TY - JOUR
T1 - An endocrine genetic signal between blood cells and vascular smooth muscle cells
T2 - Role of microRNA-223 in smooth muscle function and atherogenesis
AU - Shan, Zhen
AU - Qin, Shanshan
AU - Li, Wen
AU - Wu, Weibin
AU - Yang, Jian
AU - Chu, Maoping
AU - Li, Xiaokun
AU - Huo, Yuqing
AU - Schaer, Gary L.
AU - Wang, Shenming
AU - Zhang, Chunxiang
N1 - Publisher Copyright:
© 2015 American College of Cardiology Foundation.
PY - 2015/6/16
Y1 - 2015/6/16
N2 - 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.
AB - 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.
KW - atherosclerosis
KW - bone marrow
KW - insulin-like growth factor 1 receptor
KW - microRNAs
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U2 - 10.1016/j.jacc.2015.03.570
DO - 10.1016/j.jacc.2015.03.570
M3 - Article
C2 - 26065992
AN - SCOPUS:84930733661
SN - 0735-1097
VL - 65
SP - 2526
EP - 2537
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 23
ER -