Abstract
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 Broom 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1651-1657 |
| Number of pages | 7 |
| Journal | Journal of Clinical Investigation |
| Volume | 103 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 1999 |
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ASJC Scopus subject areas
- Medicine(all)
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Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension. / Pravenec, Michal; Zidek, Vaclav; Simakova, Miroslava; Kren, Vladimir; Krenova, Drahomira; Horky, Karel; Jachymova, Marie; Mikova, Blanka; Kazdova, Ludmila; Aitman, Timothy J.; Churchill, Paul C.; Webb, R. Clinton; Hingarh, Nilesh H.; Yang, Ying; Wang, Jia Ming; St. Lezin, Elizabeth M.; Kurtz, Theodore W.
In: Journal of Clinical Investigation, Vol. 103, No. 12, 06.1999, p. 1651-1657.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension
AU - Pravenec, Michal
AU - Zidek, Vaclav
AU - Simakova, Miroslava
AU - Kren, Vladimir
AU - Krenova, Drahomira
AU - Horky, Karel
AU - Jachymova, Marie
AU - Mikova, Blanka
AU - Kazdova, Ludmila
AU - Aitman, Timothy J.
AU - Churchill, Paul C.
AU - Webb, R. Clinton
AU - Hingarh, Nilesh H.
AU - Yang, Ying
AU - Wang, Jia Ming
AU - St. Lezin, Elizabeth M.
AU - Kurtz, Theodore W.
PY - 1999/6
Y1 - 1999/6
N2 - 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 Broom 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.
AB - 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 Broom 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.
UR - http://www.scopus.com/inward/record.url?scp=0032693236&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032693236&partnerID=8YFLogxK
U2 - 10.1172/JCI6691
DO - 10.1172/JCI6691
M3 - Article
C2 - 10377171
AN - SCOPUS:0032693236
VL - 103
SP - 1651
EP - 1657
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 12
ER -