Journal article
Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage
American journal of physiology. Heart and circulatory physiology, Vol.292(3), pp.H1398-1403
03/2007
Handle:
https://hdl.handle.net/2376/108421
PMID: 17085535
Abstract
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.
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Details
- Title
- Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage
- Creators
- Qun Li - Div of Pharmaceutical Science & Center for Cardiovascular Research and Alternative Medicine, Univ of Wyoming, Laramie, WY 82071-3375, USAShan WuShi-Yan LiFaye L LopezMin DuJan KajsturaPiero AnversaJun Ren
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.292(3), pp.H1398-1403
- Academic Unit
- Animal Sciences, Department of
- Publisher
- United States
- Grant note
- 1 R03-AG-21324-01 / NIA NIH HHS 1 R15-AA-13575-01 / NIAAA NIH HHS
- Identifiers
- 99900547752201842
- Language
- English
- Resource Type
- Journal article