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首页> 外文期刊>American Journal of Physiology >Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage.
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Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage.

机译：心脏样胰岛素样生长因子1的特定心脏过度表达可减轻与衰老相关的心脏舒张收缩功能障碍和蛋白质损伤。

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摘要

Aging is associated with hepatic growth hormone resistance resulting in a fall in serum insulin-like growth factor 1 (IGF-1) level. However, whether loss of IGF-1 contributes to cardiac aging is unclear. This study was designed to examine the effect of cardiac overexpression of IGF-1 on cardiomyocyte contractile function in young (3 mo) and old (26-28 mo) mice. Cardiomyocyte contractile function was evaluated, including peak shortening (PS), time to 90% PS, time to 90% relengthening (TR(90)), and maximal velocity of shortening/relengthening (+/-dL/dt). Levels of advanced glycation end product, protein carbonyl, sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), phospholamban, and Na(+)/Ca(2+) exchanger were assessed by Western blot analysis. SERCA activity was measured by (45)Ca(2+) uptake. Aging induced a decline in plasma IGF-1 levels. Aged cells exhibited depressed +/-dL/dt, prolonged TR(90), and a steeper PS decline in response to increasing stimulus frequency compared with those in young myocytes. IGF-1 transgene alleviated aging-induced loss in plasma IGF-1 and aging-induced mechanical defects with little effect in young mice. The beneficial effect of IGF-1 transgene on aging-associated cardiomyocyte contractile dysfunction was somewhat mimicked by short-term in vitro treatment of recombinant IGF-1 (500 nM). Advanced glycation end product and protein carbonyl levels were higher in aged mice, which were not affected by IGF-1. Expression of SERCA2a (but not Na(+)/Ca(2+) exchanger and phospholamban) and SERCA activity were reduced with aging, which was ablated by the IGF-1 transgene. Collectively, our data suggest a beneficial role of IGF-1 in aging-induced cardiac contractile dysfunction, possibly related to improved Ca(2+) uptake.
机译：衰老与肝脏生长激素抵抗相关，导致血清胰岛素样生长因子1（IGF-1）水平下降。但是，尚不清楚IGF-1的丢失是否会导致心脏衰老。这项研究旨在检查IGF-1的心脏过表达对年轻（3 mo）和老龄（26-28 mo）小鼠心肌收缩功能的影响。评估心肌细胞的收缩功能，包括峰缩短（PS），达到90％PS的时间，达到90％延长的时间（TR（90））和最大缩短/延长的速度（+/- dL / dt）。通过蛋白质印迹分析评估了高级糖基化终产物，蛋白质羰基，肌质网Ca（2 +）-ATPase（SERCA2a），磷酰胺和Na（+）/ Ca（2+）交换剂的水平。 SERCA活性通过（45）Ca（2+）吸收来测量。衰老引起血浆IGF-1水平下降。与年轻的肌细胞相比，老化的细胞表现出降低的+/- dL / dt，延长的TR（90）和对刺激频率增加的更陡峭的PS下降。 IGF-1转基因减轻了衰老诱导的血浆IGF-1的损失和衰老诱导的机械缺陷，对年轻小鼠几乎没有影响。通过短期体外重组IGF-1（500 nM）的体外治疗，IGF-1转基因对衰老相关的心肌收缩功能异常的有益作用被模仿。老年小鼠的晚期糖基化终产物和蛋白质羰基水平较高，不受IGF-1的影响。 SERCA2a（但不是Na（+）/ Ca（2+）交换子和phosphorlamban除外）的表达和SERCA活性随衰老而降低，这被IGF-1转基因消除了。总的来说，我们的数据表明，IGF-1在衰老诱导的心脏收缩功能障碍中可能起有益作用，可能与改善的Ca（2+）吸收有关。

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