title: Effects of Long-Term Type I Interferon on the Arterial Wall and Smooth Muscle Progenitor Cells Differentiation.
abstract: OBJECTIVE
  Patients with systemic lupus erythematosis are at risk for premature atherosclerosis and half of the patients with systemic lupus erythematosis have elevated type I interferon (IFN-I) levels. We hypothesized that IFN-I would induce premature atherosclerosis by increasing the number of smooth muscle progenitor cells (SMPC) in the bloodstream and promoting atherosclerotic lesions within the vasculature.
  
  
  RESULTS
  SMPC isolated from wild-type and IFN receptor knockout animals were cultured in medium±IFN-I. In vivo, we used electroporation to generate stable IFN-I expression for as long as 4 months. The number of SMPC was determined in mice that expressed IFN-I and in control mice and sections from the bifurcation of the abdominal aorta were analyzed 3 months after electroporation of an IFN-I expression plasmid or a control plasmid. Adding IFN-I to the media increased the number of cultured wild-type SMPC and increased mRNA for SM22, but had no effect on SMPC isolated from IFN receptor knockout mice. Our in vivo results demonstrated a positive relationship between the preatherosclerotic-like lesions and endothelial damage. Although, there were no significant differences in smooth muscle cell density or thickness of the medial layer between groups, the IFN-I-expressing mice had a significant increase in preatherosclerotic-like lesions and immature smooth muscle cells, cells that expressed CD34 and smooth muscle α-actin; but lacked smooth muscle myosin heavy chain.
  
  
  CONCLUSIONS
  IFN-I seems to enhance SMPC number in vitro. In vivo IFN-I expression may maintain SMPC in an immature state. These immature smooth muscle cells could give rise to macrophages and eventually foam cells.
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.).
authors.forename: Yanpeng
authors.initials: Y
authors.lastname: Diao
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.).
authors.forename: Rajesh
authors.initials: R
authors.lastname: Mohandas
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.).
authors.forename: Pui
authors.initials: P
authors.lastname: Lee
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.).
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.).
authors.forename: Larysa
authors.initials: L
authors.lastname: Sautina
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.).
authors.forename: Wei
authors.initials: W
authors.lastname: Mu
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.).
authors.forename: Shiyu
authors.initials: S
authors.lastname: Li
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.).
authors.forename: Xuerong
authors.initials: X
authors.lastname: Wen
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.).
authors.forename: Byron
authors.initials: B
authors.lastname: Croker
authors.affiliation: From the Division of Nephrology, Hypertension, and Renal Transplantation (Y.D., R.M., P.L., L.S., W.M., S.L., X.W., M.S.S.) and Department of Pathology (B.C.), University of Florida, Gainesville; North Florida/South Georgia Veterans Health System, Gainesville (R.M., B.C., M.S.S.); and Division of Urology, Department of Surgery, The 2nd Teaching Hospital of Dalian Medical University, Dalian, China (Z.L.). segalms@medicine.ufl.edu.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Segal
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D007370:Interferon Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection
chemical_list: D018952:Antigens, CD34; D007370:Interferon Type I; D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin; D018995:Myosin Heavy Chains
keywords: actin; atherosclerosis; foam cells; interferons; macrophages