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Insulin-like growth factor-1 overexpression in cardiomyocytes diminishes ex vivo heart functional recovery after acute ischemia

Prêle, C.M., Reichelt, M.E., Mutsaers, S.E., Davies, M., Delbridge, L.M., Headrick, J.P., Rosenthal, N., Bogoyevitch, M.A. and Grounds, M.D. (2012) Insulin-like growth factor-1 overexpression in cardiomyocytes diminishes ex vivo heart functional recovery after acute ischemia. Cardiovascular Pathology, 21 (1). pp. 17-27.

Link to Published Version: https://doi.org/10.1016/j.carpath.2010.11.008
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Abstract

Background

Acute insulin-like growth factor-1 administration has been shown to have beneficial effects in cardiac pathological conditions. The aim of the present study was to assess the structural and ex vivo functional impacts of long-term cardiomyocyte-specific insulin-like growth factor-1 overexpression in hearts of transgenic αMHC-IGF-1 Ea mice.

Methods

Performance of isolated transgenic αMHC-IGF-1 Ea and littermate wild-type control hearts was compared under baseline conditions and in response to 20-min ischemic insult. Cardiac desmin and laminin expression patterns were determined histologically, and myocardial hydroxyproline was measured to assess collagen content.

Results

Overexpression of insulin-like growth factor-1 did not modify expression patterns of desmin or laminin but was associated with a pronounced increase (∼30%) in cardiac collagen content (from ∼3.7 to 4.8 μg/mg). Baseline myocardial contractile function and coronary flow were unaltered by insulin-like growth factor-1 overexpression. In contrast to prior evidence of acute cardiac protection, insulin-like growth factor-1 overexpression was associated with significant impairment of acute functional response to ischemia–reperfusion. Insulin-like growth factor-1 overexpression did not modify ischemic contracture development, but postischemic diastolic dysfunction was aggravated (51±5 vs. 22±6 mmHg in nontransgenic littermates). Compared with wild-type control, recovery of pressure development and relaxation indices relative to baseline performance were significantly reduced in transgenic αMHC-IGF-1 Ea after 60-min reperfusion (34±7% vs. 62±7% recovery of +dP/dt; 35±11% vs. 57±8% recovery of −dP/dt).

Conclusions

Chronic insulin-like growth factor-1 overexpression is associated with reduced functional recovery after acute ischemic insult. Collagen deposition is elevated in transgenic αMHC-IGF-1 Ea hearts, but there is no change in expression of the myocardial structural proteins desmin and laminin. These findings suggest that sustained cardiac elevation of insulin-like growth factor-1 may not be beneficial in the setting of an acute ischemic insult.

Item Type: Journal Article
Publisher: Elsevier
Copyright: © 2012 Elsevier Inc.
URI: http://researchrepository.murdoch.edu.au/id/eprint/64361
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