Angiotensin II Destabilizes Coronary Plaques in Watanabe Heritable Hyperlipidemic Rabbits.
Angiotensin II Destabilizes Coronary Plaques in Watanabe Heritable Hyperlipidemic Rabbits.
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DOI：
10.1161/atvbaha.115.306871
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Fan J
中科院分区：
文献类型：
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作者：
Li S;Wang YN;Niimi M;Ning B;Chen Y;Kang D;Wang Z;Yu Q;Waqar AB;Liu E;Zhang J;Shiomi M;Chen YE;Fan J
血管紧张素II（angiotensin II，Ang II）的血浆浓度升高与许多心血管疾病如动脉粥样硬化、主动脉瘤和心肌梗死有关。然而，尚不清楚高水平的血浆血管紧张素II是否影响冠状动脉斑块的稳定性和随后的心肌梗死。本研究旨在探讨血浆血管紧张素II升高是否能直接诱发冠状动脉事件，如急性冠状动脉综合征。为了验证上述假设，我们通过渗透性微型泵将Ang II [100 ng/min/kg（低组）和200 ng/min/kg（高组）]或生理盐水载体输注到WHHL家兔（一种人类家族性高胆固醇血症和动脉粥样硬化模型）中。输注血管紧张素II导致低和高血管紧张素II组的死亡率分别为50%和92%，而溶媒组没有死亡。病理分析显示，Ang II灌注的WHHL家兔死亡后出现心肌梗死。此外，血管紧张素II灌注的WHHL兔表现出冠状动脉斑块侵蚀和破裂与血栓形成。这些结果表明，血管紧张素II的血液水平的增加，可以不稳定的冠状动脉斑块和触发血栓形成，这可能会导致心肌梗死。该模型为研究急性冠脉综合征提供了一种新的手段。
Increased plasma concentrations of angiotensin II (Ang II) have been implicated in many cardiovascular diseases such as atherosclerosis, aortic aneurysms and myocardial infarction in humans. However, it is not known whether high levels of plasma Ang II affect coronary plaque stability and subsequent myocardial infarction. The current study was designed to examine whether elevated plasma Ang II can directly induce coronary events such as acute coronary syndrome. To examine the above hypothesis, we infused Ang II [100 ng/min/kg (low group) and 200 ng/min/kg (high group)] or saline vehicle via osmotic minipumps into WHHL rabbits, a model of human familial hypercholesterolemia and atherosclerosis. Infusion of Ang II resulted in mortality rates of 50% and 92% in the low- and high-Ang II groups, respectively, while there were no deaths in the vehicle group. Pathological analysis revealed that Ang II-infused WHHL rabbits that died showed myocardial infarction. Furthermore, Ang II-infused WHHL rabbits exhibited coronary plaque erosion and rupture that were associated with thrombosis. These findings suggest that increased blood levels of Ang II can destabilize coronary plaques and trigger the thrombosis, which possibly induces myocardial infarction. The model described in this study provides a novel means for the study of human acute coronary syndrome.