title: Mechanical overload-induced apoptosis: a study in cultured neonatal ventricular myocytes and fibroblasts.
abstract: Apoptosis of cardiac myocytes has been implicated in cardiac dysfunction due to chronic hemodynamic overload. Reports on the role of apoptosis in the transition from hypertrophy to decompensated heart failure are not unequivocal. In this study we analysed the direct relationship between mechanical overload and induction of apoptosis in an in vitro model of cultured heart cells. Cyclic mechanical stretch was applied to cultured neonatal rat ventricular myocytes and fibroblasts. Several indicators of apoptosis were examined, such as morphological features, caspase-3 activity and DNA fragmentation. Mechanical strain did not induce any significant change in these parameters as compared to non-stretched myocytes or fibroblasts. However, administration of staurosporine, a known inducer of apoptosis, induced massive apoptosis in myocytes as well as fibroblasts. We conclude that this in vitro cell model system lacks a direct link between mechanical stretch and apoptosis. The three-dimensional structure-function relationship of myocardial tissue in the intact heart may elicit stretch-induced molecular signaling cascades in a much more complex way than in monolayer cultures of cardiac cells.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marion
authors.initials: M
authors.lastname: Persoon-Rothert
authors.forename: Karlien G C
authors.initials: KG
authors.lastname: van der Wees
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004587:Electrophoresis, Agar Gel; D006352:Heart Ventricles / Q000166:cytology*; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
chemical_list: D016895:Culture Media, Serum-Free