Impaired Ca2+-handling in HIF-1 alpha(+/-) mice as a consequence of pressure overload
2010 | journal article. A publication with affiliation to the University of Göttingen.
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Impaired Ca2+-handling in HIF-1 alpha(+/-) mice as a consequence of pressure overload
Silter, M.; Koegler, H.; Zieseniss, A.; Wilting, J.; Schaefer, K. ; Toischer, K. & Rokita, A. G. et al. (2010)
Pflügers Archiv - European Journal of Physiology, 459(4) pp. 569-577. DOI: https://doi.org/10.1007/s00424-009-0748-x
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Details
- Authors
- Silter, Monique; Koegler, Harald; Zieseniss, Anke; Wilting, Joerg; Schaefer, Katrin ; Toischer, Karl ; Rokita, Adam G.; Breves, Gerhard; Maier, Lars S. ; Katschinski, Doerthe Magdalena
- Abstract
- The hypoxia-inducible factor (HIF)-1 is critically involved in the cellular adaptation to a decrease in oxygen availability. The influence of HIF-1 alpha for the development of cardiac hypertrophy and cardiac function that occurs in response to sustained pressure overload has been mainly attributed to a challenged cardiac angiogenesis and cardiac hypertrophy up to now. Hif-1 alpha (+/+) and Hif-1 alpha (+/-) mice were studied regarding left ventricular hypertrophy and cardiac function after being subjected to transverse aortic constriction (TAC). After TAC, both Hif-1 alpha (+/+) and Hif-1 alpha (+/-) mice developed left ventricular hypertrophy with increased posterior wall thickness, septum thickness and increased left ventricular weight to a similar extent. No significant difference in cardiac vessel density was observed between Hif-1 alpha (+/+) and Hif-1 alpha (+/-) mice. However, only the Hif-1 alpha (+/-) mice developed severe heart failure as revealed by a significantly reduced fractional shortening mostly due to increased end-systolic left ventricular diameter. On the single cell level this correlated with reduced myocyte shortenings, decreased intracellular Ca2+-transients and SR-Ca2+ content in myocytes of Hif-1a (+/-) mice. Thus, HIF-1 alpha can be critically involved in the preservation of cardiac function after chronic pressure overload without affecting cardiac hypertrophy. This effect is mediated via HIF-dependent modulation of cardiac calcium handling and contractility.
- Issue Date
- 2010
- Status
- published
- Publisher
- Springer
- Journal
- Pflügers Archiv - European Journal of Physiology
- ISSN
- 0031-6768