Hoelscher, MarionMarionHoelscherSilter, MoniqueMoniqueSilterKrull, SabineSabineKrullvon Ahlen, MelanieMelanievon AhlenHesse, AmkeAmkeHesseSchwartz, Peter J.Peter J.SchwartzWielockx, BenBenWielockxBreier, GeorgGeorgBreierKatschinski, Doerthe MagdalenaDoerthe MagdalenaKatschinskiZieseniss, AnkeAnkeZieseniss2018-11-072018-11-072011https://resolver.sub.uni-goettingen.de/purl?gro-2/23434Prolylhydroxylase domain proteins (PHD) are cellular oxygen- sensing molecules that regulate the stability of the alpha-subunit of the transcription factor hypoxia inducible factor (HIF)-1. HIF-1 affects cardiac development as well as adaptation of the heart toward increased pressure overload or myocardial infarction. We have disrupted PHD2 in cardiomyocytes (cPhd(-/-)) using Phd2(flox/flox) mice in combination with MLCvCre mice, which resulted in HIF-1 alpha stabilization and activation of HIF target genes in the heart. Although cPhd2(-/-) mice showed no gross abnormalities in cardiac filament structure or function, we observed a significant increased cardiac capillary area in those mice. cPhd2(-/-) mice did not respond differently to increased mechanical load by transverse aortic constriction compared with their wild-type (wt) littermates. After ligation of the left anterior descending artery, however, the area at risk and area of necrosis were significantly smaller in the cPhd2(-/-) mice compared with Phd2 wt mice in line with the described pivotal role of HIF-1 alpha for tissue protection in case of myocardial infarction. This correlated with a decreased number of apoptotic cells in the infarcted myocardium in the cPhd2(-/-) mice and significantly improved cardiac function 3 weeks after myocardial infarction.journal_article10.1074/jbc.M110.18680921270129000288797100029