| First Author | Hua Y | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 2 | Pages | 498-509 |
| PubMed ID | 23069627 | Mgi Jnum | J:208613 |
| Mgi Id | MGI:5563763 | Doi | 10.2337/db12-0350 |
| Citation | Hua Y, et al. (2013) Cathepsin K knockout mitigates high-fat diet-induced cardiac hypertrophy and contractile dysfunction. Diabetes 62(2):498-509 |
| abstractText | 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-fed 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-induced 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. |
