College of Clinical Medicine and Department of Pathology, Xi'an Medical University, Xi'an, China; Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, Japan.
Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, Japan.
Am J Pathol. 2018 Dec;188(12):2936-2947. doi: 10.1016/j.ajpath.2018.08.007. Epub 2018 Sep 21.
Hypertension is a major risk factor for the development of atherosclerosis. Cardiovascular risk has been reported to be significantly increased in hyperlipidemic patients with hypertension. However, it is not clear whether hypertension can directly destabilize plaques, thereby enhancing cardiovascular events. To examine whether hypertension enhances the development of atherosclerosis and increases plaque vulnerability, we generated hypertensive Watanabe heritable hyperlipidemic (WHHL) rabbits by surgical removal of one kidney and partial ligation of the other renal artery and compared the nature of aortic and coronary atherosclerosis in hypertensive WHHL rabbits with normotensive WHHL rabbits. All hypertensive WHHL rabbits died from 34 to 56 weeks after surgery, whereas no normotensive WHHL rabbits died. Pathologic examinations revealed that hypertensive WHHL rabbits showed different degrees of myocardial infarction caused by severe coronary stenosis along with myocardial hypertrophy. Furthermore, aortic lesions in hypertensive WHHL rabbits exhibited a higher frequency of intraplaque hemorrhage and vulnerable plaques than those in normotensive WHHL rabbits. These results indicate that hypertension induced by the surgical removal of one kidney and partial ligation of the other renal artery method in WHHL rabbits may not only enhance the development of atherosclerosis but also destabilize the plaques, increasing cardiac death.
高血压是动脉粥样硬化发展的主要危险因素。已有报道称，高血压合并高血脂患者的心血管风险显著增加。然而，目前尚不清楚高血压是否会直接使斑块不稳定，从而增加心血管事件的发生。为了研究高血压是否会促进动脉粥样硬化的发展并增加斑块易损性，我们通过手术切除一只肾脏并部分结扎另一只肾动脉的方法，在 Watanabe 遗传性高脂血症（WHHL）兔中诱发高血压，然后比较高血压 WHHL 兔和正常血压 WHHL 兔的主动脉和冠状动脉粥样硬化的性质。所有高血压 WHHL 兔均在手术后 34 至 56 周内死亡，而正常血压 WHHL 兔无一死亡。病理检查显示，高血压 WHHL 兔由于严重的冠状动脉狭窄导致心肌梗死，同时伴有心肌肥厚。此外，与正常血压 WHHL 兔相比，高血压 WHHL 兔的主动脉病变中斑块内出血和易损斑块的发生率更高。这些结果表明，通过手术切除一只肾脏并部分结扎另一只肾动脉的方法在 WHHL 兔中诱发的高血压不仅可以促进动脉粥样硬化的发展，还可以使斑块不稳定，增加心脏性死亡。
