Fol. Biol. 2000, 46, 233-240
Genetic Analysis of Cardiovascular Risk Factor Clustering in Spontaneous Hypertension
The SHR is the most widely studied animal model of hypertension. In this strain, as in many humans with essential hypertension, increased blood pressure has been reported to cluster with other risk factors for cardiovascular disease, including insulin resistance and dyslipidemia. However, the genetic mechanisms that mediate this clustering of risk factors for cardiovascular disease or the hypertension "metabolic syndrome" remain poorly understood. In the current studies, we have demonstrated (1) that a gene or genes responsible for a whole spectrum of cardiovascular risk factors mapped to a limited segment of the centromeric region of rat chromosome 4, (2) that a spontaneous deletion in the gene for Cd36 that encodes a fatty acid transporter and is located directly at the peak of QTL linkages on chromosome 4 has been indirectly linked to the transmission of insulin resistance, defective fatty acid metabolism, and increased blood pressure, and (3) based on complementation analysis in two transgenic lines expressing wild-type Cd36 on the genetic background of the SHR strain harboring the deletion variant of Cd36, we have established that defective Cd36 can be a determinant of disordered fatty acid metabolism, glucose intolerance, and insulin resistance in spontaneous hypertension.
Keywords
insulin resistance, dyslipidemia, hypertension, SHR-4 congenic strain, Cd36, Cd36-transgenic rats.
Funding
This work was supported by grants 305/00/1646 to V. Z., 301/00/1636 to M. P., and 204/98/K015 to M. P. and V. K from the Grant Agency of the Czech Republic, by the grant 4904-3 to L. K. from the ministry of Health of the Czech Republic, and by grants LN00A079 to M. P. and MSM 412100003.
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.