Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Toxicol Mech Methods. 2012 Jun;22(5):359-66. doi: 10.3109/15376516.2012.666650. Epub 2012 Mar 20.
Cardiac hypertrophy (CH) is an adaptive response of the heart to pressure overload. It is a common pathological feature in the natural course of some major cardiovascular diseases, like, hypertension and myocardial infarction. Cardiac hypertrophy is strongly associated with an increased risk of heart failure and sudden cardiac death. The complex and dynamic pathophysiological mechanisms of CH has been the focus of intense scientific investigation, in an effort to design preventive and curative strategies. Oxidative stress has been identified as one of the key contributing factors in the development of cardiac hypertrophy. In this review, evidences supporting the oxidative stress as a cause of cardiac hypertrophy with emphasis on mitochondrial oxidative stress and possible options for pharmacological interventions have been discussed. Reactive oxygen species (ROS) also activate a broad variety of hypertrophy signaling kinases and transcription factors, like, MAP kinase, NF K-B, etc. In addition to profound alteration of cellular function, ROS modulate the extracellular matrix function, evidenced by increased interstitial and perivascular fibrosis. Translocator protein (TSPO) present in the outer mitochondrial membrane is known to be involved in oxidative stress and cardiovascular pathology. Recently, its role in cardiac hypertrophy has been reported by us. All these evidences strongly provide support to beneficial role of drugs which selectively interfere with the generation of free radicals or augment endogenous antioxidants in cardiac hypertrophy.
心肌肥厚(CH)是心脏对压力超负荷的适应性反应。它是一些主要心血管疾病(如高血压和心肌梗死)自然病程中的常见病理特征。心肌肥厚与心力衰竭和心源性猝死的风险增加密切相关。CH 的复杂和动态病理生理机制一直是科学研究的重点,旨在设计预防和治疗策略。氧化应激已被确定为心肌肥厚发展的关键因素之一。在这篇综述中,讨论了支持氧化应激作为心肌肥厚原因的证据,重点是线粒体氧化应激和可能的药物干预选择。活性氧(ROS)还激活了多种肥大信号激酶和转录因子,如 MAP 激酶、NF K-B 等。除了细胞功能的深刻改变外,ROS 还调节细胞外基质功能,表现为间质和血管周围纤维化增加。位于线粒体外膜的转位蛋白(TSPO)已知参与氧化应激和心血管病理学。最近,我们报道了其在心肌肥厚中的作用。所有这些证据都强烈支持选择性干扰自由基生成或增强内源性抗氧化剂在心肌肥厚中的作用的药物的有益作用。