Cardiovascular Pharmacology Division, Department of Pharmacology, Institute of Pharmacy, Rajendra Institute of Technology and Sciences (RITS), Sirsa, India.
Cell Signal. 2012 Mar;24(3):589-95. doi: 10.1016/j.cellsig.2011.11.003. Epub 2011 Nov 9.
Ischemic heart disease is a leading cause of death worldwide. Myocardial ischemia results in reduced coronary flow, followed by diminished oxygen and nutrient supply to the heart. Reperfusion to an ischemic myocardium often augments the ischemic damage, known as ischemia-reperfusion (I/R) injury. Number of studies demonstrated that the hyperlipidemic myocardium is rather sensitive and more vulnerable to I/R-induced myocardial injury. Repeated brief ischemia and reperfusion cycles, termed as ischemic preconditioning, given before a sustained ischemia is known to reduce myocardial damage occur as a result of I/R. A plethora of evidence supports the fact that preconditioning is one of the promising interventional strategies having an ability to limit I/R-induced myocardial injury. Despite this fact, the preconditioning-mediated cardioprotection is blunted in chronic hyperlipidemic condition. This suggests that preconditioning is moderately a 'healthy heart protective phenomenon'. The mechanisms by which chronic hyperlipidemia abrogates cardioprotective effects of preconditioning are uncertain and are not completely understood. The impaired opening of mitochondrial-K(ATP) channels, eNOS uncoupling and excessive generation of superoxides in the hyperlipidemic myocardium could play a role in attenuating preconditioning-mediated myocardial protection against I/R injury. Moreover, hyperlipidemia-induced loss of cardioprotective effect of preconditioning is associated with redistribution of both sarcolemmal and mitochondrial Connexin 43. We addressed, in this review, the potential mechanisms involved in hyperlipidemia-induced impairment of myocardial preconditioning. Additionally, novel pharmacologic interventions to attenuate hyperlipidemia-associated exaggerated I/R-induced myocardial injury have been discussed.
缺血性心脏病是全球范围内主要的死亡原因。心肌缺血导致冠状动脉血流减少，随后心脏的氧气和营养供应减少。缺血心肌的再灌注常常会加剧缺血损伤，即缺血再灌注（I/R）损伤。大量研究表明，高脂血症心肌对 I/R 诱导的心肌损伤相当敏感和脆弱。在持续缺血之前给予的反复短暂缺血和再灌注循环，称为缺血预处理，已知可以减少由于 I/R 引起的心肌损伤。大量证据支持这样一个事实，即预处理是一种有能力限制 I/R 诱导的心肌损伤的有前途的干预策略之一。尽管如此，在慢性高脂血症条件下，预处理介导的心脏保护作用会减弱。这表明预处理是一种“健康心脏保护现象”。慢性高脂血症消除预处理的心脏保护作用的机制尚不确定，也不完全清楚。在高脂血症心肌中，线粒体 K(ATP)通道的开放受损、eNOS 解偶联和超氧化物的过度产生可能在减弱预处理介导的对 I/R 损伤的心肌保护作用中发挥作用。此外，高脂血症引起的预处理对心脏保护作用的丧失与肌膜和线粒体 Connexin 43 的重新分布有关。在这篇综述中，我们讨论了参与高脂血症诱导的心肌预处理损伤的潜在机制。此外，还讨论了减轻与高脂血症相关的过度 I/R 诱导的心肌损伤的新型药物干预措施。
