P476SREBF1, SREBF2 and their target genes expression is different in wistar and SHR rats under high cholesterol treatment conditions

Abstract

Purpose: Investigate pathophysiological changes in cardiovascular system and discover the role of SREBP related system in this process under conditions of essential hypertension and high cholesterol diet in rats. Methods: 6 month old male Wistar rats and spontaneously hypertensive rats (SHR) were taken as the objects of research. They were fed with standard rodent's food enriched with 3% cholesterol for 8 weeks. Registration of cardiac function using pressure-volume conductance catheter, lipid profile measurements, histological examinations, reverse transcription and real-time PCR were performed. Results: After cholesterol diet, hemodynamic parameters worsened in Wistar rats, but in SHR rats no significant changes in these parameters were found. Lipids profile researches has shown 27% higher levels of HDL in SHR rats before and after high cholesterol diet, in contrast to Wistar. Histological researches revealed considerable changes in cardiac and aortic tissues morphology and histological parameters after cholesterol diet in SHR unlike the Wistar rats. Our study indicates that levels of SREBF and their target genes expression are significantly different in Wistar and SHR rats. We have firstly described that levels of SREBF1 and SREBF2 mRNA in heart are lower in SHR than in Wistar rats. After cholesterol diet expression of SREBF1 and SREBF2 was increased only in SHR, but not in Wistar. In liver, another interrelation was observed - significant response on high cholesterol diet appeared only in Wistar rats. Expression of SREBF1 and SREBF2 target genes (Insig-1, HMGCoAr) was not associated with changes of SREBF expression. Conclusions: We have identified two different reactions. The first is cardiac functions and lipid profile levels deterioration, and changes in SREBF mRNA expression, but without any histological changes in aorta tissues in healthy Wistar rats after 8 weeks of 3% cholesterol diet. The second is characterized with absence of significant changes in cardiac function, similar lipid profile levels alteration, quite different profile of SREBF mRNA expression, and histological changes typical to first stages of atherosclerosis. These results confirm our hypothesis that SREBP-related system is involved in cardiac failure development and is affected by high arterial pressure and high cholesterol diet. Therefore it is potential target for further investigations in cardiac failure development, especially complicated by metabolic syndrome disorders like lipid profile deterioration and arterial hypertension.