title: Affixin (β-parvin) promotes cardioprotective signaling via STAT3 activation.
abstract: The focal adhesion protein affixin (β-parvin) is highly expressed in the heart and is associated with the sarcomeric z-disc as well as the cell membrane. While affixin is known to be involved in cell adhesion and migration, its functional role in cardiomyocytes remains unclear. To gain insight into the function of affixin, we performed a yeast-two-hybrid-screen employing affixin as a bait. The signal transducer and activator of transcription 3 (STAT3) was detected as a binding partner of affixin. Overexpression of affixin in neonatal rat cardiomyocytes resulted in markedly enhanced STAT3 DNA binding activity and upregulation of STAT3-dependent genes. Moreover, upregulation of affixin led to cardiomyocyte hypertrophy with an increase in cell size and enhanced protein synthesis. Consistent with STAT3 activation, overexpression of affixin also protected cardiomyocytes from doxorubicin-induced apoptosis. Finally, HUVECs that were cultivated in medium from affixin-overexpressing cardiomyocytes responded with an increase in tubuli formation, in line with a proangiogenic effect of affixin. In conclusion, we demonstrate that affixin activates STAT3 in cardiomyocytes and promotes characteristic STAT3-related effects such as hypertrophy, protection against apoptosis, and angiogenesis. This novel pathway might therefore represent a target for cardioprotective strategies.
authors.affiliation: Department of Internal Medicine III, Cardiology and Angiology, University of Kiel, 24105 Kiel, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Luedde
authors.forename: Saskia
authors.initials: S
authors.lastname: Spaich
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Hippe
authors.forename: Sebastian
authors.initials: S
authors.lastname: Busch
authors.forename: Rainer
authors.initials: R
authors.lastname: Will
authors.forename: Issam
authors.initials: I
authors.lastname: Abu-Taha
authors.forename: Tilman
authors.initials: T
authors.lastname: Klein
authors.forename: Christian
authors.initials: C
authors.lastname: Kuhn
authors.forename: Derk
authors.initials: D
authors.lastname: Frank
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Norbert
authors.initials: N
authors.lastname: Frey
mesh_terms: D000185:Actinin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: C486591:PARVB protein, human; D050796:STAT3 Transcription Factor; D000185:Actinin