system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Animals, Carotid Artery Diseases, Cell Adhesion, Cell Movement, Cells, Cultured, Integrin alphaV, Integrins, Muscle, Smooth, Vascular, Proprotein Convertase 5, Rats, Signal Transduction, Vitronectin.
user
Is endoproteolytic activation of alpha ( v ) integrin by proprotein convertase PC5 required for vascular smooth muscle cell adhesion to vitronectin and integrin-dependent signaling? Context: Integrins play an important role for vascular smooth muscle cell (VSMC) migration during the development of atherosclerosis and restenosis. Integrin alpha(v)-subunit consists of disulphide-bound 125-kDa heavy and 25-kDa light chains, which are generated by endoproteolytic cleavage. This type of activation requires the presence of suitable proprotein convertases (PCs). Based on ex vivo and in vitro data, the PC5 isozyme has been suggested to be the major integrin convertase. We have recently demonstrated that PC5 is upregulated during vascular remodeling in rodents, colocalizing with alpha(v) in VSMCs. The aim of this study was to investigate the activation of alpha(v) by PCs in VSMCs and its consequences for alpha(v)-dependent cell functions. Immunoblotting demonstrated that inhibition of PC activity by the specific pharmacological inhibitor dec-CMK inhibits alpha(v) cleavage in VSMCs. These results were confirmed using PC5-specific antisense oligonucleotides. PC5-antisense oligonucleotides and dec-CMK inhibited VSMC adhesion to the alpha(v)beta3/beta5 ligand vitronectin (both P<0.05). Furthermore, PC5-asODNs inhibited VSMC migration on vitronectin-coated wells (P<0.05). Inhibition of PC activity and consequently alpha(v) cleavage inhibited the adhesion-dependent focal adhesion kinase(Y397)-autophosphorylation and subsequent Akt activation, whereas phosphorylation of extracellular signal-regulated kinase 1/2 was not affected. In human endarterectomy lesions, PC5 colocalized with alpha(v) integrin in VSMCs in the atherosclerotic plaques.
assistant
The present study demonstrates that alpha(v) endoproteolytic activation is necessary for integrin-mediated adhesion and migration as well as signaling and requires PC5 in VSMCs. The colocalization of PC5 and alpha(v) in human carotid plaques indicates that PC5 might play a key role for alpha(v) activation in vivo. Final Decision: yes