Journal
BASIC RESEARCH IN CARDIOLOGY
Volume 107, Issue 5, Pages -Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-012-0278-0
Keywords
Atrial fibrosis; Atrial fibrillation; MicroRNA; miR-21; Lysyl oxidase
Categories
Funding
- Deutsche Forschungsgemeinschaft [KFO 196]
- Universitat des Saarlandes
- European Stroke Network (ESN)
- Ministerium fur Wirtschaft und Wissenschaft des Saarlandes
Ask authors/readers for more resources
Atrial fibrosis is important for the pathogenesis of atrial fibrillation (AF) but the underlying signal transduction is incompletely understood. We therefore studied the role of microRNA-21 (miR-21) and its downstream target Sprouty 1 (Spry1) during atrial fibrillation. Left atria (LA) from patients with AF showed a 2.5-fold increased expression of miR-21 compared to matched LA of patients in sinus rhythm. Increased miR-21 expression correlated positively with atrial collagen content and was associated with a reduced protein expression of Spry1 and increased expression of connective tissue growth factor (CTGF), lysyl oxidase and Rac1-GTPase. Neonatal cardiac fibroblasts treated with angiotensin II (AngII) or CTGF showed an increased miR-21 and decreased Spry1 expression. Pretreatment with an inhibitor of Rac1 GTPase, NSC23766, reduced the AngII-induced upregulation of miR-21. A small molecule inhibitor of lysyl oxidase, BAPN, prevented the AngII as well as the CTGF-induced miR-21 expression. Transgenic mice with cardiac overexpression of Rac1, which develop spontaneous AF and atrial fibrosis with increasing age, showed upregulation of miR-21 expression associated with reduced Spry1 expression. miR-21 expression and signalling in vivo were prevented by long-term treatment of the mice with statins. Direct inhibition of miR-21 by antagomir-21 prevented fibrosis of the atrial myocardium post-myocardial infarction. Left atria of patients with atrial fibrillation are characterized by upregulation of miR-21 und reduced expression of Spry1. Activation of Rac1 by angiotensin II leads to a CTGF-and lysyl oxidase-mediated increase of miR-21 expression contributing to structural remodelling of the atrial myocardium.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available