Abstract 9982: Long-term Administration of Type-I Interferon Leads to Premature Atherosclerosis

• Published in: Circulation (New York, N.Y.) N.Y.), 2013-11, Vol.128 (suppl_22)
• Main Authors: Diao, Yanpeng, Lee, Pui, Sautina, Larysa, Mohandas, Rajesh, Segal, Mark
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.128.suppl_22.A9982

Abstract only Introduction: Disease states such as SLE, CMV, and HIV are associated with elevated type I interferon (IFN-I) and increased cardiovascular risk. Previously we have demonstrated that IFN-I has detrimental effects on endothelial progenitor cells that could contribute to the atherosclerosis. However, the relationship between IFN-I and smooth muscle progenitor cells (SMPC), cells derived from the bone marrow that can differentiate into mature SMC, has not been determined. We hypothesized that IFN-I could induce premature atherosclerosis by increasing the number of SMPC in the bloodstream and increasing the number of immature SMC within the vasculature. Methods: In vitro, SMPC isolated from wild-type (WT) and IFN receptor knock-out (IFNR-KO) animals, were cultured in medium plus or minus IFN-1. In vivo, two mice models of long-term IFN-I exposure (electroporation of an IFN-I plasmid, or Q 3 day IFN-I i.p. injection for 3 months) were studied and the number of SMPC and degree of atherosclerosis were analyzed. Results: The number of SMPC from WT animals was significantly increased when cultured in medium plus IFN-I. However, IFN-I had no effect in the SMPC from IFNR-KO mice. Increased SMPC numbers were also observed in mice treated with or that expressed IFN-I. In addition, atherosclerotic-like lesions were found in the arterial wall in WT mice expressing IFN-I. Within the lesions we observed CD34+/smooth muscle α-actin+ expressing cells (Fig). These cells did not express smooth muscle myosin heavy chain, suggesting that they were immature SMC. Conclusions: For the first time we demonstrated that elevated IFN-I levels, found in a number of disease states, could lead to an atherosclerosis-like lesion. In concert with our previous work, this work suggests a complex interplay between the bone marrow, circulating cells, and the vessel wall leading to IFN-I mediated atherosclerosis. This has profound implications for cardiovascular disease in a number of disease states.