DIETARY FATTY ACID MODULATION OF MYOCARDIAL FUNCTION AND INFLUENCES ON AGING

膳食脂肪酸对心肌功能的调节及其对衰老的影响

• 批准号: 3745550
• 负责人: S PEPE
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3745550
• 关键词: action potentials; adenosinetriphosphatase; aging; animal old age; arrhythmia; calcium channel blockers; calcium flux; dietary lipid; enzyme activity; heart cell; heart function; homeostasis; hypoxia; immature animal; isoproterenol; laboratory rat; membrane lipids; myocardium; nutrition of aging; nutrition related tag; oxygen consumption; sarcoplasmic reticulum; unsaturated fatty acids; vasodilation

This laboratory has shown that cardiac myocyte contraction time, its action potential and cytosolic Ca++ transient are extended with increasing age in rats. In addition, with increased age the threshold for Ca2+ overload of ra cardiac cells is reduced. Age-related changes in cardiac function and increased vulnerability to arrhythmogenic stimuli may be associated with alterations to membrane composition which may be intervened by dietary lipi modification of myocardial cell membranes. In this project we demonstrated following 8 weeks feeding of a basic reference diet to Wistar rats the proportion of ventricular membrane arachidonic acid (AA; n-6 polyunsaturate fatty acid, PUFA) increased and docosahexaenoic acid (DHA; n-3 PUFA) decreased in 24mo rats compared to 6mo rats. Treatment with a diet rich in saturated fat (SAT) distinctly augmented this age effect whereas FO prevented the age-related decrease in the n-3/n-6 PUFA ratio. An experimental protocol was employed which stresses cell membrane ion homeostasis related to membrane function. When stimulated at 2 Hz contraction amplitudes decreased in all groups, while SAT myocytes had the smallest contraction amplitude, FO myocytes were relatively resistant to this effect. When 0.5 or 2Hz stimulation was ceased no difference in the number of "spontaneous" cell contractions or "waves" (indicative of intracellular Ca2+ rising above the threshold for Ca2+ induced Ca2+ release and causing a spontaneous Ca2+ release from SR and thus potentially spontaneous contractions). However, the time to the first spontaneous wave was significantly longer for FO myocytes. Isoproterenol or BAYK8644 increased the number of waves and decreased the time to their onset. SAT diet markedly augmented this but FO diet provided protection by attenuating the severity of these effects. Thus results indicate that SAT diet exacerbates, and FO diet provides resistance against, age associated cardia cell Ca2+ tolerance and arrythmogenic triggers. These effects may be due to changes in cell membrane lipid composition.

本实验室已证明，心肌细胞收缩时间，其作用 电位和胞浆Ca++瞬变随着年龄的增长而延长， 大鼠此外，随着年龄的增加，RA细胞Ca ~（2+）超载的阈值降低， 心肌细胞减少。心脏功能的变化， 对致瘤性刺激的脆弱性增加可能与 膳食脂肪可能会干预膜组成的改变 修饰心肌细胞膜。在这个项目中，我们展示了 在对Wistar大鼠喂食基础参考饮食8周后， 心室膜花生四烯酸（AA）比例 脂肪酸（PUFA）增加和二十二碳六烯酸（DHA; n-3 PUFA） 与6个月大鼠相比，24个月大鼠中降低。饮食治疗富含 饱和脂肪（SAT）明显增强了这种年龄效应，而FO 防止n-3/n-6 PUFA比率的年龄相关性降低。一个 采用了一种实验方案，其对细胞膜离子施加应力， 与膜功能有关的稳态。当以2 Hz刺激时 收缩幅度在所有组中均降低，而SAT肌细胞具有 最小的收缩幅度，FO肌细胞相对抵抗 这种效果。当停止0.5或2 Hz刺激时， “自发”细胞收缩或“波”的数量（指示 细胞内Ca 2+升高到Ca 2+诱导的Ca 2+释放的阈值以上 并导致SR自发释放Ca 2+， 自发性收缩）。然而，第一个自发波的时间 FO肌细胞的时间显著延长。异丙肾上腺素或BAYK 8644 增加了波的数量，缩短了波的开始时间。坐 饮食明显增强了这一点，但FO饮食通过减弱 这些影响的严重性。因此，结果表明， 加重，FO饮食提供抵抗，年龄相关的贲门 细胞Ca 2+耐受和心律失常触发因素。这些影响可能是由于 细胞膜脂质组成的变化。