Cathepsin K-deficiency impairs mouse cardiac function after myocardial infarction
| Autor: | Yan Lin, Peter Libby, Meixiang Xiang, Cong-Lin Liu, Yajun Wang, Natasha Barascuk, Wenqian Fang, Galina K. Sukhova, Guo-Ping Shi, Aina He, Jie Li, Chongzhe Yang, Xian Zhang, Morten A. Karsdal, Lise Larsen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cardiac function curve Male Programmed cell death medicine.medical_specialty Heart Ventricles Cathepsin K Myocardial Infarction Apoptosis 030204 cardiovascular system & hematology Extracellular matrix 03 medical and health sciences Mice 0302 clinical medicine Fibrosis Internal medicine Medicine Animals Humans Myocardial infarction Acute Coronary Syndrome Ventricular remodeling Molecular Biology Aged Cell Proliferation Inflammation business.industry Middle Aged medicine.disease 030104 developmental biology Endocrinology Heart Function Tests Myocardial fibrosis Female Collagen Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of molecular and cellular cardiology. 127 |
| ISSN: | 1095-8584 |
| Popis: | Background Extracellular matrix metabolism and cardiac cell death participate centrally in myocardial infarction (MI). This study tested the roles of collagenolytic cathepsin K (CatK) in post-MI left ventricular remodeling. Methods and results Patients with acute MI had higher plasma CatK levels (20.49 ± 7.07 pmol/L, n = 26) than those in subjects with stable angina pectoris (8.34 ± 1.66 pmol/L, n = 28, P = .01) or those without coronary heart disease (6.63 ± 0.84 pmol/L, n = 93, P = .01). CatK protein expression increases in mouse hearts at 7 and 28 days post-MI. Immunofluorescent staining localized CatK expression in cardiomyocytes, endothelial cells, fibroblasts, macrophages, and CD4+ T cells in infarcted mouse hearts at 7 days post-MI. To probe the direct participation of CatK in MI, we produced experimental MI in CatK-deficient mice (Ctsk−/−) and their wild-type (Ctsk+/+) littermates. CatK-deficiency yielded worsened cardiac function at 7 and 28 days post-MI, compared to Ctsk+/+ littermates (fractional shortening percentage: 5.01 ± 0.68 vs. 8.62 ± 1.04, P Conclusion Plasma CatK levels are increased in MI patients. Heart CatK expression is also elevated post-MI, but CatK-deficiency impairs post-MI cardiac function in mice by increasing myocardial fibrosis and cardiomyocyte death. |
| Databáze: | OpenAIRE |
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