Identification and characterization of intimal smooth muscle cell with innate immune capacity in atherosclerosis

Abstract

Smooth muscle cells (SMC) contribute to the development and stability of atherosclerotic lesions. The phenotype transition and modulation of SMC is involved in many atherosclerotic pathological process. To date, more and more evidences indicated that innate immune response play important roles in atherosclerosis. As the first line of host defense and innate immunity, pathogen recognition receptors (PPR) have been shown to be involved in many mechanistic pathways in atherosclerosis. To investigate the role of innate immunity in SMC phenotype modulation in atherosclerosis, we analyzed PPR expression profile between different phenotypes of SMC and immune cells. Our data at the first time identified the high level of PPR expression in intimal SMC and characterized the comprehensive innate immune signatures. With comparison to other phenotypes of SMC and immune cells, we found intimal SMC possess a pro-inflammatory macrophage-like phenotype. To investigate the functional features and regulatory mechanism underlying the distinct phenotype, we used specific ligands for PRRs activation and showed that the innate immune capacity acquired by intimal SMC contribute to chemokine and cytokine secretion, migration promotion and extracellular matrix remodelling. Last but not least, we found the macrophage-like phenotype in intimal SMC and the pro-inflammatory capacity is associated with the elevated level of key transcription factors STAT1a, IRF8, IRF9, KLF4 and HIF2a. In conclusion, we propose a critical role of intimal SMC with innate immune capacity in the development of atherosclerosis. Targeting the phenotypic modulation of intimal SMC might be a new strategy for further clinical treatment.