Does peroxisome proliferator-activated receptor-gamma (PPAR gamma) protect from hypertension directly through effects in the vasculature?
Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a ligand-activated transcription factor of the nuclear hormone receptor superfamily. Increasing evidence suggests that PPAR gamma is involved in the regulation of vascular function and blood pressure in addition to its well recognized role in metabolism. Thiazolidinediones, PPAR gamma agonists, lower blood pressure and have protective vascular effects through largely unknown mechanisms. In contrast, loss-of-function dominant-negative mutations in human PPAR gamma cause insulin resistance and severe early onset hypertension. Recent studies using genetically manipulated mouse models have begun to specifically address the importance of PPAR gamma in the vasculature. In this minireview, evidence for a protective role of PPAR gamma in the endothelium and vascular smooth muscle, derived largely from studies of genetically manipulated mice, will be discussed.
Department of Internal Medicine, Center on Functional Genomics of Hypertension, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242.
Pimonrat
P
Ketsawatsomkron
Department of Internal Medicine, Center on Functional Genomics of Hypertension, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242.
Christopher J
CJ
Pelham
Department of Internal Medicine, Center on Functional Genomics of Hypertension, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242.
Séverine
S
Groh
Department of Internal Medicine, Center on Functional Genomics of Hypertension, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242.
Henry L
HL
Keen
Department of Internal Medicine, Center on Functional Genomics of Hypertension, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242.
Frank M
FM
Faraci
Department of Internal Medicine, Center on Functional Genomics of Hypertension, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242. Electronic address: curt-sigmund@uiowa.edu.
Curt D
CD
Sigmund
D000818:Animals; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000378:metabolism*; D005799:Genes, Dominant; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D007333:Insulin Resistance; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009154:Mutation; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D045162:Thiazolidinediones / Q000494:pharmacology
D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione