The prosurvival protein BAG3: a new participant in vascular homeostasis

Cell Death and Disease - Tập 7 Số 10 - Trang e2431-e2431
Albino Carrizzo1, Antonio Damato1, Mariateresa Ambrosio1, Antonia Falco2,3, Alessandra Rosati4,3, Mario Capunzo4, Michele Madonna1, Maria Caterina Turco4,3, James L. Januzzi5, Vincenzo De Laurenzi6,3, Carmine Vecchione4,1
1IRCCS Neuromed, Pozzilli (IS), Italy
2Department of Pharmacy, University of Salerno, Fisciano, SA, Italy
3Vascular Pathophysiology Unit, Biouniversa s.r.l., c/o University of Salerno, Fisciano (SA), Italy
4Department of Medicine and Surgery, University of Salerno, Baronissi, SA, Italy
5Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, USA
6Dipartimento di Scienze Mediche, Orali e Biotecnologiche, CeSI, Universita' 'G. D'Annunzio' di Chieti e Pescara, Pescara, Italy

Tóm tắt

AbstractBcl2-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.

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Cell Death and Disease

Tập 7 Số 10

e2431-e2431

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