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Although we reported an associated increase in perivascular inflammation, the exact role of inflammatory cells in the development of pulmonary vascular remodeling remains unknown. In this study, HIV\u2013infected and cocaine (H+C)\u2013treated human monocyte derived macrophages released a higher number of extracellular vesicles (EVs), compared to HIV\u2010infected or uninfected cocaine\u2010treated macrophages, with a significant increase in the particle size range to 100\u2013150 nm. Treatment of primary human pulmonary arterial smooth muscle cells (HPASMCs) with these EVs resulted in a significant increase in smooth muscle proliferation. We also observed a significant increase in the miRNA\u2010130a level in the EVs derived from H+C\u2010treated macrophages that corresponded with the decrease in the expression of phosphatase and tensin homolog and tuberous sclerosis 1 and 2 and activation of PI3K\/protein kinase B signaling in HPASMCs on addition of these EVs. Transfection of HPASMCs with antagomir\u2010130a\u2013ameliorated the EV\u2010induced effect. Thus, we conclude that EVs derived from H+C\u2010treated macrophages promote pulmonary smooth muscle proliferation by delivery of its prosurvival miRNA cargo, which may play a crucial role in the development of PAH.\u2014Sharma, H., Chinnappan, M., Agarwal, S., Dalvi, P., Gunewardena, S., O'Brien\u2010Ladner, A., Dhillon, N. K. Macrophage\u2010derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse. FASEBJ. 32, 5174\u20135185 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701558r","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T16:10:56Z","timestamp":1524154256000},"page":"5174-5185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Macrophage\u2010derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse"],"prefix":"10.1096","volume":"32","author":[{"given":"Himanshu","family":"Sharma","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahendran","family":"Chinnappan","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuti","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranjali","family":"Dalvi","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumedha","family":"Gunewardena","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Kansas Medical Center Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"O'Brien-Ladner","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Navneet K.","family":"Dhillon","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Kansas City Kansas USA"},{"name":"Department of Molecular and Integrative Physiology University of Kansas Medical Center Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200704-541OC"},{"key":"e_1_2_7_3_1","first-page":"25","article-title":"Pulmonary arterial hypertension among HIV-infected children: results of a national survey and review of the literature","volume":"3","author":"L'Huillier A. 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