Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity.
Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity.
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DOI：
10.1038/oby.2008.414
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Ballantyne CM
中科院分区：
文献类型：
--
作者：
Thakker GD;Frangogiannis NG;Zymek PT;Sharma S;Raya JL;Barger PM;Taegtmeyer H;Entman ML;Ballantyne CM
肥胖和糖尿病经常与心血管疾病有关。当正常心脏遭受短暂/亚致死重复缺血和再灌注（I/R）时，适应性反应会被激活，以保护心脏结构和功能。这些反应包括但不限于心脏代谢的改变、钙反应性降低和抗氧化酶的诱导。在短暂重复I/R诱导的缺血性心肌病模型中，我们假设饮食诱导肥胖（DIO）小鼠的这些适应性反应失调将有助于增强心肌损伤。DIO C57 BL/6 J小鼠在短效麻醉下接受15分钟的每日重复I/R，这是一种导致纤维化心肌病发展的方案。在重复I/R的第3天分析心脏脂质和候选基因表达，并在第5天分析组织学。DIO小鼠心脏提取物中的总游离脂肪酸（FFA）显著升高，主要反映了膳食脂肪酸组成。与瘦对照组相比，DIO小鼠心脏脂肪酸氧化能力显著升高，同时脂肪酸代谢基因转录本表达增加。每天重复I/R 15分钟，持续3或5天后，DIO小鼠表现出对I/R的敏感性增加，与瘦小鼠相反，出现了微梗死，这与夸大的炎症反应有关。DIO小鼠的重复I/R与脂肪酸代谢基因转录的更深刻的显着下调和升高的FFA和甘油三酯相关。脂肪酸代谢的不适应性代谢变化有助于饮食诱导的肥胖症中增强的心肌损伤。
Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol that results in the development of fibrotic cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3 days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in the cardiac extracts of DIO mice were significantly elevated, reflecting primarily the dietary fatty acid composition. Compared with lean controls, cardiac fatty acid oxidation capacity of DIO mice was significantly higher, concurrent with increased expression of fatty acid metabolism gene transcripts. Following 15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased susceptibility to I/R and, in contrast to lean mice, developed microinfarction, which was associated with an exaggerated inflammatory response. Repetitive I/R in DIO mice was associated with more profound significant downregulation of fatty acid metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive metabolic changes of fatty acid metabolism contribute to enhanced myocardial injury in diet-induced obesity.
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影响因子：
4.8
作者：
Sharma, S;Adrogue, JV;Taegtmeyer, H
通讯作者：
Taegtmeyer, H
DOI：
10.1152/ajpheart.2000.278.4.h1345
发表时间：
2000-04-01
影响因子：
4.8
作者：
Korvald, C;Elvenes, OP;Myrmel, T
通讯作者：
Myrmel, T
DOI：
10.1006/bbrc.2001.5541
发表时间：
2001-09-14
影响因子：
3.1
作者：
Razeghi, P;Young, ME;Taegtmeyer, H
通讯作者：
Taegtmeyer, H
影响因子：
4.2
作者：
Ajuwon, KM;Spurlock, ME
通讯作者：
Spurlock, ME
DOI：
10.1254/jjp.77.137
发表时间：
1998-06-01
期刊：
JAPANESE JOURNAL OF PHARMACOLOGY
影响因子：
--
作者：
Nasa, Y;Hayashi, M;Takeo, S
通讯作者：
Takeo, S