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.
Pravenec
M
M
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague. pravenec@biomed.cas.cz
Zídek
V
V
Landa
V
V
Kostka
V
V
Musilová
A
A
Kazdová
L
L
Fucíková
A
A
Krenová
D
D
Bíla
V
V
Kren
V
V
D000818:Animals; D020296:Animals, Congenic; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000235:genetics; D018955:CD36 Antigens / Q000235:genetics* / Q000502:physiology; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D004040:Dietary Carbohydrates / Q000493:pharmacokinetics; D004041:Dietary Fats / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D017353:Gene Deletion; D005816:Genetic Complementation Test; D008040:Genetic Linkage; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology / Q000235:genetics; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D007668:Kidney / Q000503:physiopathology; D008066:Lipolysis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D019655:Quantitative Trait, Heritable; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion; D014178:Translocation, Genetic / Q000235:genetics
D018955:CD36 Antigens; D018076:DNA, Complementary; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005227:Fatty Acids