Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease.
Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease.
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DOI：
10.1007/s00109-010-0663-9
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发表时间：
2010-10
影响因子：
4.7
通讯作者：
Sowers, James R.
中科院分区：
文献类型：
--
作者：
Ren, Jun;Pulakat, Lakshmi;Whaley-Connell, Adam;Sowers, James R.
代谢综合征是一系列代谢紊乱，包括肥胖、高血压和胰岛素抵抗，这些是糖尿病、高血压、心血管和肾脏疾病发展的危险因素。导致代谢综合征发生的病理生理异常包括线粒体氧化磷酸化和线粒体生物合成受损、胰岛素代谢信号传导减弱、内皮功能障碍和相关的心肌功能异常。最近的证据表明，心肌线粒体生物合成、脂肪酸代谢和抗氧化防御机制受损导致心脏底物灵活性降低、心脏能量效率降低和舒张功能障碍。此外，增强的肾素-血管紧张素-醛固酮系统的活化和相关的氧化应激增加可导致线粒体凋亡和降解、改变的生物能量学和脂质在心脏中的积累。除了代谢信号传导和氧化应激的损伤之外，遗传和环境因素、衰老和高血糖症都有助于减少线粒体生物合成和线粒体功能障碍。这些线粒体异常可诱发以舒张功能障碍为特征的代谢性心肌病。线粒体功能障碍和导致的骨骼肌、肝脏和胰腺中的脂质积聚也阻碍胰岛素代谢信号传导和葡萄糖代谢，最终导致线粒体功能障碍的进一步增加。改善线粒体功能的干预措施已被证明可以纠正胰岛素代谢信号传导和其他代谢和心血管异常。本文综述了代谢性心脏病病理生理学中线粒体功能障碍的机制，重点是氧化磷酸化受损和线粒体生物合成。
The metabolic syndrome is a constellation of metabolic disorders including obesity, hypertension, and insulin resistance, components which are risk factors for the development of diabetes, hypertension, cardiovascular, and renal disease. Pathophysiological abnormalities that contribute to the development of the metabolic syndrome include impaired mitochondrial oxidative phosphorylation and mitochondrial biogenesis, dampened insulin metabolic signaling, endothelial dysfunction, and associated myocardial functional abnormalities. Recent evidence suggests that impaired myocardial mitochondrial biogenesis, fatty acid metabolism, and antioxidant defense mechanisms lead to diminished cardiac substrate flexibility, decreased cardiac energetic efficiency, and diastolic dysfunction. In addition, enhanced activation of the renin–angiotensin–aldosterone system and associated increases in oxidative stress can lead to mitochondrial apoptosis and degradation, altered bioenergetics, and accumulation of lipids in the heart. In addition to impairments in metabolic signaling and oxidative stress, genetic and environmental factors, aging, and hyperglycemia all contribute to reduced mitochondrial biogenesis and mitochondrial dysfunction. These mitochondrial abnormalities can predispose a metabolic cardiomyopathy characterized by diastolic dysfunction. Mitochondrial dysfunction and resulting lipid accumulation in skeletal muscle, liver, and pancreas also impede insulin metabolic signaling and glucose metabolism, ultimately leading to a further increase in mitochondrial dysfunction. Interventions to improve mitochondrial function have been shown to correct insulin metabolic signaling and other metabolic and cardiovascular abnormalities. This review explores mechanisms of mitochondrial dysfunction with a focus on impaired oxidative phosphorylation and mitochondrial biogenesis in the pathophysiology of metabolic heart disease.
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影响因子：
8.2
作者：
Makino, A.;Scott, B. T.;Dillmann, W. H.
通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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DOI：
10.1152/ajpheart.00313.2002
发表时间：
2002-10-01
影响因子：
4.8
作者：
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Matlib, MA
影响因子：
20.1
作者：
Flagg, Thomas P.;Cazorla, Olivier;Nerbonne, Jeanne M.
通讯作者：
Nerbonne, Jeanne M.
DOI：
10.1073/pnas.0337639100
发表时间：
2003-02-18
影响因子：
11.1
作者：
Czubryt, MP;McAnally, J;Olson, EN
通讯作者：
Olson, EN