Abstract 20139: Loss of Sam68 Attenuates Inflammatory Response in Injured Arteries and Enhances Recovery

Background: The role of Src-associated in mitosis 68 kDa (Sam68) protein in cardiovascular biology is unknown. We sought to determine whether Sam68 regulates vascular remodeling after injury. Methods & Results: After carotid artery endothelial denudation injury, Sam68-/- mice displayed an accelerated re-endothelialization (P<0.05 at day 5 post-injury) and attenuated neointima formation (P<0.05, at day 14), which was associated with reduced macrophage infiltration and lowered expression of pro-inflammatory cytokines (i.e., TNF-a, IL-1b, IL-6 and MCP-1) in the injured vessels. The improved carotid recovery in Sam68-/- mice was recapitulated in WT mice that had received Sam68-/- bone-marrow (BM) transplantation, and in our newly-generated CreLysM;Sam68fl/fl mice, suggesting that Sam68 impedes vascular recovery primarily by its function in macrophages. In cultured Raw264.7 macrophages, knockdown of Sam68 resulted in a significant reduction in the TNF-a-induced expression of pro-inflammatory cytokines and in t...