶和激活蛋白 - 1的激活可能在心血管和肾脏疾病中起关键作用。然而，关于Ang II介导的心血管和肾脏疾病的机制仍然存在未解决的问题和争议。
A growing body of evidence supports the notion that angiotensin II (Ang II), the central product of the renin-angiotensin system, may play a central role not only in the etiology of hypertension but also in the pathophysiology of cardiovascular and renal diseases in humans. In this review, we focus on the role of Ang II in cardiovascular and renal diseases at the molecular and cellular levels and discuss up-to-date evidence concerning the in vitro and in vivo actions of Ang II and the pharmacological effects of angiotensin receptor antagonists in comparison with angiotensin-converting enzyme inhibitors. Ang II, via AT(1) receptor, directly causes cellular phenotypic changes and cell growth, regulates the gene expression of various bioactive substances (vasoactive hormones, growth factors, extracellular matrix components, cytokines, etc.), and activates multiple intracellular signaling cascades (mitogen-activated protein kinase cascades, tyrosine kinases, various transcription factors, etc.) in cardiac myocytes and fibroblasts, vascular endothelial and smooth muscle cells, and renal mesangial cells. These actions are supposed to participate in the pathophysiology of cardiac hypertrophy and remodeling, heart failure, vascular thickening, atherosclerosis, and glomerulosclerosis. Furthermore, in vivo recent evidence suggest that the activation of mitogen-activated protein kinases and activator protein-1 by Ang II may play the key role in cardiovascular and renal diseases. However, there are still unresolved questions and controversies on the mechanism of Ang II-mediated cardiovascular and renal diseases.