Abstract 357: Intimal Smooth Muscle Cells Are Vascular Tissue Specific Innate Immune Effector Cell

Abstract

Intimal smooth muscle cells (SMC) represent the largest cell population in atherosclerotic plaques and restenotic lesions. These cells have multiple functions that differ from those of SMC of tunica media. Compared with medial SMC, intimal SMC are hyperresponsive to a large array of endogenous and exogenous inflammatory stimuli. However, the underlying molecular basis is elusive. Analyzing the phenotype of smooth muscle cells (SMC) isolated from balloon injury induced neointima of rat carotid artery, we found that unlike SMC of tunica media, the SMC of the intima exhibit an innate immune phenotype, characterized by constitutively expressing a broad panel of pathogen pattern recognition receptors (PRR) seen typically in macrophages. These PRR confer on intimal SMC an ability to react to an extensive list of microbial components by producing inflammatory mediators including nitric oxide, cytokines and chemokines. Additionally, intimal SMC produce the leukocyte chemokine CCL-5 (or RANTES) in the absence of exogenous stimuli, implying an intrinsic innate immune activity. The master program that determines the phenotype of intimal SMC remains to be defined but may involve a number of transcription pathways. These observations suggest that intimal SMC are vascular tissue specific innate immune effector cells with functions similar to those of macrophages.