Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/fphar.2021.648769 http://hdl.handle.net/11449/207868 |
Resumo: | Idiopathic pulmonary artery hypertension (IPAH), chronic thromboembolic pulmonary hypertension (CTEPH), and acute pulmonary embolism (APTE) are life-threatening cardiopulmonary diseases without specific surgical or medical treatment. Although APTE, CTEPH and IPAH are different pulmonary vascular diseases in terms of clinical presentation, prevalence, pathophysiology and prognosis, the identification of their circulating microRNA (miRNAs) might help in recognizing differences in their outcome evolution and clinical forms. The aim of this study was to describe the APTE, CTEPH, and IPAH-associated miRNAs and to predict their target genes. The target genes of the key differentially expressed miRNAs were analyzed, and functional enrichment analyses were carried out. The miRNAs were detected using RT-PCR. Finally, we incorporated plasma circulating miRNAs in baseline and clinical characteristics of the patients to detect differences between APTE and CTEPH in time of evolution, and differences between CTEPH and IPAH in diseases form. We found five top circulating plasma miRNAs in common with APTE, CTEPH and IPAH assembled in one conglomerate. Among them, miR-let-7i-5p expression was upregulated in APTE and IPAH, while miRNA-320a was upregulated in CTEP and IPAH. The network construction for target genes showed 11 genes regulated by let-7i-5p and 20 genes regulated by miR-320a, all of them regulators of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell, and pulmonary artery smooth muscle cells. AR (androgen receptor), a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in pathways in cancer, whereas PRKCA (Protein Kinase C Alpha), also a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in KEGG pathways, such as pathways in cancer, glioma, and PI3K-Akt signaling pathway. We inferred that CTEPH might be the consequence of abnormal remodeling in APTE, while unbalance between the hyperproliferative and apoptosis-resistant phenotype of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell and pulmonary artery smooth muscle cells in pulmonary artery confer differences in IPAH and CTEPH diseases form. We concluded that the incorporation of plasma circulating let-7i-5p and miRNA-320a in baseline and clinical characteristics of the patients reinforces differences between APTE and CTEPH in outcome evolution, as well as differences between CTEPH and IPAH in diseases form. |
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Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertensionblood plasmamicroRNApulmonary hypertensionRNA-sequencingthromboemboilc diseaseIdiopathic pulmonary artery hypertension (IPAH), chronic thromboembolic pulmonary hypertension (CTEPH), and acute pulmonary embolism (APTE) are life-threatening cardiopulmonary diseases without specific surgical or medical treatment. Although APTE, CTEPH and IPAH are different pulmonary vascular diseases in terms of clinical presentation, prevalence, pathophysiology and prognosis, the identification of their circulating microRNA (miRNAs) might help in recognizing differences in their outcome evolution and clinical forms. The aim of this study was to describe the APTE, CTEPH, and IPAH-associated miRNAs and to predict their target genes. The target genes of the key differentially expressed miRNAs were analyzed, and functional enrichment analyses were carried out. The miRNAs were detected using RT-PCR. Finally, we incorporated plasma circulating miRNAs in baseline and clinical characteristics of the patients to detect differences between APTE and CTEPH in time of evolution, and differences between CTEPH and IPAH in diseases form. We found five top circulating plasma miRNAs in common with APTE, CTEPH and IPAH assembled in one conglomerate. Among them, miR-let-7i-5p expression was upregulated in APTE and IPAH, while miRNA-320a was upregulated in CTEP and IPAH. The network construction for target genes showed 11 genes regulated by let-7i-5p and 20 genes regulated by miR-320a, all of them regulators of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell, and pulmonary artery smooth muscle cells. AR (androgen