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SHR Neuro Cancer Cardio Lipid Metab Microb

Cerrito, MG; Scagliarini, A; Froio, A; Liloia, A; Busnelli, M; Giovannoni, R; Otterbein, LE; Mainetti, L; Villa, M; Bach, FH; Leone, BE; Biasi, GM; Lavitrano, M.
Heme Oxygenase-1 Inhibition Prevents Intimal Hyperplasia Enhancing Nitric Oxide-Dependent Apoptosis of Vascular Smooth Muscle Cells
BIOL PHARM BULL. 2011; 34(8): 1204-1214. Doi: 10.1248/bpb.34.1204
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Co-authors Med Uni Graz: Villa Matteo
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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.
Find related publications in this database (Keywords): nitric oxide; heme oxygenase-1; proliferation; apoptosis; intimal hyperplasia