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This Article Full Text Full Text (PDF) All Versions of this Article: 292/3/H1398    most recent 01036.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Li, Q. Articles by Ren, J. Search for Related Content PubMed PubMed Citation Articles by Li, Q. Articles by Ren, J.

Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage

¹Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine and ²Department of Animal Sciences, Laramie, Wyoming; and ³Department of Medicine, New York Medical College, Valhalla, New York

Submitted 21 September 2006 ; accepted in final form 31 October 2006

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 (TR₉₀), and maximal velocity of shortening/relengthening (±dL/dt). Levels of advanced glycation end product, protein carbonyl, sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA2a), phospholamban, and Na⁺/Ca²⁺ exchanger were assessed by Western blot analysis. SERCA activity was measured by ⁴⁵Ca²⁺ uptake. Aging induced a decline in plasma IGF-1 levels. Aged cells exhibited depressed ±dL/dt, prolonged TR₉₀, 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⁺/Ca²⁺ 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 Ca²⁺ uptake.

cardiomyocytes; contractile function; calcium regulatory protein; senescence

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				S.-J. Kim, M. Abdellatif, S. Koul, and G. J. Crystal Chronic treatment with insulin-like growth factor I enhances myocyte contraction by upregulation of Akt-SERCA2a signaling pathway Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H130 - H135. [Abstract] [Full Text] [PDF]