title: Age-related changes in cardiac expression of VEGF and its angiogenic receptor KDR in stroke-prone spontaneously hypertensive rats.
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.
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Subrina
authors: S
authors: Jesmin
authors: Yuichi
authors: Y
authors: Hattori
authors: Hiroko
authors: H
authors: Togashi
authors: Ken-ichi
authors: K
authors: Ueno
authors: Mitsuhiro
authors: M
authors: Yoshioka
authors: Ichiro
authors: I
authors: Sakuma
mesh_terms: D000367:Age Factors; D000818:Animals; D002196:Capillaries / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism; D003331:Coronary Vessels / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D020521:Stroke / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D040301:Vascular Endothelial Growth Factor Receptor-2