Meta-iodobenzylguanidine, an inhibitor of arginine-dependent mono(ADP-ribosyl)ation, prevents neointimal hyperplasia.

The association of ADP-ribosylation with cell proliferation and ischemia-reperfusion injury suggests that it may be a suitable target for therapeutic control of revascularization-induced injury. The purpose of this study was to investigate the inhibitory actions of ADP-ribosylation inhibitors on restenosis. In organ culture, the poly(ADP-ribose) polymerase (PARP) inhibitor 3,4-dihydro-5-methylisoquinolinone (PD128763) was unable to prevent neointimal hyperplasia, whereas the arginine-dependent mono(ADP-ribosyl)transferase (ART) inhibitor meta-iodobenzylguanidine (MIBG) was highly effective (EC(50) 21 microM).

NF-kappaB activation is essential for angiotensin II-dependent proliferation and migration of vascular smooth muscle cells.

Angiotensin II (AngII) functions as a stress hormone under conditions of stretch, pressure and injury to stimulate smooth muscle cell migration and proliferation. Since the cellular response to stress is mediated in part by the transcription factor NF-kappaB, the relationship between AngII and NF-kappaB was investigated. Our study revealed that AngII promoted a dose-dependent and transient phosphorylation of the regulatory IkappaBalpha protein in smooth muscle cells from porcine coronary artery, with concomitant nuclear translocation of NF-kappaB and increased binding to a kappaB promoter element.