title: An Endocrine Genetic Signal Between Blood Cells and Vascular Smooth Muscle Cells: Role of MicroRNA-223 in Smooth Muscle Function and Atherogenesis.
abstract: BACKGROUND
  MicroRNA-223 (miR-223) is a hematopoietic lineage cell-specific microRNA. However, a significant amount of miR-223 has been identified in vascular smooth muscle cells (VSMCs) and vascular walls that should not have endogenous miR-223.
  
  
  OBJECTIVE
  This study sought to determine the sources of miR-223 in normal and atherosclerotic arteries and the role of miR-223 in atherogenesis.
  
  
  METHODS
  The levels and sources of miR-223 in blood cells (leukocytes and platelets), serum, blood microparticles, VSMCs, and vascular walls were determined. Both in vivo and in vitro studies were conducted to evaluate miR-223 secretion by blood cells and the ability of miR-223 to enter VSMCs and vascular walls. Subsequent changes in and the effects of miR-223 levels on serum and arteries in atherosclerotic animals and patients were investigated.
  
  
  RESULTS
  Blood cells were able to secrete miR-223 into serum. MicroRNA-223 from blood cells was the most abundant cell-free miRNA in blood. Blood cell-secreted miR-223 could enter VSMCs and vascular walls, which produced strong biological effects via its target genes. In both atherosclerotic apolipoprotein-E knockout mice and patients with atherosclerosis, miR-223 levels were significantly increased in serum and atherosclerotic vascular walls. The atherosclerotic lesions in apolipoprotein-E knockout mice were exacerbated by miR-223 knockdown. The effect of miR-223 on atherogenesis was verified using miR-223 knockout mice.
  
  
  CONCLUSIONS
  Blood cell-secreted miR-223 enters vascular cells and walls, and appears to play important roles in VSMC function and atherogenesis. As a novel endocrine genetic signal between blood cells and vascular cells, miR-223 may provide a novel mechanism and new therapeutic target for atherosclerosis.
authors.affiliation: Rush University Cardiovascular Research Center and Department of Pharmacology, Rush University Medical Center, Chicago, Illinois.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Rush University Cardiovascular Research Center and Department of Pharmacology, Rush University Medical Center, Chicago, Illinois.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Qin
authors.affiliation: Division of Vascular Surgery and the Laboratory of General Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Division of Vascular Surgery and the Laboratory of General Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Wu
authors.affiliation: Rush University Cardiovascular Research Center and Department of Pharmacology, Rush University Medical Center, Chicago, Illinois.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Wenzhou Medical University, Second Affiliated Hospital, Wenzhou, China.
authors.forename: Maoping
authors.initials: M
authors.lastname: Chu
authors.affiliation: Wenzhou Medical University, Second Affiliated Hospital, Wenzhou, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Health Sciences University, Augusta, Georgia.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Rush University Cardiovascular Research Center and Department of Pharmacology, Rush University Medical Center, Chicago, Illinois.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Schaer
authors.affiliation: Division of Vascular Surgery and the Laboratory of General Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: shenmingwang@hotmail.com.
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
authors.affiliation: Rush University Cardiovascular Research Center and Department of Pharmacology, Rush University Medical Center, Chicago, Illinois. Electronic address: chunxiang_zhang@rush.edu.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism*; D001773:Blood Cells / Q000502:physiology*; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C544877:MIRN223 microRNA, mouse; D035683:MicroRNAs
keywords: atherosclerosis; bone marrow; insulin-like growth factor 1 receptor; microRNAs