S100A12 Links to Thoracic Aortic Aneurysms

Abstract

See related article, pages 145–154 Inflammatory processes are involved in many vascular diseases and have been linked to a diverse array of mediators. This includes advanced glycation end products (AGEs) that are a collection of chemical entities implicated in inflammation-associated vascular disorders, particularly atherosclerosis. A specific receptor (receptor for advanced glycation end products [RAGE]) has been implicated in mediating the effects of AGEs in promoting inflammation through activation of the nuclear factor κB system. Subsequently, it was recognized that RAGE may promote inflammation through activation by non glycated products. This includes a member of the S100/calgranulin family termed S100A12, calgranulin C, or extracellular newly identified RAGE-binding proteins (EN-RAGE). S100A12 is predominantly secreted from neutrophils that can activate RAGE on endothelial cells, macrophages, and lymphocytes.1 In this issue of Circulation Research , Hofmann Bowman et al2 provide evidence for a new pathological role of S100A12 in the development of thoracic aortic aneurysms (TAAs). The most common complication of TAAs is dilation and rupture of the ascending aorta. TAAs are frequently associated with a number of well-defined genetic determinants, although there remains many questions regarding the mechanistic basis for the development and propagation of aneurysms in this region.3,4 This study used a combination of mouse models and human tissue. Because S100A12 is not normally expressed in mice, transgenic mice were created to express the human protein under the control of the smooth muscle cell (SMC)-specific promoter SM22α. Convincing evidence was presented demonstrating expression of S100A12 in the aortic media of transgenic mice and in SMCs cultured from aortas of these mice. The accumulation of S100A12 protein in mouse aortas and cultured aortic SMCs was equivalent to extracts of human TAAs and SMCs cultured from human TAAs. This provides some assurance that the effects of S100A12 described in the …