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An Endocrine Genetic Signal Between Blood Cells and Vascular Smooth Muscle Cells: Role of MicroRNA-223 in Smooth Muscle Function and Atherogenesis.

Authors: Shan, Zhen  Qin, Shanshan  Li, Wen  Wu, Weibin  Yang, Jian  Chu, Maoping  Li, Xiaokun  Huo, Yuqing  Schaer, Gary L  Wang, Shenming  Zhang, Chunxiang 
Citation: Shan Z, etal., J Am Coll Cardiol. 2015 Jun 16;65(23):2526-37. doi: 10.1016/j.jacc.2015.03.570.
Pubmed: (View Article at PubMed) PMID:26065992
DOI: Full-text: DOI:10.1016/j.jacc.2015.03.570


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.

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CRRD Object Information
CRRD ID: 25824846
Created: 2020-05-04
Species: All species
Last Modified: 2020-05-04
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.