CD36 expression contributes to age-induced cardiomyopathy in mice
CD36 expression contributes to age-induced cardiomyopathy in mice
复制标题
DOI：
10.1161/circulationaha.107.712901
复制
发表时间：
2007-11-06
期刊：
影响因子：
37.8
通讯作者：
Dyck, Jason R. B.
中科院分区：
文献类型：
--
作者：
Koonen, Debby P. Y.;Febbraio, Maria;Dyck, Jason R. B.
背景——老年人的心脏重塑和心脏功能受损会显着增加患心脏病的风险。虽然与衰老相关的血管异常会导致与年龄相关的心脏功能下降，但也可能涉及心肌特异性事件。 方法和结果 - 我们发现，老年小鼠也会发生心肌内脂质积累、脂肪酸和葡萄糖氧化减少以及随后的心脏 ATP 供应恶化。与能量受损的心脏一致，老年小鼠的心脏表现出心肌性能下降和心脏肥大。与此相关的是，与年轻心脏相比，老年心脏中脂肪酸转运蛋白 CD36 显着增加，这表明 CD36 是老年心脏中这些多重代谢、功能和结构改变的介质。据此，老年 CD36 缺陷小鼠的心脏心肌内脂质水平较低，线粒体来源的 ATP 生成有所改善，与老年野生型小鼠相比，其功能显着增强，并且肥厚反应减弱。结论 - 这些发现提供了 CD36 介导小鼠年龄诱发的心肌病的证据，并表明抑制 CD36 可能是治疗年龄相关对心脏功能的有害影响的一种方法。
Background - Cardiac remodeling and impaired cardiac performance in the elderly significantly increase the risk of developing heart disease. Although vascular abnormalities associated with aging contribute to the age-related decline in cardiac function, myocardium-specific events may also be involved.Methods and Results - We show that intramyocardial lipid accumulation, as well as a reduction in both fatty acid and glucose oxidation and a subsequent deterioration in cardiac ATP supply, also occurs in aged mice. Consistent with an energetically compromised heart, hearts from aged mice display depressed myocardial performance and cardiac hypertrophy. Associated with this is a dramatic increase in the fatty acid transport protein CD36 in aged hearts compared with young hearts, which suggests that CD36 is a mediator of these multiple metabolic, functional, and structural alterations in the aged heart. In accordance with this, hearts from aged CD36-deficient mice have lower levels of intramyocardial lipids, demonstrate improved mitochondria-derived ATP production, have significantly enhanced function compared with aged wild-type mice, and have a blunted hypertrophic response.Conclusions - These findings provide evidence that CD36 mediates an age-induced cardiomyopathy in mice and suggest that inhibition of CD36 may be an approach for the treatment of the detrimental age-related effects on cardiac performance.