Abstract 512: Collagen Homologous Sequence R1R2 Mediates Vascular Remodeling by Decreasing Inflammation and Smooth Muscle Proliferation
The extracellular matrix (ECM) is a major constituent of the vessel wall. Except for providing a structural scaffold for cells, ECM controls numerous cellular functions like adhesion, growth, migration and differentiation. The components of ECM are mediated by the interplay between ECM synthesis, deposition, degradation and the interaction between ECM proteins. Vascular remodeling occurs in the vascular diseases and is characterized by endothelial cell activation, inflammatory cell infiltration, smooth muscle cell (SMC) proliferation/migration, and augmented deposition of ECM proteins. Collagen I is the major ECM component in the arterial wall, excess collagen I accumulation may exacerbate the vascular disease by further facilitating SMC proliferation/migration. Therefore, treatments to inhibit excess collagen deposition could provide a remedy for vascular disease. R1R2, a peptide derived from the bacterial adhesin SFS with sequence homology to collagen, is known to inhibit collagen I deposition by inhibiting the binding of fibronectin to collagen. Studies have revealed that R1R2 affects collagen I-dependent cell growth and migration in vitro. However, the in vivo functions of R1R2 during vascular remodeling remain unknown. We hypothesized that R1R2 prevents excess collagen I accumulation and SMC proliferation, resulting in decreased neointimal formation. We induced vascular remodeling by ligating the carotid artery on mice. Delivery of R1R2 was periadventially applied using pluronic gel and evaluated its effects on vascular remodeling, ECM deposition, SMC proliferation and differentiation. Morphometric analysis demonstrated that R1R2 reduced intima-media thickening by 50% compared to the control group. R1R2 treatment also decreased collagen I deposition in the vessel wall and maintained SMC in the contractile phenotype. Interestingly, R1R2 dramatically reduced inflammatory cell infiltration into the vessel by 80% accompanied with decreased VCAM-1 and ICAM-1. In conclusion, our data showed that R1R2 attenuates the vascular remodeling response by decreasing inflammation and SMC proliferation/migration. These studies provide a therapeutic potential of periadventitially delivering R1R2 in treating vascular diseases.
Author Disclosures: T. Lee: None. H. Chiang: None.
- © 2014 by American Heart Association, Inc.