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Distinct plasma gradients of microRNA-204 in the pulmonary circulation of patients suffering from WHO Groups I and II pulmonary hypertension
Pulmonary hypertension (PH), a heterogeneous vascular disease, consists of subtypes with overlapping clinical phenotypes. MicroRNAs, small non-coding RNAs that negatively regulate gene expression, have emerged as regulators of PH pathogenesis. The muscle-specific micro RNA (miR)-204 is known to be d...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440051/ https://www.ncbi.nlm.nih.gov/pubmed/30854934 http://dx.doi.org/10.1177/2045894019840646 |
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author | Estephan, Leonard E. Genuardi, Michael V. Kosanovich, Chad M. Risbano, Michael G. Zhang, Yingze Petro, Nancy Watson, Annie Al Aaraj, Yassmin Sembrat, John C. Rojas, Mauricio Goncharov, Dmitry A. Simon, Marc A. Goncharova, Elena A. Vaidya, Anjali Smith, Akaya Mazurek, Jeremy Han, Yuchi Chan, Stephen Y. |
author_facet | Estephan, Leonard E. Genuardi, Michael V. Kosanovich, Chad M. Risbano, Michael G. Zhang, Yingze Petro, Nancy Watson, Annie Al Aaraj, Yassmin Sembrat, John C. Rojas, Mauricio Goncharov, Dmitry A. Simon, Marc A. Goncharova, Elena A. Vaidya, Anjali Smith, Akaya Mazurek, Jeremy Han, Yuchi Chan, Stephen Y. |
author_sort | Estephan, Leonard E. |
collection | PubMed |
description | Pulmonary hypertension (PH), a heterogeneous vascular disease, consists of subtypes with overlapping clinical phenotypes. MicroRNAs, small non-coding RNAs that negatively regulate gene expression, have emerged as regulators of PH pathogenesis. The muscle-specific micro RNA (miR)-204 is known to be depleted in diseased pulmonary artery smooth muscle cells (PASMCs), furthering proliferation and promoting PH. Alterations of circulating plasma miR-204 across the trans-pulmonary vascular bed might provide mechanistic insights into the observed intracellular depletion and may help distinguish PH subtypes. MiR-204 levels were quantified at sequential pulmonary vasculature sites in 91 patients with World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH) (n = 47), Group II PH (n = 22), or no PH (n = 22). Blood from the right atrium/superior vena cava, pulmonary artery, and pulmonary capillary wedge was collected. Peripheral blood mononuclear cells (PBMCs) were isolated (n = 5/group). Excretion of miR-204 by PAH-PASMCs was also quantified in vitro. In Group I patients only, miR-204 concentration increased sequentially along the pulmonary vasculature (log fold-change slope = 0.22 [95% CI = 0.06–0.37], P = 0.008). PBMCs revealed insignificant miR-204 variations among PH groups (P = 0.12). Cultured PAH-PAMSCs displayed a decrease of intracellular miR-204 (P = 0.0004), and a converse increase of extracellular miR-204 (P = 0.0018) versus control. The stepwise elevation of circulating miR-204 across the pulmonary vasculature in Group I, but not Group II, PH indicates differences in muscle-specific pathobiology between subtypes. Considering the known importance of miR-204 in PH, these findings may suggest pathologic excretion of miR-204 in Group I PAH by PASMCs, thereby accounting for decreased intracellular miR-204 concentration. |
format | Online Article Text |
id | pubmed-6440051 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-64400512019-04-03 Distinct plasma gradients of microRNA-204 in the pulmonary circulation of patients suffering from WHO Groups I and II pulmonary hypertension Estephan, Leonard E. Genuardi, Michael V. Kosanovich, Chad M. Risbano, Michael G. Zhang, Yingze Petro, Nancy Watson, Annie Al Aaraj, Yassmin Sembrat, John C. Rojas, Mauricio Goncharov, Dmitry A. Simon, Marc A. Goncharova, Elena A. Vaidya, Anjali Smith, Akaya Mazurek, Jeremy Han, Yuchi Chan, Stephen Y. Pulm Circ Research Article Pulmonary hypertension (PH), a heterogeneous vascular disease, consists of subtypes with overlapping clinical phenotypes. MicroRNAs, small non-coding RNAs that negatively regulate gene expression, have emerged as regulators of PH pathogenesis. The muscle-specific micro RNA (miR)-204 is known to be depleted in diseased pulmonary artery smooth muscle cells (PASMCs), furthering proliferation and promoting PH. Alterations of circulating plasma miR-204 across the trans-pulmonary vascular bed might provide mechanistic insights into the observed intracellular depletion and may help distinguish PH subtypes. MiR-204 levels were quantified at sequential pulmonary vasculature sites in 91 patients with World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH) (n = 47), Group II PH (n = 22), or no PH (n = 22). Blood from the right atrium/superior vena cava, pulmonary artery, and pulmonary capillary wedge was collected. Peripheral blood mononuclear cells (PBMCs) were isolated (n = 5/group). Excretion of miR-204 by PAH-PASMCs was also quantified in vitro. In Group I patients only, miR-204 concentration increased sequentially along the pulmonary vasculature (log fold-change slope = 0.22 [95% CI = 0.06–0.37], P = 0.008). PBMCs revealed insignificant miR-204 variations among PH groups (P = 0.12). Cultured PAH-PAMSCs displayed a decrease of intracellular miR-204 (P = 0.0004), and a converse increase of extracellular miR-204 (P = 0.0018) versus control. The stepwise elevation of circulating miR-204 across the pulmonary vasculature in Group I, but not Group II, PH indicates differences in muscle-specific pathobiology between subtypes. Considering the known importance of miR-204 in PH, these findings may suggest pathologic excretion of miR-204 in Group I PAH by PASMCs, thereby accounting for decreased intracellular miR-204 concentration. SAGE Publications 2019-03-11 /pmc/articles/PMC6440051/ /pubmed/30854934 http://dx.doi.org/10.1177/2045894019840646 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Research Article Estephan, Leonard E. Genuardi, Michael V. Kosanovich, Chad M. Risbano, Michael G. Zhang, Yingze Petro, Nancy Watson, Annie Al Aaraj, Yassmin Sembrat, John C. Rojas, Mauricio Goncharov, Dmitry A. Simon, Marc A. Goncharova, Elena A. Vaidya, Anjali Smith, Akaya Mazurek, Jeremy Han, Yuchi Chan, Stephen Y. Distinct plasma gradients of microRNA-204 in the pulmonary circulation of patients suffering from WHO Groups I and II pulmonary hypertension |
title | Distinct plasma gradients of microRNA-204 in the pulmonary circulation of patients suffering from WHO Groups I and II pulmonary hypertension |
title_full | Distinct plasma gradients of microRNA-204 in the pulmonary circulation of patients suffering from WHO Groups I and II pulmonary hypertension |
title_fullStr | Distinct plasma gradients of microRNA-204 in the pulmonary circulation of patients suffering from WHO Groups I and II pulmonary hypertension |
title_full_unstemmed | Distinct plasma gradients of microRNA-204 in the pulmonary circulation of patients suffering from WHO Groups I and II pulmonary hypertension |
title_short | Distinct plasma gradients of microRNA-204 in the pulmonary circulation of patients suffering from WHO Groups I and II pulmonary hypertension |
title_sort | distinct plasma gradients of microrna-204 in the pulmonary circulation of patients suffering from who groups i and ii pulmonary hypertension |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440051/ https://www.ncbi.nlm.nih.gov/pubmed/30854934 http://dx.doi.org/10.1177/2045894019840646 |
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