title: The prosurvival protein BAG3: a new participant in vascular homeostasis.
abstract: Bcl2-associated athanogene 3 (BAG3), is constitutively expressed in a few normal cell types, including myocytes, peripheral nerves and in the brain, and is also expressed in certain tumors. To date, the main studies about the role of BAG3 are focused on its pro-survival effect in tumors through various mechanisms that vary according to cellular type. Recently, elevated concentrations of a soluble form of BAG3 were described in patients affected by advanced stage of heart failure (HF), identifying BAG3 as a potentially useful biomarker in monitoring HF progression. Despite the finding of high levels of BAG3 in the sera of HF patients, there are no data on its possible role on the modulation of vascular tone and blood pressure levels. The aim of this study was to investigate the possible hemodynamic effects of BAG3 performing both in vitro and in vivo experiments. Through vascular reactivity studies, we demonstrate that BAG3 is capable of evoking dose-dependent vasorelaxation. Of note, BAG3 exerts its vasorelaxant effect on resistance vessels, typically involved in the blood pressure regulation. Our data further show that the molecular mechanism through which BAG3 exerts this effect is the activation of the PI3K/Akt signalling pathway leading to nitric oxide release by endothelial cells. Finally, we show that in vivo BAG3 administration is capable of regulating blood pressure and that this is dependent on eNOS regulation since this ability is lost in eNOS KO animals.
authors.affiliation: IRCCS Neuromed, Pozzilli (IS), Italy.
authors.forename: Albino
authors.initials: A
authors.lastname: Carrizzo
authors.affiliation: IRCCS Neuromed, Pozzilli (IS), Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Damato
authors.affiliation: IRCCS Neuromed, Pozzilli (IS), Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Ambrosio
authors.affiliation: Vascular Pathophysiology Unit, Biouniversa s.r.l., c/o University of Salerno, Fisciano (SA), Italy.|Department of Pharmacy, University of Salerno, Fisciano (SA), Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Falco
authors.affiliation: Vascular Pathophysiology Unit, Biouniversa s.r.l., c/o University of Salerno, Fisciano (SA), Italy.|Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rosati
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Capunzo
authors.affiliation: IRCCS Neuromed, Pozzilli (IS), Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Madonna
authors.affiliation: Vascular Pathophysiology Unit, Biouniversa s.r.l., c/o University of Salerno, Fisciano (SA), Italy.|Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Turco
authors.affiliation: Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: Vascular Pathophysiology Unit, Biouniversa s.r.l., c/o University of Salerno, Fisciano (SA), Italy.|Dipartimento di Scienze Mediche, Orali e Biotecnologiche, CeSI, Universita' 'G. D'Annunzio' di Chieti e Pescara, Pescara, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Laurenzi
authors.affiliation: IRCCS Neuromed, Pozzilli (IS), Italy.|Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Vecchione
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C498806:Bag3 protein, mouse; D010656:Phenylephrine; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt