Mechanisms With Clinical Implications for Atrial Fibrillation–Associated Remodeling: Cathepsin K Expression, Regulation, and Therapeutic Target and Biomarker

DSpace/Manakin Repository

Mechanisms With Clinical Implications for Atrial Fibrillation–Associated Remodeling: Cathepsin K Expression, Regulation, and Therapeutic Target and Biomarker

Citable link to this page

 

 
Title: Mechanisms With Clinical Implications for Atrial Fibrillation–Associated Remodeling: Cathepsin K Expression, Regulation, and Therapeutic Target and Biomarker
Author: Fujita, Masaya; Cheng, Xian Wu; Inden, Yasuya; Shimano, Masayuki; Yoshida, Naoki; Inoue, Aiko; Yamamoto, Toshihiko; Takeshita, Kyosuke; Kyo, Seifuku; Taguchi, Noriko; Shi, Guo‐Ping; Kuzuya, Masafumi; Okumura, Kenji; Murohara, Toyoaki

Note: Order does not necessarily reflect citation order of authors.

Citation: Fujita, M., X. W. Cheng, Y. Inden, M. Shimano, N. Yoshida, A. Inoue, T. Yamamoto, et al. 2013. “Mechanisms With Clinical Implications for Atrial Fibrillation–Associated Remodeling: Cathepsin K Expression, Regulation, and Therapeutic Target and Biomarker.” Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 2 (6): e000503. doi:10.1161/JAHA.113.000503. http://dx.doi.org/10.1161/JAHA.113.000503.
Full Text & Related Files:
Abstract: Background: The cysteine protease cathepsin K (CatK) has been implicated in the pathogenesis of cardiovascular disease. We sought to determine the link between atrial fibrillation (AF) and plasma CatK levels and to investigate the expression of and therapeutic target for CatK in vivo and in vitro. Methods and Results: Plasma CatK and extracellular matrix protein peptides (intact procollagen type I of N‐terminal propeptide; carboxyl‐terminal telopeptide of type I collagen [ICTP]) were measured in 209 consecutive patients with AF (paroxysmal AF, 146; persistent AF, 63) and 112 control subjects. In addition, the regulation of CatK expression was investigated in vivo and vitro. Patients with AF had higher plasma CatK and ICTP levels than did control subjects. Patients with persistent AF had higher levels of plasma CatK and ICTP than did patients with paroxysmal AF. CatK was correlated with ICTP concentration and left atrial diameter in all subjects. In rabbits, superoxide production, CatK activity, fibrosis, and the levels of atrial tissue angiotensin II, angiotensin type 1 receptor, gp91phox, phospho‐p38 mitogen‐activated protein kinase, and CatK were greater in those with tachypacing‐induced AF than in controls, and these changes were reversed with angiotensin type 1 receptor antagonist. Olmesartan and mitogen‐activated protein kinase inhibitor decreased the CatK expression induced by angiotensin II in rat neonatal myocytes. Conclusions: These data indicated that increased plasma CatK levels are linked with the presence of AF. Angiotensin type 1 receptor antagonist appears to be effective in alleviating atrial fibrosis in a rabbit AF model, partly reducing angiotensin type 1 receptor‐p38mitogen‐activated protein kinase‐dependent and ‐independent CatK activation, thus preventing AF.
Published Version: doi:10.1161/JAHA.113.000503
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886768/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879591
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters