Abstract 173: Proprotein Convertase Subtilisin/Kexin Type 6 is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Disease

Proprotein convertases (PCSKs) process matrix metalloproteases (MMPs) and cytokines. Apart from PCSK9, the role of these enzymes in vascular disease is largely unknown. Previously, we demonstrated upregulation of PCSK6 in carotid atherosclerosis, primarily localized to smooth muscle cells (SMCs) and positively correlated to inflammation, extracellular matrix remodeling and cytokines. Here, we extended these findings to determine the role of PCSK6 in vascular development and disease. Increased expression of PCSK6 in vascular disease was validated by microarrays from two non-overlapping cohorts of carotid plaques vs. non-atherosclerotic arteries (n=50 patients and n=32 patients, p0.7, p0.5, p-/- mice did not present an obvious vascular phenotype but showed reduced intimal hyperplasia compared to wild-type mice after carotid artery ligation (p=0.015). In vitro, PCSK6 overexpression markedly increased SMC migration upon PDGFBB stimulation (p