biostudies-literatureUnknown33(16)Kerkela RSmall-molecule inhibition of hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) is being explored for the treatment of anemia. Previous studies have suggested that HIF-P4H-2 inhibition may also protect the heart from an ischemic insult. Hif-p4h-2(gt/gt) mice, which have 76 to 93% knockdown of Hif-p4h-2 mRNA in endothelial cells, fibroblasts, and cardiomyocytes and normoxic stabilization of Hif-α, were subjected to ligation of the left anterior descending coronary artery (LAD). Hif-p4h-2 deficiency resulted in increased survival, better-preserved left ventricle (LV) systolic function, and a smaller infarct size. Surprisingly, a significantly larger area of the LV remained perfused during LAD ligation in Hif-p4h-2(gt/gt) hearts than in wild-type hearts. However, no difference was obseMolecular and cellular biology3321-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC3753900biostudies-literatureActivation of hypoxia response in endothelial cells contributes to ischemic cardioprotection.PMC3753900Pietila ISormunen RKoch WJGao EKoivunen PVainio LAlitalo KKivirikko KISerpi RAnisimov AMagga JMyllyharju JKerkela RSzabo ZKarsikas SfalseActivation of hypoxia response in endothelial cells contributes to ischemic cardioprotection.Small-molecule inhibition of hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) is being explored for the treatment of anemia. Previous studies have suggested that HIF-P4H-2 inhibition may also protect the heart from an ischemic insult. Hif-p4h-2(gt/gt) mice, which have 76 to 93% knockdown of Hif-p4h-2 mRNA in endothelial cells, fibroblasts, and cardiomyocytes and normoxic stabilization of Hif-α, were subjected to ligation of the left anterior descending coronary artery (LAD). Hif-p4h-2 deficiency resulted in increased survival, better-preserved left ventricle (LV) systolic function, and a smaller infarct size. Surprisingly, a significantly larger area of the LV remained perfused during LAD ligation in Hif-p4h-2(gt/gt) hearts than in wild-type hearts. However, no difference was obse2013-01-01T00:00:00Z2013 Aug2025-04-04T22:06:46.926Z2019-03-27T01:15:07ZS-EPMC37539002377512110.1128/MCB.00432-1310.1128/mcb.00432-13