1. Institute of Cytology and Genetics SB RAS 2. Institute of Internal Medicine SB RAMS 3. Institute of Molecular Biology and Biophysics, Siberian Branch of Russian Academy of Medical Sciences 4. Institute of Physiology SB RAMS 5. Novosibirsk State University
Abstract: It is known that the metabolic syndrome (MS), which includes hypertension, dislipidemia, glucose intolerance, and obesity leads to cardiovascular diseases. The MS risk is growing catastrophically. Molecular mechanisms allowing to understand the reason of integrated dysfunctions, taking place at MS cases, have remained almost unstudied. The chronical stress plays a crucial role in MS development; therefore in the present work a hypertensive rat strain with Inherited Stress-Induced Arterial Hypertension (ISIAH) was used as a model. It was shown that ISIAH rat strain as compared with the control WAG rat strain is characterized by increased content of triglyceride, VLDL and LDL cholesterols, a decreased content of HDL cholesterol, a high level of apolipoprotein B-100, and decreased level of apolipoprotein А-I. The ISIAH rats body weight was higher as compared with WAG rats; ISIAH rats blood glucose content was higher too. Thus, strain hypertension for ISIAH rat is accompanied by dislipidemia, increased glucose content, and increased body weight, representing a whole set of MS signs. Since at MS cases the systemic abnormalities in lipid and carbohydrate metabolism take place, the functional activity of transcription factors (TFs) participating in integral regulation of lipid and carbohydrate metabolism genes in liver was measured. PPAR, LXR, PXR, CAR DNA-binding activity was increased in ISIAH rats, suggesting involvement of these TFs in MS development. Integrated investigation of PPAR, LXR, PXR, CAR regulatory mechanisms, signal transduction and transcriptional targets will provide insights into the pathogenesis of MS and offer valuable information for designing of drugs for MS treatment.
Reference: Pivovarova Е.N., Dushkin М.I., Perepechaeva M.L., Kobzev V.F., Trufakin V.А., Mаrkel А.L., All signs of metabolic syndrome in the hypertensive ISIAH rats are associated with increased activity of transcription factors PPAR, LXR, PXR, and CAR in the liver, Biomeditsinskaya khimiya, 2011, vol:
24. Patsouris D., Mandard S., Voshol P.J., Escher P., Tan N.S., Havekes L.M., Koenig W., Marz W., Tafuri S., Wahli W., Muller M., Kersten S. (2004) J. Clin. Invest., 114, 94-103. CrossRef Scholar google search
29. Chawla A., Boisvert W.A., Lee C.H., Laffitte B.A., Barak Y., Joseph S.B., Liao D., Nagy L., Edwards P.A., Curtiss L.K., Evans R.M., Tontonoz P. (2001) Mol. Cell, 7, 161-171. CrossRef Scholar google search
30. Cao G., Liang Y., Broderick C.L., Oldham B.A., Beyer T.P., Schmidt R.J., Zhang Y., Stayrook K.R., Suen C., Otto K.A., Miller A.R., Dai J., Foxworthy P., Gao H., Ryan T.P., Jiang X.C., Burris T.P., Eacho P.I., Etgen G.J. (2003) J. Biol. Chem., 278, 1131-1136. CrossRef Scholar google search