Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States of America.
PLoS One. 2012;7(12):e51483. doi: 10.1371/journal.pone.0051483. Epub 2012 Dec 7.
Whole body genetic deletion of AT1a receptors in mice uniformly reduces hypercholesterolemia and angiotensin II-(AngII) induced atherosclerosis and abdominal aortic aneurysms (AAAs). However, the role of AT1a receptor stimulation of principal cell types resident in the arterial wall remains undefined. Therefore, the aim of this study was to determine whether deletion of AT1a receptors in either endothelial cells or smooth muscle cells influences the development of atherosclerosis and AAAs.
METHODOLOGY/PRINCIPAL FINDINGS: AT1a receptor floxed mice were developed in an LDL receptor -/- background. To generate endothelial or smooth muscle cell specific deficiency, AT1a receptor floxed mice were bred with mice expressing Cre under the control of either Tie2 or SM22, respectively. Groups of males and females were fed a saturated fat-enriched diet for 3 months to determine effects on atherosclerosis. Deletion of AT1a receptors in either endothelial or smooth muscle cells had no discernible effect on the size of atherosclerotic lesions. We also determined the effect of cell-specific AT1a receptor deficiency on atherosclerosis and AAAs using male mice fed a saturated fat-enriched diet and infused with AngII (1,000 ng/kg/min). Again, deletion of AT1a receptors in either endothelial or smooth muscle cells had no discernible effects on either AngII-induced atherosclerotic lesions or AAAs.
Although previous studies have demonstrated whole body AT1a receptor deficiency diminishes atherosclerosis and AAAs, depletion of AT1a receptors in either endothelial or smooth muscle cells did not affect either of these vascular pathologies.
在小鼠中全身敲除 AT1a 受体可均匀降低高胆固醇血症和血管紧张素 II（AngII）诱导的动脉粥样硬化和腹主动脉瘤（AAA）。然而，AT1a 受体刺激动脉壁固有细胞类型的作用仍未确定。因此，本研究旨在确定内皮细胞或平滑肌细胞中 AT1a 受体的缺失是否会影响动脉粥样硬化和 AAA 的发展。
方法/主要发现：在 LDL 受体-/-背景下开发了 AT1a 受体 floxed 小鼠。为了产生内皮细胞或平滑肌细胞特异性缺乏，将 AT1a 受体 floxed 小鼠与分别在 Tie2 或 SM22 控制下表达 Cre 的小鼠杂交。雄性和雌性的小鼠被喂食富含饱和脂肪的饮食 3 个月，以确定其对动脉粥样硬化的影响。内皮细胞或平滑肌细胞中 AT1a 受体的缺失对动脉粥样硬化病变的大小没有明显影响。我们还使用雄性小鼠进行了实验，它们被喂食富含饱和脂肪的饮食并输注 AngII（1000ng/kg/min），以确定细胞特异性 AT1a 受体缺失对动脉粥样硬化和 AAA 的影响。同样，内皮细胞或平滑肌细胞中 AT1a 受体的缺失对 AngII 诱导的动脉粥样硬化病变或 AAA 均无明显影响。
尽管先前的研究表明全身 AT1a 受体缺失可减少动脉粥样硬化和 AAA，但内皮细胞或平滑肌细胞中 AT1a 受体的耗竭均不会影响这两种血管病变。
