Transgenic Expression of CD36 in the Spontaneously Hypertensive Rat Is Associated with Amelioration of Metabolic Disturbances But Has No Effect on Hypertension    

M. PRAVENEC^1,2, V. LANDA¹, V. ZÍDEK¹, A. MUSILOVÁ¹, L. KAZDOVÁ³, N. QI⁴, J. WANG⁴, E. ST. LEZIN^4,5, T. W. KURTZ⁴

¹Institute of Physiology, Czech Academy of Sciences and Center for Integrated Genomics, ²Institute of Biology and Medical Genetics, First Medical Faculty, Charles University, ³Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ⁴Department of Laboratory Medicine, University of California and ⁵Department of Veterans Affairs Medical Center, San Francisco, CA, USA

Received August 29, 2002
Accepted November 25, 2002

Summary
Spontaneously hypertensive rats (SHR/NIH strain) harbor a deletion variant in the Cd36 fatty acid transporter and display defective fatty acid metabolism, insulin resistance and hypertension. Transgenic rescue of Cd36 in SHR ameliorates insulin resistance and improves dyslipidemia. However, the role of Cd36 in blood pressure regulation remains controversial due to inconsistent blood pressure effects that were observed with transgenic expression of Cd36 on the SHR background. In the current studies, we developed two new SHR transgenic lines, which express wild type Cd36 under the control of the universal Ef-1 promoter, and examined the effects of transgenic expression of wild type Cd36 on selected metabolic and cardiovascular phenotypes. Transgenic expression of Cd36 in the new lines was associated with significantly decreased serum fatty acids, amelioration of insulin resistance and glucose intolerance but failed to induce any consistent changes in blood pressure as measured by radiotelemetry. The current findings confirm the genetic association of defective Cd36 with disordered insulin action and fatty acid metabolism in the SHR/NIH strain and suggest that Cd36 is linked to other gene(s) on rat chromosome 4 that regulate blood pressure.

Key words
SHR • Cd36 • Transgenic animal • Blood pressure • Insulin resistance • Fatty acids