Abstract 13618: Effects of Type 1 Interferon on Blood-derived Smooth Muscle Progenitor Cells Differentiation and Arterial Wall
Introduction: System lupus erythematosus (SLE) patients have premature atherosclerosis not explained by traditional risk factors and half have elevated Type-I Interferon (IFN-I) levels.
Hypothesis: We hypothesized that IFN-I would induce premature atherosclerosis by affecting the differentiation of circulating smooth muscle progenitor cells (SMPC) and promoting atherosclerosis within the vasculature.
Methods: SMPC isolated from wild-type (WT) and IFN receptor knock-out (IFNR-KO) animals were cultured in medium ± IFN-I and ± TGF-β. In vivo, we analyzed the effect of muscle electroporation of IFN-I cDNA on the number of SMPC and sections of the abdominal aorta bifurcation.
Results: After 2 weeks culture, IFN-I containing media led to an increase in the number of SMPC isolated from WT animals but no change when the SMPC were isolated from IFNR-KO mice. When the cultured cells were sorted, there was little monocytes/macrophage (CD14, CD36 and F4/80) marker expression while the expression of CD34 increased 50% (Figure), approximately. Real-time PCR revealed that the mRNA of calponin, SM-α-actin and SM22 increased 0.33, 4.5 and 75.1 times, respectively, while SM-myosin heavy chain was unchanged after treatment with IFN-I. Our in vivo results demonstrate a marked increase in pre-atherosclerotic like lesions and significant endothelium damage in WT mice expressing IFN-I for 3 months. However, there was no significant difference in arterial media thickness and cell density between IFN-I treated mice and control. Within these lesions, we observed “immature SMC,” cells that expressed CD34, SM-α-actin, but no SM myosin heavy chain (Figure).
Conclusions: Our findings suggest that IFN-I enhances SMPC number, and maintains them in an “immature” state while TGF-β might skew SMPC along a non-SMC pathway. These results suggest a role of IFN-I in atherosclerosis by affecting SMPC maturation and have implications for the pathogenesis of atherosclerosis in lupus patients.
Author Disclosures: Y. Diao: None. R. Mohandas: None. P. Lee: None. Z. Liu: None. L. Sautina: None. W. Mu: None. L. Shiyu: None. X. Wen: None. B. Croker: None. M. Segal: None.
- © 2015 by American Heart Association, Inc.