Peroxisome proliferator-activated receptor (PPAR)-α is a connecting link between cardiac fibrosis and oxidative stress in atrial fibrillation
Recommended Citation
Rizvi F, Emelyanova L, Edwards S, et al. Peroxisome proliferator-activated receptor (PPAR)-α is a connecting link between cardiac fibrosis and oxidative stress in atrial fibrillation. Poster presented at: Basic Cardiovascular Sciences 2017 Scientific Sessions; July 10-13, 2017; Portland, Oregon.
Presentation Notes
Poster presented at: Basic Cardiovascular Sciences 2017 Scientific Sessions; July 10-13, 2017; Portland, Oregon.
Abstract
Background: AF, a common sustained arrhythmia that predisposes heart failure and stroke, is associated with cardiac fibrosis and oxidative stress. Peroxisome proliferator-activated receptor (PPAR)- α, important for ROS and lipid degradation, is reported to negatively correlate with kidney, liver, and lung fibrosis, but its role in cardiac fibrosis is less clear. We hypothesize that reduced expression of PPARα in AF contributes to oxidative stress and interferes with TGFβ signaling, a cytokine implicated in cardiac fibrosis.
Methods: Myocardial fibrosis was detected (Masson trichrome) in right atrial appendages of AF and nonAF patients. Levels of 4-hydroxynonenal (4-HNE) (ELISA) and superoxide production (MitoSOX) were assayed in patients’ atrial tissue homogenates and cardiac myofibers respectively. Using atrial fibroblasts (hAF) from AF and non-AF patients, α-SMA, COL1A1 and c-Jun/c-Fos expressions were determined (RTPCR and/or Western Blot) in the absence and presence of TGF-β (5 ng) with or without ciprofibrate (200 µM), a PPARα agonist.
Results:Increased atrial fibrosis, levels of 4-HNE (101.7 vs 7.4 ng/mg protein; p=0.02(n=6)) and oxidative stress (8.7 fold; p=0.04) correlated with reduced PPAR-α mRNA (2.1 fold; p
Conclusion: Reduced expression of PPARα is associated with impaired cardiac mitochondrial metabolism and promotes TGFβ-induced profibrotic pathway. Preliminary data suggest PPARα agonist might confer therapeutic benefits for patients with cardiac fibrosis and oxidative stress in AF.
Document Type
Poster
Affiliations
Ctr for Integrative Res on Cardiovascular Aging (CIRCA)
Aurora UW Medical Group
Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Ctrs