Abstract 15690: Statins as Potential Farnesoid X Receptor Modulators in Atrial Cardiomyocytes: A Gender, Age and miR328 Controlled Response
Farnesoid X receptor (FXR) plays an important role in lipid and glucose metabolism and statins are known negative regulators of FXR expression. The role of FXR in atrial fibrillation (AF) has not been defined. MicroRNA-328 (miR-328) a small non-coding RNA contributes to adverse electrical remodeling in AF a common complication after coronary artery bypass grafting (CABG). The present study aimed to examine the levels of FXR mRNA and miR328 in 30 consecutive patients undergoing CABG. The patients group was made up of 10 women and 20 men with a mean +/-SEM. age of 68.5+/-2.1 and 64.3+/-2.3 years respectively, 14 of them on statin therapy. We analyzed right atrial biopsies taken pre aortic occlusion and post reperfusion.
Post reperfusion, mean (S.E.) FXR mRNA levels increased 3.41+/-1.07 fold (p<0.05) and mean (S.E.) miR-328 levels decreased 0.61+/-0.15 fold relative to pre aortic occlusion. We assessed miR-328 expression in human tissue to confirm its potential relevance to human FXR cardiac gene regulation and adjusted the results for the combined confounding effect of age, gender and statin therapy. The linear model described showed a significant relationship of all the above predictors to FXR mRNA levels (p=0.004). On average and holding everything else fixed FXR mRNA post-pre CABG in patients under statin therapy were -2.6 units lower (95% C.I.-4.43,-0.80) than in patients not taking statins (p=0.007). Each additional year of age results in FXR mRNA being 0.27 units higher (95% C.I. 0.04, 0.48) (p=0.018). Female patient FXR mRNA was 2.10 units higher (95% C.I. 0.12, 4,09) than their male counterparts (p=0.039). miR-328 post-pre CABG (after log transformation for normality) showed an inverse relation (p=0.035) with FXR mRNA, specifically for every unit increase of miR-328 a 16 unit decrease of FXR mRNA levels occurred (95% C.I. -30.96, -1.28). These results suggest that FXR regulation during CABG is dependent on statin therapy, is gender specific and increases with age. Also the inverse relation of FXR mRNA with miR-328 suggests a possible interplay between metabolic and electrical substrate alterations for the atrial myocardium during CABG.
Author Disclosures: V. Salpeas: None. J. Tsoporis: None. S. Izhar: None. E. Sakadakis: None. A.G. Rigopoulos: None. T.G. Parker: None. I.K. Rizos: None.
- © 2014 by American Heart Association, Inc.