Essential Role for Premature Senescence of Myofibroblasts in Myocardial Fibrosis

• Published in: Journal of the American College of Cardiology Vol. 67; no. 17; pp. 2018 - 2028
• Main Authors: Meyer, Kathleen, Hodwin, Bettina, Ramanujam, Deepak, Engelhardt, Stefan, Sarikas, Antonio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.05.2016; Elsevier Limited
• Subjects: Actins - metabolism; Animals; antifibrotic therapy; beta-Galactosidase - metabolism; Biopsy; cardiac fibroblasts; Cardiology; Cardiovascular; Cell cycle; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cyclin-dependent kinases; Cysteine-Rich Protein 61 - metabolism; Deoxyribonucleic acid; Dependovirus - genetics; DNA; Enzymes; extracellular matrix; Fibroblasts; Fibrosis; gene therapy; Gene Transfer Techniques; Heart; Humans; Mice, Knockout; Myocardium - metabolism; Myocardium - pathology; Myofibroblasts - pathology; Proteins; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Rodents; Senescence; Statistical analysis; Studies; Surgery; transverse aortic constriction; Tumor Suppressor Protein p53 - deficiency; Vimentin - metabolism; Wound healing; antifibrotic therapy; CF; cardiac fibroblasts; gene therapy; CM; DN; ECM; RB; TG; TAC; transverse aortic constriction; SA-ß-gal; AAV9; WT; extracellular matrix; senescence-associated ß-galactosidase; adeno-associated virus serotype 9; retinoblastoma; dominant-negative; cardiomyocyte; transgenic; wild type

Fibrosis is a hallmark of many myocardial pathologies and contributes to distorted organ architecture and function. Recent studies have identified premature senescence as a regulatory mechanism of tissue fibrosis, but its relevance in the heart remains to be established. This study investigated the...