| First Author | Hölscher M | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 13 | Pages | 11185-94 |
| PubMed ID | 21270129 | Mgi Jnum | J:170943 |
| Mgi Id | MGI:4947919 | Doi | 10.1074/jbc.M110.186809 |
| Citation | Holscher M, et al. (2011) Cardiomyocyte-specific Prolyl-4-hydroxylase Domain 2 Knock Out Protects from Acute Myocardial Ischemic Injury. J Biol Chem 286(13):11185-94 |
| abstractText | Prolylhydroxylase 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-1alpha 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-1alpha 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. |
