The molecular biology of furin-like proprotein convertases in vascular remodelling.

Vascular smooth muscle cell (VSMC) proliferation and migration represent key features in atherosclerosis and restenosis. The proprotein convertases (PCs) furin and PC5 are highly expressed in human atheroma and are putatively involved in vascular lesion formation via the activation of precursor proteins, essential for cell proliferation and migration. In vitro assays have identified these PCs to govern cell functions via endoproteolytic cleavage of key substrates, including pro-integrins and pro-matrix metalloproteinases. In vivo gene expression studies of furin/PC5 and their substrates demonstrate their coordinated regulation in animal models of vascular remodelling and in human atherosclerotic lesions. Here we describe in vitro and in vivo models to investigate the function of furin/PC5 in VSMCs and in vascular lesion formation. In conjunction with the development of novel PC inhibitors, this should facilitate the development of new strategies targeting PCs in cardiovascular disease.