Published Online
on March 5, 2007

A more recent version of this article appeared on May 1, 2007

This Article Full Text (PDF) All Versions of this Article: 49/5/941    most recent HYPERTENSIONAHA.107.086900v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pravenec, M. Articles by Kurtz, T. W. Search for Related Content PubMed PubMed Citation Articles by Pravenec, M. Articles by Kurtz, T. W. Pubmed/NCBI databases Medline Plus Health Information High Blood Pressure Metabolic Syndrome Related Collections Animal models of human disease Functional genomics Hypertension - basic studies Type 2 diabetes Glucose intolerance Genetics of cardiovascular disease

Submitted on January 2, 2007
Revised on January 27, 2007

Molecular Genetics of Experimental Hypertension and the Metabolic Syndrome. From Gene Pathways to New Therapies

Michal Pravenec and Theodore W. Kurtz^*

From the Institute of Physiology and Center for Applied Genomics (M.P.), Czech Academy of Sciences, Prague, Czech Republic; and the Department of Laboratory Medicine (T.W.K.), University of California San Francisco.

^* To whom correspondence should be addressed. E-mail: KurtzT{at}Labmed2.ucsf.edu.

Abstract--Genetic studies of human and experimental hypertension provide a means to identify key pathways that predispose individuals to increased blood pressure and associated risk factors for cardiovascular and metabolic diseases. The pathways so identified can then serve as targets for therapeutic intervention. This article discusses genetic studies in animal models of hypertension in which specific genes have been identified that regulate blood pressure and biochemical features of the metabolic syndrome. Consistent with studies in humans with monogenic disorders of blood pressure regulation, studies in rat models have demonstrated that naturally occurring genetic variation in pathways regulating sodium chloride transport can contribute to inherited variation in blood pressure. Such studies have also indicated that naturally occurring variation in genes, such as Cd36, that regulate fatty acid metabolism and ectopic accumulation of fat and fat metabolites can influence both biochemical and hemodynamic features of the metabolic syndrome and mediate the antidiabetic effects of drugs that activate the peroxisome proliferator-activated receptor-. Angiotensin II receptor blockers with the ability to selectively modulate activity of peroxisome proliferator-activated receptor- and expression of genes in these fat metabolism pathways may represent useful prototypes for a new class of transcription modulating drugs aimed at treating patients with hypertension and the metabolic syndrome.

Key words: genetics • rats • inbred SHR • metabolic syndrome X • hypertension • angiotensin II type 1 receptor blockers • peroxisome proliferator-activated receptors

This article has been cited by other articles:

				M. Feng, M. E. Deerhake, R. Keating, J. Thaisz, L. Xu, S.-W. Tsaih, R. Smith, T. Ishige, F. Sugiyama, G. A. Churchill, et al. Genetic Analysis of Blood Pressure in 8 Mouse Intercross Populations Hypertension, October 1, 2009; 54(4): 802 - 809. [Abstract] [Full Text] [PDF]

				E. Samuelson, C. Hedberg, S. Nilsson, and A. Behboudi Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats Endocr. Relat. Cancer, March 1, 2009; 16(1): 99 - 111. [Abstract] [Full Text] [PDF]

				X. Jin, T. S. Ha, and D. P. Smith SNMP is a signaling component required for pheromone sensitivity in Drosophila PNAS, August 5, 2008; 105(31): 10996 - 11001. [Abstract] [Full Text] [PDF]

				L. Love-Gregory, R. Sherva, L. Sun, J. Wasson, T. Schappe, A. Doria, D.C. Rao, S. C. Hunt, S. Klein, R. J. Neuman, et al. Variants in the CD36 gene associate with the metabolic syndrome and high-density lipoprotein cholesterol Hum. Mol. Genet., June 1, 2008; 17(11): 1695 - 1704. [Abstract] [Full Text] [PDF]

				M. Pravenec, L. Kazdova, V. Landa, V. Zidek, P. Mlejnek, M. Simakova, P. Jansa, J. Forejt, V. Kren, D. Krenova, et al. Identification of Mutated Srebf1 as a QTL Influencing Risk for Hepatic Steatosis in the Spontaneously Hypertensive Rat Hypertension, January 1, 2008; 51(1): 148 - 153. [Abstract] [Full Text] [PDF]

				N. H. Lee, B. J. Haas, N. E. Letwin, B. C. Frank, T. V. Luu, Q. Sun, C. D. House, S. Yerga-Woolwine, P. Farms, E. Manickavasagam, et al. Cross-Talk of Expression Quantitative Trait Loci Within 2 Interacting Blood Pressure Quantitative Trait Loci Hypertension, December 1, 2007; 50(6): 1126 - 1133. [Abstract] [Full Text] [PDF]

				Y. Saad, S. Yerga-Woolwine, J. Saikumar, P. Farms, E. Manickavasagam, E. J. Toland, and B. Joe Congenic Interval Mapping of RNO10 Reveals a Complex Cluster of Closely-Linked Genetic Determinants of Blood Pressure Hypertension, November 1, 2007; 50(5): 891 - 898. [Abstract] [Full Text] [PDF]

				S. Sookoian and C. J. Pirola Review: Genetics of the cardiometabolic syndrome: new insights and therapeutic implications Therapeutic Advances in Cardiovascular Disease, October 1, 2007; 1(1): 37 - 47. [Abstract] [PDF]

				H. Hitomi, H. Kiyomoto, A. Nishiyama, T. Hara, K. Moriwaki, K. Kaifu, G. Ihara, Y. Fujita, T. Ugawa, and M. Kohno Aldosterone Suppresses Insulin Signaling Via the Downregulation of Insulin Receptor Substrate-1 in Vascular Smooth Muscle Cells Hypertension, October 1, 2007; 50(4): 750 - 755. [Abstract] [Full Text] [PDF]

				L. F. Lien, A. J. Brown, J. D. Ard, C. Loria, T. P. Erlinger, A. C. Feldstein, P.-H. Lin, C. M. Champagne, A. C. King, H. L. McGuire, et al. Effects of PREMIER Lifestyle Modifications on Participants With and Without the Metabolic Syndrome Hypertension, October 1, 2007; 50(4): 609 - 616. [Abstract] [Full Text] [PDF]