{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:12:01Z","timestamp":1791313921183,"version":"4.3.1"},"reference-count":41,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":3144,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:p>The cysteine protease cathepsin K has been implicated in pathogenesis of cardiovascular disease. We hypothesized that ablation of cathepsin K protects against obesity-associated cardiac dysfunction. Wild-type mice fed a high-fat diet exhibited elevated heart weight, enlarged cardiomyocytes, increased left ventricular wall thickness, and decreased fractional shortening. All these changes were reconciled in cathepsin K knockout mice. Cathepsin K knockout partly reversed the impaired cardiomyocyte contractility and dysregulated calcium handling associated with high-fat diet. Additionally, cathepsin K knockout alleviated whole-body glucose intolerance and improved insulin-stimulated Akt phosphorylation in high-fat diet\u2013fed mice. High-fat feeding increased the expression of cardiac hypertrophic proteins and apoptotic markers, which were inhibited by cathepsin K knockout. Furthermore, high-fat feeding resulted in cathepsin K release from lysosomes into the cytoplasm. In H9c2 myoblasts, silencing of cathepsin K inhibited palmitic acid\u2013induced release of cytochrome c from mitochondria and expression of proapoptotic signaling molecules. Collectively, our data indicate that cathepsin K contributes to the development of obesity-associated cardiac hypertrophy and may represent a potential target for the treatment to obesity-associated cardiac anomalies.<\/jats:p>","DOI":"10.2337\/db12-0350","type":"journal-article","created":{"date-parts":[[2012,10,17]],"date-time":"2012-10-17T01:09:20Z","timestamp":1350436160000},"page":"498-509","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":82,"title":["Cathepsin K Knockout Mitigates High-Fat Diet\u2013Induced Cardiac Hypertrophy and Contractile Dysfunction"],"prefix":"10.2337","volume":"62","author":[{"given":"Yinan","family":"Hua","sequence":"first","affiliation":[{"name":"Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy, College of Health Sciences, Laramie, Wyoming"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy, College of Health Sciences, Laramie, Wyoming"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Dolence","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy, College of Health Sciences, Laramie, Wyoming"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Ping","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ren","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy, College of Health Sciences, Laramie, Wyoming"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreejayan","family":"Nair","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy, College of Health Sciences, Laramie, Wyoming"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2013,1,17]]},"reference":[{"key":"2022031210543282900_B1","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.2337\/dc06-9911","article-title":"Preventing cardiovascular disease and diabetes: a call to action from the American Diabetes Association and the American Heart Association","volume":"29","author":"Eckel","year":"2006","journal-title":"Diabetes Care"},{"key":"2022031210543282900_B2","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1161\/CIRCULATIONAHA.106.171016","article-title":"Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism","volume":"113","author":"Poirier","year":"2006","journal-title":"Circulation"},{"key":"2022031210543282900_B3","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1161\/01.HYP.0000184282.51550.00","article-title":"Cardiovascular mortality in overweight subjects: the key role of associated risk factors","volume":"46","author":"Thomas","year":"2005","journal-title":"Hypertension"},{"key":"2022031210543282900_B4","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1001\/jama.1991.03470020057032","article-title":"The impact of obesity on left ventricular mass and geometry. 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