RRC ID 162
Author Jesmin S, Hattori Y, Togashi H, Ueno K, Yoshioka M, Sakuma I.
Title Age-related changes in cardiac expression of VEGF and its angiogenic receptor KDR in stroke-prone spontaneously hypertensive rats.
Journal Mol. Cell. Biochem.
Abstract We examined the age-related changes in cardiac expression of angiogenic molecules during the development of cardiac remodeling in stroke-prone spontaneously hypertensive rats (SHRSP) in comparison with those in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Vascular endothelial growth factor (VEGF) was highly upregulated in SHRSP aged 20 weeks compared with the same age of WKY, but it was downregulated at 40 weeks. On the other hand, KDR, an angiogenic receptor of VEGF, and endothelial nitric oxide synthase, which is important in the VEGF-mediated angiogenic pathway, were markedly downregulated in SHRSP from 20 weeks of age. Such age-related changes in their expression levels seen in SHRSP were quite different from those in SHR. In both SHR and SHRSP, transforming growth factor-beta1 (TGF-beta1) expression was increased with age, although SHRSP showed more marked upregulation. Cardiac remodeling in SHRSP was characterized by decreased coronary capillary density, cardiomyocyte hypertrophy, and cardiac fibrosis. We conclude that, in addition to overexpression of TGF-beta1, which appears to play a pivotal role in promoting cardiac hypertrophy and fibrosis, a defect of the VEGF-KDR system could result in impaired physiologic coronary angiogenesis in SHRSP, contributing to cardiac deteroration associated with myocardial ischemia in this malignant hypertensive model.
Volume 272(1-2)
Pages 63-73
Published 2005-4
PMID 16010973
MeSH Age Factors Animals Capillaries / physiology Cardiomegaly / etiology Cardiomegaly / metabolism Coronary Vessels / immunology Coronary Vessels / metabolism* Down-Regulation Fibrosis / metabolism Fibrosis / pathology Gene Expression Heart Ventricles / metabolism Heart Ventricles / pathology Hypertension / complications Hypertension / genetics Hypertension / metabolism* Myocardium / metabolism* Myocardium / pathology Neovascularization, Physiologic Nitric Oxide Synthase / genetics Nitric Oxide Synthase / metabolism Nitric Oxide Synthase Type III Rats Rats, Inbred SHR Rats, Wistar Stroke / genetics Stroke / metabolism Transforming Growth Factor beta / genetics Transforming Growth Factor beta / metabolism Transforming Growth Factor beta1 Up-Regulation Vascular Endothelial Growth Factor A / analysis Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor A / metabolism* Vascular Endothelial Growth Factor Receptor-2 / analysis Vascular Endothelial Growth Factor Receptor-2 / genetics Vascular Endothelial Growth Factor Receptor-2 / metabolism*
IF 2.884
Times Cited 17