MicroRNA-195 regulates vascular smooth muscle cell phenotype and prevents neointimal formation.
OBJECTIVE
Proliferation and migration of vascular smooth muscle cells (VSMCs) can cause atherosclerosis and neointimal formation. MicroRNAs have been shown to regulate cell proliferation and phenotype transformation. We discovered abundant expression of microRNA-195 in VSMCs and conducted a series of studies to identify its function in the cardiovascular system.


RESULTS
MicroRNA-195 expression was initially found to be altered when VSMCs were treated with oxidized low-density lipoprotein (oxLDL) in a non-replicated microRNA array experiment. Using cellular studies, we found that microRNA-195 reduced VSMC proliferation, migration, and synthesis of IL-1β, IL-6, and IL-8. Using bioinformatics prediction and experimental studies, we showed that microRNA-195 could repress the expression of Cdc42, CCND1, and FGF1 genes. Using a rat model, we found that the microRNA-195 gene, introduced by adenovirus, substantially reduced neointimal formation in a balloon-injured carotid artery. In situ hybridization confirmed the presence of microRNA-195 in the treated arteries but not in control arteries. Immunohistochemistry experiments showed abundant Cdc42 in the neointima of treated arteries.


CONCLUSIONS
We showed that microRNA-195 plays a role in the cardiovascular system by inhibiting VSMC proliferation, migration, and proinflammatory biomarkers. MicroRNA-195 may have the potential to reduce neointimal formation in patients receiving stenting or angioplasty.
Department of Genome Medicine,  Kaohsiung Medical University, No. 100, TzYou First Road, Kaohsiung 80708,  Taiwan.
Yung-Song
YS
Wang
Hay-Yan J
HY
Wang
Yi-Chu
YC
Liao
Pei-Chien
PC
Tsai
Ku-Chung
KC
Chen
Hsin-Yun
HY
Cheng
Ruey-Tay
RT
Lin
Suh-Hang Hank
SH
Juo
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D019295:Computational Biology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D058426:Neointima; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
C530104:CCND1 protein, human; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008077:Lipoproteins, LDL; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; C099252:oxidized low density lipoprotein; D016220:Fibroblast Growth Factor 1; D019938:Cyclin D1; D020764:cdc42 GTP-Binding Protein