An endocrine genetic signal between blood cells and vascular smooth muscle cells: Role of microRNA-223 in smooth muscle function and atherogenesis

Zhen Shan, Shanshan Qin, Wen Li, Weibin Wu, Jian Yang, Maoping Chu, Xiaokun Li, Yuqing Huo, Gary L. Schaer, Shenming Wang, Chunxiang Zhang

Research output: Contribution to journalArticle

56 Scopus citations

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. Objectives 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.

Original languageEnglish (US)
Pages (from-to)2526-2537
Number of pages12
JournalJournal of the American College of Cardiology
Volume65
Issue number23
DOIs
StatePublished - Jun 16 2015

Keywords

  • atherosclerosis
  • bone marrow
  • insulin-like growth factor 1 receptor
  • microRNAs

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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