title: Cell-specific effects of miR-221/222 in vessels: molecular mechanism and therapeutic application.
abstract: MicroRNAs (miRNAs) are noncoding RNAs that impact almost every aspect of biology and disease. Until now, the cell-specific effects of miRNAs in cardiovascular system have not been established. In the current study, the cellular functions of miR-221 and miR-222 (miR-221/222) in vascular smooth muscle cells (VSMCs) and vascular endothelial cells (ECs) were compared. In cultured cells, we identified that the effects of miR-221/222 on proliferation, migration, and apoptosis are opposite between VSMCs and ECs. In VSMCs, miR-221/222 had effects of pro-proliferation, pro-migration, and anti-apoptosis. In contrast, miR-221/222 had effects of anti-proliferation, anti-migration, and pro-apoptosis in ECs. The different expression profiles of their target genes, p27(Kip1), p57(kip2), and c-kit between the two cell types might be related to the opposite effects. Finally, the opposite cellular effects of miR-221/222 were verified in vivo in balloon-injured rat carotid artery as demonstrated by different consequences in neointimal growth and re-endothelialization. The results suggest that the biological functions of miR-221/222 in vascular walls are cell-specific. The opposite cellular effects of miR-221/222 on VSMCs and ECs may have important therapeutic applications in many vascular diseases such as atherosclerosis and restenosis after angioplasty.
authors.affiliation: RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Cheng
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002339:Carotid Arteries / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D051381:Rats; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
chemical_list: D050761:Cyclin-Dependent Kinase Inhibitor p57; D035683:MicroRNAs; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019009:Proto-Oncogene Proteins c-kit