Transcriptomic analysis of left ventricle myocardium in an SHR congenic line with ameliorated cardiac fibrosis.

Abstract

Metabolic syndrome and one of its manifestations, essential hypertension, is an important cause of worldwide morbidity and mortality. Morbidity and mortality associated with hypertension are caused by organ complications. Previously we revealed a decrease of blood pressure and an amelioration of cardiac fibrosis in a congenic line of spontaneously hypertensive rats (SHR), in which a short segment of chromosome 8 (encompassing only 7 genes) was exchanged for a segment of normotensive polydactylous (PD) origin. To unravel the genetic background of this phenotype we compared heart transcriptomes between SHR rat males and this chromosome 8 minimal congenic line (PD5). We found 18 differentially expressed genes, which were further analyzed using annotations from Database for Annotation, Visualization and Integrated Discovery (DAVID). Four of the differentially expressed genes (Per1, Nr4a1, Nr4a3, Kcna5) belong to circadian rhythm pathways, aldosterone synthesis and secretion, PI3K-Akt signaling pathway and potassium homeostasis. We were also able to confirm Nr4a1 2.8x-fold upregulation in PD5 on protein level using Western blotting, thus suggesting a possible role of Nr4a1 in pathogenesis of the metabolic syndrome.