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However, the mechanisms underlying these effects are incompletely understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Western blotting was used to compare the expression of key genes involved in vascular smooth muscle cell (VSMC) phenotype conversion. Recombinant adeno\u2010associated virus system was used to regulate miRNA expression in rats via tail vein. Bioinformatics was used to predict the transcriptional regulation of miR\u201021 upstream followed by biochemical validation using quantitative real\u2010time polymerase chain reaction, ChIP\u2010qPCR and EMSA assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Only the calcium antagonist amlodipine, and no other type of anti\u2010hypertensive drug, induced miR\u201021 overexpression in plasma and aortic vessels in the animal model. Real\u2010time PCR and luciferase assays showed that amlodipine induced miR\u201021 overexpression in vascular smooth muscle cells. Western blot and immunofluorescence assays demonstrated that amlodipine activated Akt2, rather than Akt1, followed by activation of transcription factor Sp1, which regulated VSMC phenotype conversion via binding to the miR\u201021 promoter. Furthermore, bioinformatic analyses and luciferase assays demonstrated that amlodipine activated miR\u201021 transcription at the \u20102034\/\u20102027 Sp1\u2010binding site, which was further demonstrated by ChIP\u2010qPCR and EMSA assays. Consistently, small\u2010interfering RNA\u2010mediated knockdown of Akt2 and Sp1 significantly attenuated the effects of amlodipine on miR\u201021 expression in smooth muscle cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>These results indicate that amlodipine induces smooth muscle cell differentiation via miR\u201021, which is regulated by p\u2010Akt2 and Sp1 nuclear translocation, thereby providing a novel target for cardiovascular diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14679","type":"journal-article","created":{"date-parts":[[2019,3,30]],"date-time":"2019-03-30T10:13:37Z","timestamp":1553940817000},"page":"2306-2320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Amlodipine induces vasodilation via Akt2\/Sp1\u2010activated miR\u201021 in smooth muscle 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