MiR-320a contributes to atherogenesis by augmenting multiple risk factors and down-regulating SRF.
Atherosclerosis progress is regulated by a variety of factors. Here, we show that miR-320a, an intergenic miRNA, is markedly elevated in the peripheral blood of coronary heart disease patients and high-risk patients. Microarray analysis and qRT-PCR assays showed that circulating miRNA-320a was highly expressed in coronary artery disease patients. In vivo study showed that overexpression of miR-320a resulted in significant increase in levels of plasma lipid (total cholesterol, Triglyceride and low-density lipoprotein) and serum inflammatory cytokines (IL-6, MCP-1, sICAM, pSelectin, TNF-α and fibrinogen). In ApoE(-/-) mice, miR-320a expression attenuates endothelium cell function and promotes atherogenesis. Bioinformatics analysis identified serum response factor as a potential target for miR-320a, which was validated by luciferase reporter activity assay and western-blot in vitro and in vivo. Moreover, miR-320a expression inhibits human-derived endothelium cell proliferation and induces apoptosis. We also found that SP1 transcriptionally up-regulates hsa-miR-320a expression. Our observations indicate that miR-320a is a key regulator contributing to multiple aspects of atherogenesis.
Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chen
C
Chen
Yan
Y
Wang
Shenglan
S
Yang
Huaping
H
Li
Gang
G
Zhao
Feng
F
Wang
Lei
L
Yang
Dao Wen
DW
Wang
D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics*; D015153:Blotting, Western; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D026362:Serum Response Factor / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D001057:Apolipoproteins E; D016207:Cytokines; D008055:Lipids; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; C541056:Mirn320 microRNA, mouse; D026362:Serum Response Factor; D016329:Sp1 Transcription Factor
SRF; atherosclerosis; endothelium; miRNA