Hypoxia Attenuates Pressure Overload-Induced Heart Failure

BACKGROUND: Alveolar hypoxia is protective in the context of cardiovascular and ischemic heart disease; however, the underlying mechanisms are incompletely understood. The present study sought to test the hypothesis that hypoxia is cardioprotective in left ventricular pressure overload (LVPO)-induced heart failure. We furthermore aimed to test that overlapping mechanisms promote cardiac recovery in heart failure patients following left ventricular assist device-mediated mechanical unloading and circulatory support. METHODS AND RESULTS: We established a novel murine model of combined chronic alveolar hypoxia and LVPO following transverse aortic constriction (HxTAC). The HxTAC model is resistant to cardiac hypertrophy and the development of heart failure. The cardioprotective mechanisms identified in our HxTAC model include increased activation of HIF (hypoxia-inducible factor)-1

• Froese, N.
• Szaroszyk, M.
• Galuppo, P.
• Visker, J. R.
• Werlein, C.
• Korf-Klingebiel, M.
• Berliner, D.
• Reboll, M. R.
• Hamouche, R.
• Gegel, S.
• Wang, Y.
• Hofmann, W.
• Tang, M.
• Geffers, R.
• Wende, A. R.
• Kühnel, M. P.
• Jonigk, D. D.
• Hansmann, G.
• Wollert, K. C.
• Abel, E. D.
• Drakos, S. G.
• Bauersachs, J.
• Riehle, C.