Is angiotensin II receptor activation involved in the mechanism and pathophysiological role of oxidized LDL?

在这项研究中，我们调查了我们的假设，即血管紧张素II 1型受体(AT1)参与了氧化型低密度脂蛋白(OxLDL)诱导的血管反应，参与了心血管疾病的发病机制。我们发现，oxLDL激活细胞信号的能力需要凝集素样oxLDL受体(LOX-1)和AT1，LOX-1和AT1在细胞表膜上形成受体复合体。AT1基因突变大大降低了oxLDL激活G蛋白和MAP激酶的能力。此外，oxLDL诱导的小鼠急性血压升高，这些高血压效应可通过AT1a或LOX-1的缺失完全消除。此外，在小鼠中，通过ARB或AT1基因缺失，oxLDL诱导的内皮依赖性血管松弛的损伤被消除。这些发现表明，oxLDL诱导的AT1激活构成了一种迄今尚不清楚的机制，可能进一步有助于oxLDL对动脉粥样硬化风险的影响。

In this study, we investigated our hypothesis that the angiotensin II type 1 receptor (AT1) is involved in the oxidized LDL (oxLDL)-induced vascular responses involved in the pathogenesis of cardiovascular disease. We found that both the lectin like oxLDL receptor (LOX-1) and AT1 are required for the ability of oxLDL to activate cell signaling and that LOX-1 and AT1 form receptor complexes on cell surface membranes. Mutations in AT1 greatly reduced the capacity of oxLDL to activate G protein and MAP kinase. In addition, oxLDL induced acute blood pressure elevations in mice and these hypertensive effects were totally abolished by deletion of AT1a or LOX-1. In addition, oxLDL-induced impairment of endothelial-dependent vascular relaxation was abolished by ARB or genetic deletion of AT1 in mice. These findings indicate that oxLDL-induced activation of AT1 constitutes a heretofore unrecognized mechanism that could further contribute to the effects of oxLDL on risk for atherosclerosis.