The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia.

The proliferation and remodeling of vascular smooth muscle cells (VSMCs) is an important pathological event in atherosclerosis and restenosis. Here we report that microRNA-132 (miR-132) blocks vascular smooth muscle cells (VSMC) proliferation by inhibiting the expression of LRRFIP1 [leucine-rich repeat (in Flightless 1) interacting protein-1]. MicroRNA microarray revealed that miR-132 was upregulated in the rat carotid artery after catheter injury, which was further confirmed by quantitative real-time RT-PCR. Transfection of a miR-132 mimic significantly inhibited the proliferation of VSMCs, whereas transfection of a miR-132 antagomir increased it. miR-132 mimic inhibited VSMC migration and induced apoptosis. miR-132 mimic increased the protein amounts of both p27 and smooth muscle (SM) α-actin, whereas it decreased SM α-actin and Bcl2. Bioinformatics showed that LRRFIP1 is a target candidate of miR-132. miR-132 down-regulated luciferase activity driven by a vector containing the 3'-untranslated region of Lrrfip1 in a sequence-specific manner. LRRFIP1 induced VSMC proliferation and increased phosphorylation of ERK. Immunohistochemical analysis revealed that Lrrfip1 was clearly expressed along with the basal laminar area of smooth muscle, and its expression pattern was disrupted 7 days after arterial injury. LRRFIP1 mRNA was decreased 14 days after injury. Delivery of miR-132 to rat carotid artery reduced LRRFIP1 expression and attenuated neointimal proliferation in carotid artery injury models. Our results suggest that miR-132 is a novel regulator of VSMC proliferation that represses neointimal formation by inhibiting LRRFIP1 expression.

Choe N ，Kwon JS ，Kim JR ，Eom GH ，Kim Y ，Nam KI ，Ahn Y ，Kee HJ ，Kook H ... -  《-》

The microRNA miR-34c inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia by targeting stem cell factor.

The fine balance between proliferation and differentiation of vascular smooth muscle cells (VSMCs) is indispensable for the maintenance of healthy blood vessels, whereas an increase in proliferation participates in pathologic cardiovascular events such as atherosclerosis and restenosis. Here we report that microRNA-34c (miR-34c) targets stem cell factor (SCF) to inhibit VSMC proliferation and neointimal hyperplasia. In an animal model, miR-34c was significantly increased in the rat carotid artery after catheter injury. Transient transfection of miR-34c to either VSMCs or A10 cells inhibited cell survival by inducing apoptosis, which was accompanied by an increase in expression of p21, p27, and Bax. Transfection of miR-34c also attenuated VSMC migration. Bioinformatics showed that SCF is a target candidate of miR-34c. miR-34c down-regulated luciferase activity driven by a vector containing the 3'-untranslated region of SCF in a sequence-specific manner. Forced expression of SCF in A10 cells induced proliferation and migration, whereas knocking-down of SCF reduced cell survival and migration. miR-34c antagomir-induced VSMC proliferation was blocked by SCF siRNA. Delivery of miR-34c to rat carotid artery attenuated the expression of SCF and blocked neointimal hyperplasia. These results suggest that miR-34c is a new modulator of VSMC proliferation and that it inhibits neointima formation by regulating SCF.

Choe N ，Kwon JS ，Kim YS ，Eom GH ，Ahn YK ，Baik YH ，Park HY ，Kook H ... -  《-》

MicroRNA 181b promotes vascular smooth muscle cells proliferation through activation of PI3K and MAPK pathways.

Li TJ ，Chen YL ，Gua CJ ，Xue SJ ，Ma SM ，Li XD ... -  《International Journal of Clinical and Experimental Pathology》

MicroRNA-24 Attenuates Neointimal Hyperplasia in the Diabetic Rat Carotid Artery Injury Model by Inhibiting Wnt4 Signaling Pathway.

Yang J ，Fan Z ，Yang J ，Ding J ，Yang C ，Chen L ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Intercellular transfer of miR-126-3p by endothelial microparticles reduces vascular smooth muscle cell proliferation and limits neointima formation by inhibiting LRP6.

Vascular smooth muscle cell (VSMC) proliferation is of importance in the pathogenesis of vascular diseases such as restenosis or atherosclerosis. Endothelial microparticles (EMPs) regulate function and phenotype of target endothelial cells (ECs), but their influence on VSMC biology is unknown. We aim to investigate the role of EMPs in the regulation of vascular smooth muscle cell (VSMC) proliferation and vascular remodeling. Systemic treatment of mice with EMPs after vascular injury reduced neointima formation in vivo. In vitro, EMP uptake in VSMCs diminished VSMC proliferation and migration, both pivotal steps in neointima formation. To explore the underlying mechanisms, Taqman microRNA-array was performed and miR-126-3p was identified as the predominantly expressed miR in EMPs. Confocal microscopy revealed an EMP-mediated miR-126 transfer into recipient VSMCs. Expression of miR-126 target protein LRP6, regulating VSMC proliferation, was reduced in VSMCs after EMP treatment. Importantly, genetic regulation of miR-126 in EMPs showed a miR-126-dependent inhibition of LRP6 expression, VSMC proliferation and neointima formation in vitro and in vivo, suggesting a crucial role of miR-126 in EMP-mediated neointima formation reduction. Finally, analysis of miR-126 expression in circulating MPs in 176 patients with coronary artery disease revealed a reduced PCI rate in patients with high miR-126 expression level, supporting a central role for MP-incorporated miR-126 in vascular remodelling. EMPs reduce VSMC proliferation, migration and subsequent neointima formation by delivering functional miR-126 into recipient VSMCs.

Jansen F ，Stumpf T ，Proebsting S ，Franklin BS ，Wenzel D ，Pfeifer P ，Flender A ，Schmitz T ，Yang X ，Fleischmann BK ，Nickenig G ，Werner N ... -  《-》