Hypoxia-inducible Factor 1 and Cardiovascular Disease

Overview

Journal Annu Rev Physiol

Publisher Annual Reviews

Specialty Physiology

Date 2013 Aug 31

PMID 23988176

Citations 312

Authors

Gregg L Semenza

Affiliations

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Abstract

Cardiac function is required for blood circulation and systemic oxygen delivery. However, the heart has intrinsic oxygen demands that must be met to maintain effective contractility. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis in all metazoan species. HIF-1 controls oxygen delivery, by regulating angiogenesis and vascular remodeling, and oxygen utilization, by regulating glucose metabolism and redox homeostasis. Analysis of animal models suggests that by activation of these homeostatic mechanisms, HIF-1 plays a critical protective role in the pathophysiology of ischemic heart disease and pressure-overload heart failure.

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References

Kim J, Tchernyshyov I, Semenza G, Dang C . HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006; 3(3):177-85. DOI: 10.1016/j.cmet.2006.02.002. View

Ceradini D, Kulkarni A, Callaghan M, Tepper O, Bastidas N, Kleinman M . Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004; 10(8):858-64. DOI: 10.1038/nm1075. View

Sarkar K, Cai Z, Gupta R, Parajuli N, Fox-Talbot K, Darshan M . Hypoxia-inducible factor 1 transcriptional activity in endothelial cells is required for acute phase cardioprotection induced by ischemic preconditioning. Proc Natl Acad Sci U S A. 2012; 109(26):10504-9. PMC: 3387090. DOI: 10.1073/pnas.1208314109. View

Higgins D, Biju M, Akai Y, Wutz A, Johnson R, Haase V . Hypoxic induction of Ctgf is directly mediated by Hif-1. Am J Physiol Renal Physiol. 2004; 287(6):F1223-32. DOI: 10.1152/ajprenal.00245.2004. View

Forsythe J, Jiang B, Iyer N, Agani F, Leung S, Koos R . Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996; 16(9):4604-13. PMC: 231459. DOI: 10.1128/MCB.16.9.4604. View

Duran J, Gotzens V, Carballo J, Martin E, Petit M, Cordero A . The HIF1A C85T single nucleotide polymorphism influences the number of branches of the human coronary tree. Cardiology. 2012; 121(3):156-9. DOI: 10.1159/000336818. View

Murry C, Jennings R, Reimer K . Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986; 74(5):1124-36. DOI: 10.1161/01.cir.74.5.1124. View

Marber M, Latchman D, Walker J, Yellon D . Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction. Circulation. 1993; 88(3):1264-72. DOI: 10.1161/01.cir.88.3.1264. View

Krishnan J, Suter M, Windak R, Krebs T, Felley A, Montessuit C . Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metab. 2009; 9(6):512-24. DOI: 10.1016/j.cmet.2009.05.005. View

10.

Gess B, Hofbauer K, Deutzmann R, Kurtz A . Hypoxia up-regulates triosephosphate isomerase expression via a HIF-dependent pathway. Pflugers Arch. 2004; 448(2):175-80. DOI: 10.1007/s00424-004-1241-1. View

11.

Lee S, Wolf P, Escudero R, Deutsch R, Jamieson S, Thistlethwaite P . Early expression of angiogenesis factors in acute myocardial ischemia and infarction. N Engl J Med. 2000; 342(9):626-33. DOI: 10.1056/NEJM200003023420904. View

12.

Wei H, Bedja D, Koitabashi N, Xing D, Chen J, Fox-Talbot K . Endothelial expression of hypoxia-inducible factor 1 protects the murine heart and aorta from pressure overload by suppression of TGF-β signaling. Proc Natl Acad Sci U S A. 2012; 109(14):E841-50. PMC: 3325701. DOI: 10.1073/pnas.1202081109. View

13.

Lehman J, Kelly D . Gene regulatory mechanisms governing energy metabolism during cardiac hypertrophic growth. Heart Fail Rev. 2002; 7(2):175-85. DOI: 10.1023/a:1015332726303. View

14.

Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouyssegur J . Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol. 2009; 29(10):2570-81. PMC: 2682037. DOI: 10.1128/MCB.00166-09. View

15.

Sowter H, Ratcliffe P, Watson P, Greenberg A, Harris A . HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res. 2001; 61(18):6669-73. View

16.

Jean J, Rich C, Joyce-Brady M . Hypoxia results in an HIF-1-dependent induction of brain-specific aldolase C in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2006; 291(5):L950-6. DOI: 10.1152/ajplung.00087.2006. View

17.

Xia X, Lemieux M, Li W, Carroll J, Brown M, Liu X . Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proc Natl Acad Sci U S A. 2009; 106(11):4260-5. PMC: 2657396. DOI: 10.1073/pnas.0810067106. View

18.

Minchenko O, Opentanova I, Caro J . Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene family (PFKFB-1-4) expression in vivo. FEBS Lett. 2003; 554(3):264-70. DOI: 10.1016/s0014-5793(03)01179-7. View

19.

Armstrong S, GANOTE C . Adenosine receptor specificity in preconditioning of isolated rabbit cardiomyocytes: evidence of A3 receptor involvement. Cardiovasc Res. 1994; 28(7):1049-56. DOI: 10.1093/cvr/28.7.1049. View

20.

Wang G, Jiang B, Rue E, Semenza G . Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995; 92(12):5510-4. PMC: 41725. DOI: 10.1073/pnas.92.12.5510. View