Role of VEGF in maintaining renal structure and function under normotensive and hypertensive conditions.

  1. Lookup NU author(s)
  2. Dr Andrew Advani
  3. Suzanne Advani
  4. Dr Kathryn White
  5. Professor Sally Marshall
Author(s)Advani A, Kelly DJ, Advani SL, Cox AJ, Thai K, Zhang Y, White KE, Gow RM, Marshall SM, Steer BM, Marsden PA, Rakoczy PE, Gilbert RE
Publication type Article
JournalProceedings of the National Academy of Sciences of the United States of America
Year2007
Volume104
Issue36
Pages14448-14453
ISSN (print)0027-8424
ISSN (electronic)1091-6490
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Inhibiting the actions of VEGF is a new therapeutic paradigm in cancer management with antiangiogenic therapy also under intensive investigation in a range of nonmalignant diseases characterized by pathological angiogenesis. However, the effects of VEGF inhibition on organs that constitutively express it in adulthood, such as the kidney, are mostly unknown. Accordingly, we examined the effect of VEGF inhibition on renal structure and function under physiological conditions and in the setting of the common renal stressors: hypertension and activation of the renin–angiotensin system. When compared with normotensive Sprague–Dawley (SD) rats, glomerular VEGF mRNA was increased 2-fold in transgenic (mRen-2)27 rats that overexpress renin with spontaneously hypertensive rat (SHR) kidneys showing VEGF expression levels that were intermediate between them. Administration of either an orally active inhibitor of the type 2 VEGF receptor (VEGFR-2) tyrosine kinase or a VEGF neutralizing antibody to TGR(mRen-2)27 rats resulted in loss of glomerular endothelial cells and transformation to a malignant hypertensive phenotype with severe glomerulosclerosis. VEGFR-2 kinase inhibition treatment was well tolerated in SDs and SHRs; although even in these animals there was detectable endothelial cell loss and rise in albuminuria. Mild mesangial expansion was also noted in hypertensive SHR, but not in SD rats. These studies illustrate: (i) VEGF has a role in the maintenance of glomerular endothelial integrity under physiological circumstances, (ii) glomerular VEGF is increased in response to hypertension and activation of the renin–angiotensin system, and (iii) VEGF signaling plays a protective role in the setting of these renal stressors.
PublisherNational Academy of Sciences
URLhttp://dx.doi.org/10.1073/pnas.0703577104
DOI10.1073/pnas.0703577104
Actions    Link to this publication