Hypertension induced microRNA changes in the rat heart

Tilde Eskildsen (Foredragsholder)

Aktivitet: Foredrag og mundtlige bidragForedrag og præsentationer i privat eller offentlig virksomhed


Tilde Eskildsen(1), AY Nossent(0), M Schneider(2), D Andersen(2), M Sandberg(2), H Jensen(1), P Jeppesen(1), B Jensen(1), P Bie(1), S Sheikh(2)

Cardiac remodeling, characterized by left ventricular hypertrophy and increased fibrosis, is a detrimental consequence of Angiotensin II (AngII) induced hypertension, leading to impaired heart performance and reduced life expectancy. As recent studies suggest that dysregulated microRNAs (miRNAs) are involved in these cardiac disease processes, we set out to identify miRNAs directly induced by AngII. Hypertension was induced in rats by continuous intravenous AngII infusion administered for 4 hours or 10 days to study acute and long-term effects, respectively. Using this model, we found a 60 mmHg elevation in the blood pressure and a 21% increase in left ventricle mass in chronically affected rats as compared to controls confirming hypertension and cardiac hypertrophy. Differentially expressed miRNAs was assessed by microarray and confirmed by RT-qPCR. RT-qPCR revealed the same tendency in acute rats as observed in chronic rats indicating a direct induction by AngII. Relevant differentially expressed miRNAs were confirmed in vitro by AngII stimulation of rat cardiac fibroblasts and manipulation in vitro by anti-miR or pre-miR transfection is being performed. The ability of the anti- and pre-miRNAs to modulate AngII induced fibroblasts activation is being evaluated by measuring cell proliferation and size and by RT-qPCR and immunocytochemistry for hypertrophic and fibroblastic markers. In this study we have identified a number of AngII induced miRNAs, which potentially play a role in AngII induced cardiac hypertrophy and fibrosis. We speculate that by targeting those miRNAs, the onset and long-term progression of cardiac hypertrophy and fibrosis can be substantially reduced.

Periode19. jul. 2010
BegivenhedstitelWorld Congress of Basic and Clinical Parmacology: null
PlaceringCopenhagen, Danmark