PMID- 31871958 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231225 IS - 2329-0501 (Print) IS - 2329-0501 (Electronic) IS - 2329-0501 (Linking) VI - 16 DP - 2020 Mar 13 TI - Adipose Mesenchymal Cells-Derived EVs Alleviate DOCA-Salt-Induced Hypertension by Promoting Cardio-Renal Protection. PG - 63-77 LID - 10.1016/j.omtm.2019.11.002 [doi] AB - Hypertension is a long-term condition that can increase organ susceptibility to insults and lead to severe complications such as chronic kidney disease (CKD). Extracellular vesicles (EVs) are cell-derived membrane structures that participate in cell-cell communication by exporting encapsulated molecules to target cells, regulating physiological and pathological processes. We here demonstrate that multiple administration of EVs from adipose-derived mesenchymal stromal cells (ASC-EVs) in deoxycorticosterone acetate (DOCA)-salt hypertensive model can protect renal tissue by maintaining its filtration capacity. Indeed, ASC-EVs downregulated the pro-inflammatory molecules monocyte chemoattracting protein-1 (MCP-1) and plasminogen activating inhibitor-1 (PAI1) and reduced recruitment of macrophages in the kidney. Moreover, ASC-EVs prevented cardiac tissue fibrosis and maintained blood pressure within normal levels, thus demonstrating their multiple favorable effects in different organs. By applying microRNA (miRNA) microarray profile of the kidney of DOCA-salt rats, we identified a selective miRNA signature associated with epithelial-mesenchymal transition (EMT). One of the key pathways found was the axis miR-200-TGF-beta, that was significantly altered by EV administration, thereby affecting the EMT signaling and preventing renal inflammatory response and fibrosis development. Our results indicate that EVs can be a potent therapeutic tool for the treatment of hypertension-induced CKD in cardio-renal syndrome. CI - (c) 2019 The Authors. FAU - Lindoso, Rafael Soares AU - Lindoso RS AD - Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. AD - National Center for Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. AD - National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. FAU - Lopes, Jarlene Alecia AU - Lopes JA AD - Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. AD - National Center for Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. FAU - Binato, Renata AU - Binato R AD - Brazilian National Institute of Cancer, 20230-130 Rio de Janeiro, Brazil. FAU - Abdelhay, Eliana AU - Abdelhay E AD - Brazilian National Institute of Cancer, 20230-130 Rio de Janeiro, Brazil. FAU - Takiya, Christina Maeda AU - Takiya CM AD - Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. FAU - Miranda, Kildare Rocha de AU - Miranda KR AD - Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. AD - National Center for Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. FAU - Lara, Lucienne Silva AU - Lara LS AD - Institute of Biomedical Sciences, Federal University of Rio de Janeiro, 21941-590 Rio de Janeiro, Brazil. FAU - Viola, Antonella AU - Viola A AD - Department of Biomedical Sciences and Pediatric Research Institute "Citta della Speranza," University of Padova, 35131 Padua, Italy. FAU - Bussolati, Benedetta AU - Bussolati B AD - Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy. FAU - Vieyra, Adalberto AU - Vieyra A AD - Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. AD - National Center for Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. AD - National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. AD - Graduate Program of Translational Biomedicine/BIOTRANS, Grande Rio University, 25071-202 Duque de Caxias, Brazil. FAU - Collino, Federica AU - Collino F AD - Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. AD - National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. AD - Department of Biomedical Sciences and Pediatric Research Institute "Citta della Speranza," University of Padova, 35131 Padua, Italy. LA - eng PT - Journal Article DEP - 20191115 PL - United States TA - Mol Ther Methods Clin Dev JT - Molecular therapy. Methods & clinical development JID - 101624857 PMC - PMC6909095 OTO - NOTNLM OT - cardio-renal syndrome OT - chronic kidney disease OT - epithelial-mesenchymal transition OT - extracellular vesicles OT - hypertension OT - microRNAs EDAT- 2019/12/25 06:00 MHDA- 2019/12/25 06:01 PMCR- 2019/11/15 CRDT- 2019/12/25 06:00 PHST- 2019/09/10 00:00 [received] PHST- 2019/11/02 00:00 [accepted] PHST- 2019/12/25 06:00 [entrez] PHST- 2019/12/25 06:00 [pubmed] PHST- 2019/12/25 06:01 [medline] PHST- 2019/11/15 00:00 [pmc-release] AID - S2329-0501(19)30127-5 [pii] AID - 10.1016/j.omtm.2019.11.002 [doi] PST - epublish SO - Mol Ther Methods Clin Dev. 2019 Nov 15;16:63-77. doi: 10.1016/j.omtm.2019.11.002. eCollection 2020 Mar 13.