Cited 21 times since 2005 (1.1 per year) source: EuropePMC Cardiovascular research, Volume 68, Issue 1, 1 1 2005, Pages 136-143 Involvement of furin-like proprotein convertases in the arterial response to injury. Sluijter JP, Verloop RE, Pulskens WP, Velema E, Grimbergen JM, Quax PH, Goumans MJ, Pasterkamp G, de Kleijn DP
Background
Furin-like proprotein convertases (PCs) are proteolytic activators of proproteins, like membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor beta (TGF-beta), that are described in the arterial response to injury. However, the involvement of furin-like PCs in the arterial response to injury has not been studied yet. We studied furin, MT1-MMP, MMP levels and TGF-beta signaling after arterial injury. We also investigated the effect of an inhibitor of furin-like PCs, alpha1-antitrypsin Portland (alpha1-PDX), on arterial injury following balloon dilation.
Methods and results
NZW rabbit femoral and iliac arteries (N=42) were balloon dilated unilaterally and harvested after 2, 7, 14, 28 or 42 days. Furin mRNA levels were increased after 2 and 7 days. MMP-2 and MT1-MMP levels were increased after day 7 and TGF-beta signaling, by phosphorylating Smad 1/5 and 2/3, was increased at all time points. Inhibition of furin-like PCs, by adenoviral over-expression of alpha1-PDX, blocked proTGF-beta activation and Smad phosphorylation, and reduced MT1-MMP and MMP-2 activation (N=5). In vivo adventitial inhibition of furin-like PCs (N=9) resulted in a reduction of 13.1+/-5.2% in advential and 23.6+/-7.9% in intimal areas (P<0.05), but had no effect on lumen size due to decreased vessel areas.
Conclusions
This study demonstrates that furin-like PCs are involved in the arterial response to injury possibly through activation of the TGF-beta-Smad signaling pathway and identifies furin-like PCs as a possible target to inhibit intimal hyperplasia.
