Background　Extracellular　vesicles　(EVs)　from　vascular　adventitial　fibroblasts　(AFs)　contribute　to　the　proliferation　of　vascular　smooth　muscle　cells　(VSMCs)　and　vascular　remodeling　in　spontaneously　hypertensive　rat　(SHR).　This　study　shows　the　crucial　roles　of　EVs-mediated　miR135a-5p　transfer　in　VSMC　proliferation　and　the　underlying　mechanisms　in　hypertension.　Methods　AFs　and　VSMCs　were　obtained　from　the　aorta　of　Wistar-Kyoto　rat　(WKY)　and　SHR.　EVs　were　isolated　from　the　culture　of　AFs　with　ultracentrifugation　method.　Results　MiR135a-5p　level　in　SHR-EVs　was　significantly　increased.　MiR135a-5p　inhibitor　prevented　the　SHR-EVsinduced　VSMC　proliferation.　Fibronectin　type　III　domain　containing　5　(FNDC5)　was　a　target　gene　of　miR135a5p.　FNDC5　level　was　lower　in　VSMCs　of　SHR.　MiR135a-5p　inhibitor　not　only　increased　FNDC5　expression,　but　reversed　the　SHR-EVs-induced　FNDC5　downregulation　in　VSMCs　of　SHR.　MiR135a-5p　mimic　inhibited　FNDC5　expression,　but　failed　to　promote　the　SHR-EVs-induced　FNDC5　downregulation　in　VSMCs　of　SHR.　Exogenous　FNDC5　prevented　the　SHR-EVs-induced　VSMC　proliferation　of　both　WKY　and　SHR.　Knockdown　of　miR135a-5p　in　fibroblasts　completely　prevented　the　upregulation　of　miR135a-5p　in　the　EVs.　The　SHR-EVs　from　the　miR135a-5p　knockdown-treated　fibroblasts　lost　their　roles　in　inhibiting　FNDC5　expression　and　promoting　proliferation　in　VSMCs　of　both　WKY　and　SHR.　Conclusions　Increased　miR135a-5p　in　the　SHR-EVs　promoted　VSMC　proliferation　of　WKY　and　SHR　via　inhibiting　FNDC5　expression.　MiR135a-5p　and　FNDC5　are　crucial　targets　for　intervention　of　VSMC　proliferation　in　hypertension.