All signs of the metabolic syndrome in hypertensive ISIAH rats are associated with increased activity of the transcription factors PPAR, LXR, PXR, and CAR in the liver

It is known that the metabolic syndrome (MS) characterized by hypertension, dyslipidemia, glucose tolerance, and obesity leads to serious cardiovascular diseases, which still are the leading cause of mortality in developed countries. The MS distribution is growing catastrophically, but molecular mechanisms responsible for developments of complex impairments in MS still remain basically poorly investigated. Since the chronic stress plays a crucial role in MS development, in the present work a hypertensive rat strain with Inherited Stress-Induced Arterial Hypertension (ISIAH-strain) was used as a model. It was shown that the ISIAH rat strain is characterized by an increased content of triglyceride, VLDL and LDL cholesterols, a decreased content of HDL cholesterol, a high level of apolipoprotein B-100, and a decreased level of apolipoprotein A-I as compared with the control WAG rat strain. The ISIAH rat body weight and blood glucose level were higher than in WAG rats. Thus, hypertension in ISIAH rats is accompanied by dislipidemia, increased glucose level, and increased body weight, representing a whole set of symptoms typical for MS. The DNA-binding activity of the transcription factors involved into regulation of lipid and carbohydrate metabolism genes (PPAR, LXR, PXR, and CAR) was higher in ISIAH rats compared with WAG rats. A complex study of regulatory mechanisms, signaling pathways, and transcription targets mediating PPAR, LXR, PXR, and CAR effects may help better understanding of the MS pathogenesis and provide valuable information for design of complex drugs for MS treatment.