Toro Ligia, Marijic Jure, Nishimaru Kazuhide, Tanaka Yoshio, Song Min, Stefani Enrico
Department of Anesthesiology, Department of Molecular and Medical Pharmacology, Brain Research Institute, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1778, USA.
Vascul Pharmacol. 2002 Jan;38(1):73-80. doi: 10.1016/s0306-3623(02)00128-3.
Cardiovascular disease remains the leading cause of death in the United States, and aging is one of the main risk factors for its development. Coronary arteries nurture the heart, but as age progresses, they suffer changes that make them stiffer, thicker, and with higher spontaneous contractile activity. Even in the absence of pathological atherosclerotic lesions, these changes make the coronary arteries at risk for vasospasm and the individual at risk for myocardial ischemia and heart failure. Thus, knowledge of the molecular mechanisms involved in the vascular physiology, disease, and aging of the coronary circulation is required to develop strategies to preserve the quality of life of an increasingly aging population. One of the key factors that regulate coronary arterial tone is the activity of K+ channels in the vascular smooth muscle cells (SMCs). In particular, voltage-dependent and Ca(2+)-activated K+ (BKCa) channels, which are abundant in the coronary SMCs, are targets of vasoconstrictors and vasorelaxants, and play a key role in determining arterial tone and diameter. Aging induces a reduction in the density of the alpha-subunit of BKCa channels in coronary smooth muscle, lowers baseline endothelial release of the relaxant nitric oxide (NO), and increases the response to endothelial constrictor factors and K+. Thus, aging induces the remodeling of important proteins involved in the excitability and contractility of the coronary circulation. Altogether, these changes increase the risk of coronary artery vasospasm, myocardial ischemia, and infarct in the elderly.
心血管疾病仍然是美国的主要死因，而衰老则是其发展的主要风险因素之一。冠状动脉滋养心脏，但随着年龄的增长，它们会发生变化，变得更硬、更厚，且自发收缩活动增强。即使没有病理性动脉粥样硬化病变，这些变化也会使冠状动脉有发生血管痉挛的风险，使个体有发生心肌缺血和心力衰竭的风险。因此，要制定策略来维持日益老龄化人口的生活质量，就需要了解参与冠状动脉循环的血管生理学、疾病和衰老过程的分子机制。调节冠状动脉张力的关键因素之一是血管平滑肌细胞（SMC）中钾通道的活性。特别是，电压依赖性和钙激活钾（BKCa）通道在冠状动脉SMC中大量存在，它们是血管收缩剂和血管舒张剂的作用靶点，在决定动脉张力和直径方面起关键作用。衰老会导致冠状动脉平滑肌中BKCa通道α亚基的密度降低，降低舒张性一氧化氮（NO）的基线内皮释放，并增加对内皮收缩因子和钾的反应。因此，衰老会导致参与冠状动脉循环兴奋性和收缩性的重要蛋白质发生重塑。总之，这些变化增加了老年人冠状动脉血管痉挛、心肌缺血和梗死的风险。