receptor), a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in pathways in cancer, whereas PRKCA (Protein Kinase C Alpha), also a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in KEGG pathways, such as pathways in cancer, glioma, and PI3K-Akt signaling pathway. We inferred that CTEPH might be the consequence of abnormal remodeling in APTE, while unbalance between the hyperproliferative and apoptosis-resistant phenotype of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell and pulmonary artery smooth muscle cells in pulmonary artery confer differences in IPAH and CTEPH diseases form. We concluded that the incorporation of plasma circulating let-7i-5p and miRNA-320a in baseline and clinical characteristics of the patients reinforces differences between APTE and CTEPH in outcome evolution, as well as differences between CTEPH and IPAH in diseases form.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Department of Pathology Laboratory of Histomorphometry and Lung Genomics Faculty of Medicine University of São PauloDepartment of Pathology and Legal Medicine Respiratory Medicine Laboratory Ribeirão Preto Medical School University of São Paulo (USP)Health Technology Assessment Center (NATS) Clinical Hospital (HCFMB) Medical School of São Paulo State University (UNESP)Laboratory of Molecular Genetics Center for Translational Research in Oncology Cancer Institute of São Paulo (ICESP)Bioinformatic Laboratory Institute of Chemistry University of São Paulo (USP)Pulmonary Hypertension Care Center Department of Internal Medicine Ribeirão Preto Medical School University of São Paulo (USP)Department of Biostatistics Plant Biology Parasitology and Zoology Institute of Biosciences São Paulo State University (UNESP)Department of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)Pulmonary Hypertension Care Center Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP)Laboratory of Pulmonary Investigation Carlos Chagas Filho Biophysics Institute Federal University of Rio de Janeiro Centro de Ciências da SaúdeNational Institute of Science and Technology for Regenerative MedicineDepartment of Radiology and Oncology Medical School of São Paulo State University (UNESP)Health Technology Assessment Center (NATS) Clinical Hospital (HCFMB) Medical School of São Paulo State University (UNESP)Department of Biostatistics Plant Biology Parasitology and Zoology Institute of Biosciences São Paulo State University (UNESP)Department of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)Pulmonary Hypertension Care Center Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP)Department of Radiology and Oncology Medical School of São Paulo State University (UNESP)Universidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Cancer Institute of São Paulo (ICESP)Centro de Ciências da SaúdeNational Institute of Science and Technology for Regenerative MedicineFabro, Alexandre TodorovicMachado-Rugolo, Juliana [UNESP]Baldavira, Camila MachadoPrieto, Tabatha GutierrezFarhat, CecíliaRotea ManGone, Flavia ReginaBatah, Sabrina SetembreCruvinel, Heloísa ResendeAldá, Maiara AlmeidaMonteiro, Jhonatas SirinoPádua, Adriana InacioMorais, Sirlei SianiAntônio de Oliveira, Rogério [UNESP]Santos, Marcel KoenigkamBaddini-Martinez, José AntônioSetubal, João CarlosRainho, Claudia Aparecida [UNESP]Yoo, Hugo Hyung Bok [UNESP]Silva, Pedro LemeNagai, Maria Aparecida [UNESP]Capelozzi, Vera Luiza2021-06-25T11:02:25Z2021-06-25T11:02:25Z2021-05-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fphar.2021.648769Frontiers in Pharmacology, v. 12.1663-9812http://hdl.handle.net/11449/20786810.3389/fphar.2021.6487692-s2.0-8510779507888148235451595040000-0002-0285-1162Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Pharmacologyinfo:eu-repo/semantics/openAccess2024-08-14T17:23:32Zoai:repositorio.unesp.br:11449/207868Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-14T17:23:32Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension |
title |
Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension |
spellingShingle |
Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension Fabro, Alexandre Todorovic blood plasma microRNA pulmonary hypertension RNA-sequencing thromboemboilc disease |
title_short |
Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension |
