Lack of JunD Promotes Pressure Overload–Induced Apoptosis, Hypertrophic Growth, and Angiogenesis in the Heart
Open Access
- 6 September 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 112 (10), 1470-1477
- https://doi.org/10.1161/circulationaha.104.518472
Abstract
Background— The Jun family of activator protein 1 (AP-1) transcription factors (c-Jun, JunB, and JunD) is involved in fundamental biological processes such as proliferation, apoptosis, tumor angiogenesis, and hypertrophy. The role of individual AP-1 transcription factors in the stressed heart is not clear. In the present study we analyzed the role of JunD in survival, hypertrophy, and angiogenesis in the pressure-overloaded mouse heart after thoracic aortic constriction. Methods and Results— Mice lacking JunD (knockout [KO]) showed increased mortality and enhanced cardiomyocyte apoptosis and fibrosis associated with increased levels of hypoxia-induced factor-1α, vascular endothelial growth factor (VEGF), p53, and Bax protein and reduced levels of Bcl-2 protein after 7 days of severe pressure overload compared with wild-type (WT) siblings. Cardiomyocyte hypertrophy in surviving KO mice was enhanced compared with that in WT mice. Chronic moderate pressure overload for 12 weeks caused enhanced left ventricular hypertrophy in KO mice, and survival and interstitial fibrosis were comparable with WT mice. Cardiac function, 12 weeks after operation, was comparable among shams and pressure-overloaded mice of both genotypes. In addition, KO mice exposed to chronic pressure overload showed higher cardiac capillary density associated with increased protein levels of VEGF. Conclusions— Thus, JunD limits cardiomyocyte hypertrophy and protects the pressure-overloaded heart from cardiac apoptosis. These beneficial effects of JunD, however, are associated with antiangiogenic properties.Keywords
This publication has 39 references indexed in Scilit:
- Regulation of Proangiogenic Factor CCN1 in Cardiac MuscleCirculation, 2004
- Role of interleukin‐6 for left ventricular remodeling and survival after experimental myocardial infarctionThe FASEB Journal, 2003
- c-Jun N-terminal kinase is involved in motility of endothelial cellExperimental & Molecular Medicine, 2001
- Transcription activator protein 1 (AP‐1) mediates NO‐induced apoptosis of adult cardiomyocytesThe FASEB Journal, 2001
- JunD Regulates Transcription of the Tissue Inhibitor of Metalloproteinases-1 and Interleukin-6 Genes in Activated Hepatic Stellate CellsPublished by Elsevier BV ,2001
- AP-1 in mouse development and tumorigenesisOncogene, 2001
- Angiotensin Blockade Inhibits Increased JNKs, AP-1 and NF- κ B DNA-binding Activities in Myocardial Infarcted RatsJournal of Molecular and Cellular Cardiology, 2001
- The MEKK-JNK Pathway Is Stimulated by α1-Adrenergic Receptor and Ras Activation and Is Associated with in Vitro and in Vivo Cardiac HypertrophyJournal of Biological Chemistry, 1997
- Immediate-early Gene Responses to Different Cardiac Loads in the Ejecting Rabbit Left VentricleJournal of Molecular and Cellular Cardiology, 1996
- Prognostic Implications of Echocardiographically Determined Left Ventricular Mass in the Framingham Heart StudyNew England Journal of Medicine, 1990