title: Transforming growth factor-beta1 downregulates beating frequency and remodeling of cultured rat adult cardiomyocytes.
abstract: We have observed increased levels of transforming growth factor-beta1 (TGF-beta1) in human hibernating myocardium (HM). Impaired ventricular function in HM is known to be restored to normal following revascularization implying that myocardial structure in HM is to a certain degree preserved. We have therefore tested whether TGF-beta1 can imitate features of HM by reducing the number and frequency of beating cells (chronotropism) and structural remodeling of cultured adult rat cardiomyocytes (ARC), thus saving substrate, energy, and oxygen. Parameters measured were cell size, protein synthesis, protein degradation, protein content, myofibrillogenesis, and chronotropism. ARC were stimulated for 6 days with sera from patients with coronary heart disease, as this period led to a maximum response of cells. An increase of 90% in cell surface area following such treatment was reduced to a 20% increase of the original size by TGF-beta1. Concomitantly, the rate of protein synthesis dropped from 3.6-fold to 2.4-fold, and myofibrillogenesis was reduced. TGF-beta1 downregulated both the number of contracting cells from 81% to 10% and the frequency from 52 to nine beats per minute. However, TGF-beta1 treatment did not reduce the augmentation of protein content (1.28-fold versus 1.25-fold) indicating that protein degradation was also inhibited. Similar results were obtained with serum from healthy volunteers. The effects of TGF-beta1 were reversible. We conclude that TGF-beta1 constrains protein turnover and beating activity in underperfused myocardium, thus mediating protection by adapting myocytes to shortages in blood supply.
authors.affiliation: Research Group Vascular Genomics, Kerckhoff Clinic, Bad Nauheim, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kubin
authors.forename: Maren
authors.initials: M
authors.lastname: Tomars
authors.forename: Christian
authors.initials: C
authors.lastname: Fach
authors.forename: Stefan
authors.initials: S
authors.lastname: Hein
authors.forename: Peter
authors.initials: P
authors.lastname: Bramlage
authors.forename: Gil-Jin
authors.initials: GJ
authors.lastname: Shim
authors.forename: Dimitri
authors.initials: D
authors.lastname: Scholz
authors.forename: Sawa
authors.initials: S
authors.lastname: Kostin
authors.forename: René
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Albrecht
authors.initials: A
authors.lastname: Elsässer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaper
authors.forename: Jutta
authors.initials: J
authors.lastname: Schaper
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D049108:Cell Enlargement / Q000187:drug effects; D048429:Cell Size; D002478:Cells, Cultured; D003327:Coronary Disease / Q000503:physiopathology; D003470:Culture Media / Q000737:chemistry; D016895:Culture Media, Serum-Free; D015536:Down-Regulation; D005260:Female; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008857:Microscopy, Interference; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044967:Serum / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
chemical_list: D003470:Culture Media; D016895:Culture Media, Serum-Free; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1