Skultetyova Dana, Filipova Slavomira, Riecansky Igor, Skultety Jan
Department Cardiology, National Institute of Cardiovascular Diseases, Bratislava, Slovak Republic.
Recent Pat Cardiovasc Drug Discov. 2007 Jan;2(1):23-7. doi: 10.2174/157489007779606130.
Endothelial dysfunction plays an important role in all stages of atherosclerosis, and is characterized by an increased activity of vasoconstricting factors, proinflammatory and prothrombotic mediators. The aim of the review is to evaluate the role of angiotensin II (Ang II) and especially of angiotensin type 1 (AT1) receptor in inflammation and endothelial dysfunction. Ang II with AT(1) receptor are through several mechanisms implicated in the progression of atherosclerosis. Stimulation of AT(1) receptor increases oxidative stress especially through activation of NADH/NADPH oxidase in the vascular cells. Oxidative stress is associated with activation of the inflammatory processes. Ang II via AT(1) receptor increases expression of adhesion molecules and stimulates the induction of monocyte chemoattractant protein-1 (MCP-1). AT(1) receptor enhances the activation of nuclear factor NF-kappaB, which stimulates the production of proinflammatory cytokines. Proinflammatory cytokines on the other side may induce acute-phase response in the liver. Activation of AT(1) receptor via inducible cyclooxygenase (COX)-2 promotes biosynthesis of matrix metalloproteinases (MMPs). Ang II is implicated in the process of angiogenesis. Via AT(1) receptor takes part in the regulation of vascular endothelial growth factor (VEGF), which is one of the most angiogenic factors and stimulates the activity of endothelial progenitor cells (EPC). Recently some patents were reported discussing role of different compounds for the treatment of cardiovascular disease, renovascular disease nephropathy, peripheral vascular disease, portal hypertension and ophthalmic disorders, are cyclooxygenase-2 inhibitors.
内皮功能障碍在动脉粥样硬化的各个阶段都起着重要作用，其特征是血管收缩因子、促炎和促血栓形成介质的活性增加。本综述的目的是评估血管紧张素II（Ang II）尤其是1型血管紧张素（AT1）受体在炎症和内皮功能障碍中的作用。Ang II与AT1受体通过多种机制参与动脉粥样硬化的进展。刺激AT1受体可增加氧化应激，尤其是通过激活血管细胞中的NADH/NADPH氧化酶。氧化应激与炎症过程的激活有关。Ang II通过AT1受体增加黏附分子的表达，并刺激单核细胞趋化蛋白-1（MCP-1）的诱导。AT1受体增强核因子NF-κB的激活，后者刺激促炎细胞因子的产生。另一方面，促炎细胞因子可能诱导肝脏中的急性期反应。通过诱导型环氧化酶（COX）-2激活AT1受体可促进基质金属蛋白酶（MMP）的生物合成。Ang II参与血管生成过程。通过AT1受体参与血管内皮生长因子（VEGF）的调节，VEGF是最具血管生成作用的因子之一，可刺激内皮祖细胞（EPC）的活性。最近有一些专利报道了讨论不同化合物在治疗心血管疾病、肾血管疾病、肾病、外周血管疾病、门静脉高压和眼科疾病中的作用，这些化合物是环氧化酶-2抑制剂。
