血管紧张素 II 型 1 型受体阻滞剂对临床前模型主动脉瓣硬化的影响。

Effects of an angiotensin II type 1 receptor blocker on aortic valve sclerosis in a preclinical model.

机构信息

Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.

Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Imaging Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.

出版信息

Can J Cardiol. 2014 Sep;30(9):1096-103. doi: 10.1016/j.cjca.2013.12.027. Epub 2014 Jan 3.

DOI:10.1016/j.cjca.2013.12.027

PMID:24726090

Abstract

BACKGROUND

Aortic valve sclerosis (AVS) is a chronic progressive disease involving lipid infiltration, inflammation, and tissue calcification. Despite its high prevalence, there are currently no clinically approved pharmaceuticals for the management of AVS. The objective of the current study was to elucidate the effects of an angiotensin II type 1 receptor blocker, alone or in combination with statin therapy, on the progression of AVS.

METHODS

Male New Zealand white rabbits were fed an atherogenic diet for a period of 12 months to induce AVS. Once disease was established, rabbits were randomly assigned to receive no treatment, olmesartan medoxomil, atorvastatin calcium, or a combination of both drugs for a period of 6 months. Disease progression was monitored in vivo using clinically relevant magnetic resonance imaging, and aortic valve cusps were examined ex vivo using histologic and immunohistochemical methods.

RESULTS

Cusp thickness significantly increased (0.58 ± 0.03 vs 0.39 ± 0.03 mm for cholesterol and control animals, respectively; P < 0.0001) and all classic hallmarks of disease progression-including lipid infiltration, inflammation, and tissue calcification-were observed after 12 months. Unfortunately, neither olmesartan medoxomil nor atorvastatin calcium were able to reverse or delay disease progression during the 6-month treatment period. However, several histologic changes were observed in the valvular microenvironment.

CONCLUSIONS

The current study suggests that angiotensin receptor blockers, alone or in combination with statin therapy, may not be suitable for management of clinical AVS.

摘要

背景

主动脉瓣硬化（AVS）是一种慢性进行性疾病，涉及脂质浸润、炎症和组织钙化。尽管其患病率很高，但目前尚无临床批准的药物可用于治疗 AVS。本研究的目的是阐明血管紧张素 II 型 1 型受体阻滞剂单独或联合他汀类药物治疗对 AVS 进展的影响。

方法

雄性新西兰白兔给予致动脉粥样硬化饮食 12 个月以诱导 AVS。一旦疾病确立，兔子被随机分为不治疗、奥美沙坦酯、阿托伐他汀钙或两者联合治疗 6 个月。使用临床相关磁共振成像在体内监测疾病进展，并使用组织学和免疫组织化学方法在体外检查主动脉瓣瓣叶。

结果

瓣叶厚度显著增加（胆固醇和对照组动物分别为 0.58 ± 0.03 毫米和 0.39 ± 0.03 毫米；P < 0.0001），并且在 12 个月后观察到所有经典疾病进展标志-包括脂质浸润、炎症和组织钙化。不幸的是，奥美沙坦酯和阿托伐他汀钙在 6 个月的治疗期间均不能逆转或延缓疾病进展。然而，在瓣膜微环境中观察到了一些组织学变化。