Obesity Induces Signs of Premature Cardiac Aging in Younger Patients The Role of Mitochondria
Obesity Induces Signs of Premature Cardiac Aging in Younger Patients The Role of Mitochondria
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DOI：
10.1016/j.jacc.2010.09.040
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发表时间：
2011-02-01
影响因子：
24
通讯作者：
Rohrbach, Susanne
中科院分区：
文献类型：
--
作者：
Niemann, Bernd;Chen, Ying;Rohrbach, Susanne
目的探讨肥胖对心脏老化的影响。背景肥胖与左心室肥厚、舒张期功能障碍、心力衰竭和动脉粥样硬化的发生率增加有关。方法60例男性心脏手术患者，按体重指数(18.5~25 kg/m(2)：正常体重；30~35 kg/m(2)：肥胖)和(70岁：70岁)分为4组，每组15例。分析右心房心肌细胞线粒体功能、细胞凋亡标志物、心脏负荷或代谢以及氧化应激参数。结果肥胖导致青年和老年患者心肌细胞线粒体生物发生和功能紊乱(呼吸链复合体I)。线粒体功能紊乱与氧化应激(蛋白质羰基含量，8-羟基-2‘-脱氧鸟苷)以及端粒缩短高达30%的迹象有关。老年(肥胖和正常体重)和年轻肥胖患者的心肌细胞表现出较高的负荷诱导标志物(心钠素和脑利钠肽)水平和促凋亡活性，Bax和Bclxs表达增加，细胞色素C释放和caspase3/9激活。在老年(肥胖和正常体重)和年轻肥胖患者中均可检测到糖代谢和脂肪细胞因子释放的紊乱。然而，在70岁以上的肥胖者中，与年龄匹配的正常体重的患者相比，大多数参数只有轻微的恶化。结论这些数据表明肥胖导致较年轻患者的心脏过早老化，这可能是心力衰竭风险增加的原因之一。(J Am Coll心脏ol 2011；57：577-85)(C)2011，美国心脏病学会基金会
Objectives The purpose of the present study was to investigate the influence of obesity on cardiac aging.Background Obesity is associated with an increased incidence of left ventricular hypertrophy, diastolic dysfunction, heart failure, and atherosclerosis.Methods Sixty male cardiac surgery patients were included in the study according to body mass index (18.5 to 25 kg/m(2): normal weight; 30 to 35 kg/m(2): obese) and age (70 years: old) and divided into 4 groups of 15 patients each. Right atrial cardiomyocytes were analyzed for mitochondrial function, markers of apoptosis, cardiac load or metabolism, and oxidative stress parameters. The metabolic state was further characterized in fasting blood samples.Results Obesity resulted in disturbed mitochondrial biogenesis and function (respiratory chain complex I) in the cardiomyocytes of young and old patients. Disturbed mitochondrial function was associated with signs of increased oxidative stress (protein carbonyl content, 8-hydroxy-2'-deoxyguanosine) as well as telomere shortening by up to 30%. Cardiomyocytes from older (obese and normal-weight) and young obese patients demonstrated higher levels of load-induced markers (atrial natriuretic peptide and brain natriuretic peptide) and proapoptotic activation with increased Bax and Bcl-xS expression, cytochrome C release, and caspase 3/9 activation. Disturbances in glucose metabolism and adipocytokine release were detectable in old (obese and normal-weight) and young obese patients. However, only minor deteriorations in most parameters were observed in obese subjects older than 70 years of age compared with normal-weight, age-matched patients.Conclusions These data indicate that obesity results in premature cardiac aging in younger patients, which may contribute to an increased risk for heart failure. (J Am Coll Cardiol 2011;57:577-85) (C) 2011 by the American College of Cardiology Foundation