title: Selective induction of matrix metalloproteinases and tissue inhibitor of metalloproteinases in atrial and ventricular myocardium in patients with atrial fibrillation.
abstract: Atrial fibrillation (AF) produces changes in atrial structure and extracellular matrix composition, which is regulated by matrix metalloproteinases (MMPs). Moreover, AF often occurs in the setting of congestive heart failure (CHF), which also affects MMPs. Whether changes in MMPs or the tissue inhibitors of metalloproteinases (TIMPs) within atrial and ventricular myocardium are differentially regulated with AF remains unclear. Myocardium from the walls of the right atrium, right ventricle, left atrium, and left ventricle was obtained from the explanted hearts of 43 patients with end-stage CHF. AF was present in 23 patients (duration 1 to 84 months). The remaining 20 patients served as non-AF controls. The groups were well matched clinically, but left atrial (LA) size was increased in the AF cohort (5.5 +/- 0.8 vs 4.9 +/- 0.7 cm, p <0.05). Myocardial collagen content and levels of MMP-1, -2, -8, -9, -13, and -14, and TIMP-1, -2, -3, and TIMP-4 were determined. With AF, collagen content was greater within the atrial myocardium but less in the ventricular myocardium. There were chamber-specific differences in MMPs and TIMPs with AF. For example, MMP-1 in the right atrium and MMP-9 in the left atrium were greater with AF. TIMP-3 levels were greater in the right ventricle, left atrium, and left ventricle. Although total LA collagen was positively correlated with AF duration (r = 0.49, p <0.03), there was an inverse relation between soluble collagen I and AF duration (n = 6, r = -0.84, p <0.04). In conclusion, AF is associated with chamber-specific alterations in myocardial collagen content and MMP and TIMP levels, indicative of differential remodeling and altered collagen metabolism. Differences in MMP and TIMP profiles may provide diagnostic and mechanistic insights into the pathogenesis of AF with CHF.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA. mukherr@musc.edu
authors.forename: Rupak
authors.initials: R
authors.lastname: Mukherjee
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Herron
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Lowry
authors.forename: Robert E
authors.initials: RE
authors.lastname: Stroud
authors.forename: Martha R
authors.initials: MR
authors.lastname: Stroud
authors.forename: J Marcus
authors.initials: JM
authors.lastname: Wharton
authors.forename: John S
authors.initials: JS
authors.lastname: Ikonomidis
authors.forename: A Jackson
authors.initials: AJ
authors.lastname: Crumbley
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gold
mesh_terms: D000328:Adult; D001281:Atrial Fibrillation / Q000378:metabolism*; D003094:Collagen / Q000032:analysis; D004790:Enzyme Induction; D006325:Heart Atria / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases