Molecular and Cellular Biochemistry

, Volume 272, Issue 1–2, pp 63–73 | Cite as

Age-related changes in cardiac expression of VEGF and its angiogenic receptor KDR in stroke-prone spontaneously hypertensive rats

  • Subrina Jesmin
  • Yuichi Hattori
  • Hiroko Togashi
  • Ken-Ichi Ueno
  • Mitsuhiro Yoshioka
  • Ichiro Sakuma


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-β1 (TGF-β1) 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-β1, 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.


cardiac remodeling coronary vessels endothelial nitric oxide synthase hypertension transforming growth factor-β1 vascular endothelial growth factor 


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Subrina Jesmin
    • 1
  • Yuichi Hattori
    • 2
  • Hiroko Togashi
    • 2
  • Ken-Ichi Ueno
    • 2
  • Mitsuhiro Yoshioka
    • 2
  • Ichiro Sakuma
    • 1
    • 3
  1. 1.Department of Cardiovascular MedicineHokkaido University Graduate School of MedicineSapporoJapan
  2. 2.Department of PharmacologyHokkaido University Graduate School of MedicineSapporoJapan
  3. 3.Department of Cardiovascular MedicineHokkaido University Graduate School of MedicineSapporoJapan

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