Abstract 8269: Cysteine Protease Cathepsin K: A New Biomarker in Patients with Atrial Fibrillation

Abstract

Background. The cysteine protease cathepsin K is one of the most potent mammalian collagenases and elastases. It is overexpressed in cardiovascular tissues in response to injury, and is regulated by pro-inflammatory stimuli. Atrial remodeling in atrial fibrillation (AF) involves extensive extracellular matrix (ECM) remodeling that requires collagenolysis and elastolysis. We hypothesized that plasma levels of cathepsin K could be an important biomarker for atrial remodeling in AF patients receiving ablation therapy. Methods and Results. We examined a total of 156 subjects with paroxysmal AF (PAF) and 67 with chronic AF (CAF), as well as 21 individuals free from atrial disease. Plasma cathepsin K, interleukin-1β (IL-1β), high-sensitivity C-reactive protein (CRP), intact amino-terminal peptide of procollagen type I (I-PINP, as a marker of collagen type I synthesis), carboxyl-terminal telopeptide of collagen type I (ICTP, as a marker of collagen type I degradation), and lipid protein profiles were measured. Serum cathepsin K levels were significantly higher in patients with AF than in those without AF (AF vs. non-AF: 20.8 ± 3.5 ng/mL vs. 6.1 ± 0.8 ng/mL, P < 0.01). Patients with AF had higher levels of IL-1β, CRP, and ICTP than those without AF ( P < 0.05). After subgrouping the AF patients into those with PAF or CAF, we found that patients with CAF had higher levels of cathepsin K and IL-1β than those with PAF ( P < 0.05). Although a Spearman's correlation test showed that plasma cathepsin K correlated significantly with IL-1β ( P < 0.01), ICTP ( P < 0.05) and left atrial diameter ( P < 0.05), and correlated weakly with I-PINP ( P = 0.08), serum cathepsin K levels remained significantly higher in AF patients than in non-AF patients in a multiple linear regression test after adjusting for all of these confounders (P < 0.01). Conclusions. Our findings suggest that circulating cathepsin K represents a novel potential marker of atrial remodeling and therapeutic efficacy and that augmented cathepsin K, IL-1β, and ICTP levels could provide an underlying inflammation-induced proteolytic mechanism of atrial remodeling in cases of AF.