Insulin-like growth factor-1 overexpression in cardiomyocytes diminishes ex vivo heart functional recovery after acute ischemia
Author
Prele, CM; Reichelt, ME; Mutsaers, SE; Davies, M; Delbridge, LM; Headrick, JP; Rosenthal, N; Bogoyevitch, MA; Grounds, MDDate
2012-01-01Source Title
CARDIOVASCULAR PATHOLOGYPublisher
ELSEVIER SCIENCE INCAffiliation
PhysiologyMetadata
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Journal ArticleCitations
Prele, C. M., Reichelt, M. E., Mutsaers, S. E., Davies, M., Delbridge, L. M., Headrick, J. P., Rosenthal, N., Bogoyevitch, M. A. & 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. https://doi.org/10.1016/j.carpath.2010.11.008.Access Status
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C1 - Journal Articles Refereed
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.
Keywords
Animal Physiology - Biophysics; Cardiovascular System and DiseasesExport Reference in RIS Format
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