Sparagna Genevieve C, Chicco Adam J, Murphy Robert C, Bristow Michael R, Johnson Christopher A, Rees Meredith L, Maxey Melissa L, McCune Sylvia A, Moore Russell L
Department of Integrative Physiology, University of Colorado Cardiovascular Institute, University of Colorado at Boulder, Boulder, CO 80309-0354, USA.
J Lipid Res. 2007 Jul;48(7):1559-70. doi: 10.1194/jlr.M600551-JLR200. Epub 2007 Apr 10.
The mitochondrial phospholipid cardiolipin is required for optimal mitochondrial respiration. In this study, cardiolipin molecular species and cytochrome oxidase (COx) activity were studied in interfibrillar (IF) and subsarcolemmal (SSL) cardiac mitochondria from Spontaneously Hypertensive Heart Failure (SHHF) and Sprague-Dawley (SD) rats throughout their natural life span. Fisher Brown Norway (FBN) and young aortic-constricted SHHF rats were also studied to investigate cardiolipin alterations in aging versus pathology. Additionally, cardiolipin was analyzed in human hearts explanted from patients with dilated cardiomyopathy. A loss of tetralinoleoyl cardiolipin (L(4)CL), the predominant species in the healthy mammalian heart, occurred during the natural or accelerated development of heart failure in SHHF rats and humans. L(4)CL decreases correlated with reduced COx activity (no decrease in protein levels) in SHHF cardiac mitochondria, but with no change in citrate synthase (a matrix enzyme) activity. The fraction of cardiac cardiolipin containing L(4)CL became much lower with age in SHHF than in SD or FBN mitochondria. In summary, a progressive loss of cardiac L(4)CL, possibly attributable to decreased remodeling, occurs in response to chronic cardiac overload, but not aging alone, in both IF and SSL mitochondria. This may contribute to mitochondrial respiratory dysfunction during the pathogenesis of heart failure.
最佳线粒体呼吸需要线粒体磷脂心磷脂。在本研究中，我们在整个自然寿命期间，对自发性高血压心力衰竭（SHHF）大鼠和斯普拉格-道利（SD）大鼠的肌原纤维间（IF）和肌膜下（SSL）心脏线粒体中的心磷脂分子种类和细胞色素氧化酶（COx）活性进行了研究。还对费希尔-布朗挪威（FBN）大鼠和年轻的主动脉缩窄SHHF大鼠进行了研究，以探讨衰老与病理状态下心磷脂的变化。此外，我们分析了扩张型心肌病患者心脏移植后的人心脏中的心磷脂。在SHHF大鼠和人类心力衰竭的自然或加速发展过程中，健康哺乳动物心脏中的主要心磷脂种类——四亚麻酰基心磷脂（L(4)CL）出现了丢失。L(4)CL的减少与SHHF心脏线粒体中COx活性的降低相关（蛋白质水平无下降），但柠檬酸合酶（一种基质酶）活性没有变化。与SD或FBN线粒体相比，SHHF线粒体中心脏心磷脂中含L(4)CL的比例随年龄增长下降得更多。总之，在IF和SSL线粒体中，慢性心脏超负荷而非单纯衰老会导致心脏L(4)CL逐渐丢失，这可能归因于重塑减少，这可能在心力衰竭发病机制中导致线粒体呼吸功能障碍。
