Regulatory mechanisms of atrial fibrotic remodeling in atrial fibrillation.
Electrical, contractile and structural remodeling have been characterized in atrial fibrillation (AF), and the latter is considered to be the major contributor to AF persistence. Recent data show that interstitial fibrosis can predispose to atrial conduction impairment and AF induction. The interplay between cardiac matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs), is thought to be critical in atrial extracellular matrix (ECM) metabolism. At the molecular level, angiotensin II, transforming growth factor-beta1, inflammation and oxidative stress are particularly important for ECM dysregulation and atrial fibrotic remodeling in AF. Therefore, we review recent advances in the understanding of the atrial fibrotic process, the major downstream components in this remodeling process, and the expression and regulation of MMPs and TIMPs. We also describe the activation of bioactive molecules in both clinical studies and animal models to modulate MMPs and TIMPs and their effects on atrial fibrosis in AF.
Lin
C-S
CS
Department of Biological Science and Technology, National Chiao Tung University, No. 75 Po-Ai Street, Hsinchu, Taiwan. lincs@mail.nctu.edu.tw
Pan
C-H
CH
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000235:genetics / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000235:genetics / Q000503:physiopathology*; D004719:Endomyocardial Fibrosis / Q000235:genetics / Q000503:physiopathology*; D006325:Heart Atria / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D020257:Ventricular Remodeling / Q000235:genetics*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; D020703:ras GTPase-Activating Proteins; D000804:Angiotensin II; D000803:Angiotensin I; D020782:Matrix Metalloproteinases; C118790:angiotensin I (1-7)