Heme oxygenase-1 inhibition prevents intimal hyperplasia enhancing nitric oxide-dependent apoptosis of vascular smooth muscle cells
Articolo
Data di Pubblicazione:
2011
Citazione:
Heme oxygenase-1 inhibition prevents intimal hyperplasia enhancing nitric oxide-dependent apoptosis of vascular smooth muscle cells / M.G. Cerrito, A. Scagliarini, A. Froio, A. Liloia, M. Busnelli, R. Giovannoni, L.E. Otterbein, L. Mainetti, M. Villa, F.H. Bach, B.E. Leone, G.M. Biasi, M. Lavitrano. - In: BIOLOGICAL & PHARMACEUTICAL BULLETIN. - ISSN 0918-6158. - 34:8(2011), pp. 1204-1214. [10.1248/bpb.34.1204]
Abstract:
Heme oxygenase-1 (HO-1, encoded by the HMOX1 gene) and inducible nitric oxide synthase (iNOS) have been implicated in vascular disease; however the role of these genes remains unclear. Therefore, we studied the mechanism by which iNOS-derived nitric oxide (NO) affects the intimal hyperplasia (IH) formation in relation to HO-1. We show, in a model of balloon injury in rats, that the suppression of vascular smooth muscle cells (VSMC) proliferation by NO required HO-1, while induction of apoptosis of the VSMC by NO does not involve HO-1. To better clarify the molecular mechanism of this finding, we used Hmox1+/+ and Hmox1-/- VSMC exposed to NO. In Hmox1+/+ VSMC, NO is antiproliferative (up to 34% inhibition) and it is associated to an increase of apoptosis (up to 35%) due to a decrease of X-linked inhibitor of apoptosis protein (XIAP) expression level and to the activation of caspase-3. In the absence of HO-1 (Hmox1-/- VSMC) apoptosis was significantly greater (69% p<0.01 vs. Hmox1+/+ VSMC) demonstrating that HO-1 attenuated the pro-apoptotic effect of NO on VSMC. In the context of IH, the pro-apoptotic effect of NO on VSMC is increased in the absence of HO-1 and exerts therapeutic effects with a significant reduction in IH.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Apoptosis; Heme oxygenase-1; Intimal hyperplasia; Nitric oxide; Proliferation; Animals; Caspase 3; Cell Proliferation; Disease Models, Animal; Gene Expression; Heme Oxygenase-1; Hyperplasia; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Tunica Intima; X-Linked Inhibitor of Apoptosis Protein; Apoptosis
Elenco autori:
M.G. Cerrito, A. Scagliarini, A. Froio, A. Liloia, M. Busnelli, R. Giovannoni, L.E. Otterbein, L. Mainetti, M. Villa, F.H. Bach, B.E. Leone, G.M. Biasi, M. Lavitrano
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