Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension
M Pravenec, V Zidek, M Simakova… - The Journal of …, 1999 - Am Soc Clin Investig
M Pravenec, V Zidek, M Simakova, V Kren, D Krenova, K Horky, M Jachymova, B Mikova…
The Journal of clinical investigation, 1999•Am Soc Clin InvestigDisorders of carbohydrate and lipid metabolism have been reported to cluster in patients
with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in
the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate
and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and
chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in
SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a …
with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in
the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate
and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and
chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in
SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a …
Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR.BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR.BN-Il6/Npy strain.
J. Clin. Invest. 103:1651–1657 (1999).
The Journal of Clinical Investigation