Journal article
Insulin-like growth factor-1 overexpression in cardiomyocytes diminishes ex vivo heart functional recovery after acute ischemia
Cardiovascular Pathology, Vol.21(1), pp.17-27
2012
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.
Details
- Title
- Insulin-like growth factor-1 overexpression in cardiomyocytes diminishes ex vivo heart functional recovery after acute ischemia
- Authors/Creators
- C.M. Prêle (Author/Creator) - The University of Western AustraliaM.E. Reichelt (Author/Creator) - The University of MelbourneS.E. Mutsaers (Author/Creator) - The University of Western AustraliaM. Davies (Author/Creator) - The University of Western AustraliaL.M. Delbridge (Author/Creator) - The University of MelbourneJ.P. Headrick (Author/Creator) - Griffith UniversityN. Rosenthal (Author/Creator) - European Molecular Biology LaboratoryM.A. Bogoyevitch (Author/Creator) - The University of MelbourneM.D. Grounds (Author/Creator) - The University of Western Australia
- Publication Details
- Cardiovascular Pathology, Vol.21(1), pp.17-27
- Publisher
- Elsevier
- Identifiers
- 991005546326407891
- Copyright
- © 2012 Elsevier Inc.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.164 Endocrinology & Metabolism
- 1.164.287 GH/IGF Axis
- Web Of Science research areas
- Cardiac & Cardiovascular Systems
- Pathology
- ESI research areas
- Clinical Medicine