title_full |
Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension |
title_fullStr |
Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension |
title_full_unstemmed |
Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension |
title_sort |
Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension |
author |
Fabro, Alexandre Todorovic |
author_facet |
Fabro, Alexandre Todorovic Machado-Rugolo, Juliana [UNESP] Baldavira, Camila Machado Prieto, Tabatha Gutierrez Farhat, Cecília Rotea ManGone, Flavia Regina Batah, Sabrina Setembre Cruvinel, Heloísa Resende Aldá, Maiara Almeida Monteiro, Jhonatas Sirino Pádua, Adriana Inacio Morais, Sirlei Siani Antônio de Oliveira, Rogério [UNESP] Santos, Marcel Koenigkam Baddini-Martinez, José Antônio Setubal, João Carlos Rainho, Claudia Aparecida [UNESP] Yoo, Hugo Hyung Bok [UNESP] Silva, Pedro Leme Nagai, Maria Aparecida [UNESP] Capelozzi, Vera Luiza |
author_role |
author |
author2 |
Machado-Rugolo, Juliana [UNESP] Baldavira, Camila Machado Prieto, Tabatha Gutierrez Farhat, Cecília Rotea ManGone, Flavia Regina Batah, Sabrina Setembre Cruvinel, Heloísa Resende Aldá, Maiara Almeida Monteiro, Jhonatas Sirino Pádua, Adriana Inacio Morais, Sirlei Siani Antônio de Oliveira, Rogério [UNESP] Santos, Marcel Koenigkam Baddini-Martinez, José Antônio Setubal, João Carlos Rainho, Claudia Aparecida [UNESP] Yoo, Hugo Hyung Bok [UNESP] Silva, Pedro Leme Nagai, Maria Aparecida [UNESP] Capelozzi, Vera Luiza |
author2_role |
author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) Cancer Institute of São Paulo (ICESP) Centro de Ciências da Saúde National Institute of Science and Technology for Regenerative Medicine |
dc.contributor.author.fl_str_mv |
Fabro, Alexandre Todorovic Machado-Rugolo, Juliana [UNESP] Baldavira, Camila Machado Prieto, Tabatha Gutierrez Farhat, Cecília Rotea ManGone, Flavia Regina Batah, Sabrina Setembre Cruvinel, Heloísa Resende Aldá, Maiara Almeida Monteiro, Jhonatas Sirino Pádua, Adriana Inacio Morais, Sirlei Siani Antônio de Oliveira, Rogério [UNESP] Santos, Marcel Koenigkam Baddini-Martinez, José Antônio Setubal, João Carlos Rainho, Claudia Aparecida [UNESP] Yoo, Hugo Hyung Bok [UNESP] Silva, Pedro Leme Nagai, Maria Aparecida [UNESP] Capelozzi, Vera Luiza |
dc.subject.por.fl_str_mv |
blood plasma microRNA pulmonary hypertension RNA-sequencing thromboemboilc disease |
topic |
blood plasma microRNA pulmonary hypertension RNA-sequencing thromboemboilc disease |
description |
Idiopathic pulmonary artery hypertension (IPAH), chronic thromboembolic pulmonary hypertension (CTEPH), and acute pulmonary embolism (APTE) are life-threatening cardiopulmonary diseases without specific surgical or medical treatment. Although APTE, CTEPH and IPAH are different pulmonary vascular diseases in terms of clinical presentation, prevalence, pathophysiology and prognosis, the identification of their circulating microRNA (miRNAs) might help in recognizing differences in their outcome evolution and clinical forms. The aim of this study was to describe the APTE, CTEPH, and IPAH-associated miRNAs and to predict their target genes. The target genes of the key differentially expressed miRNAs were analyzed, and functional enrichment analyses were carried out. The miRNAs were detected using RT-PCR. Finally, we incorporated plasma circulating miRNAs in baseline and clinical characteristics of the patients to detect differences between APTE and CTEPH in time of evolution, and differences between CTEPH and IPAH in diseases form. We found five top circulating plasma miRNAs in common with APTE, CTEPH and IPAH assembled in one conglomerate. Among them, miR-let-7i-5p expression was upregulated in APTE and IPAH, while miRNA-320a was upregulated in CTEP and IPAH. The network construction for target genes showed 11 genes regulated by let-7i-5p and 20 genes regulated by miR-320a, all of them regulators of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell, and pulmonary artery smooth muscle cells. AR (androgen receptor), a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in pathways in cancer, whereas PRKCA (Protein Kinase C Alpha), also a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in KEGG pathways, such as pathways in cancer, glioma, and PI3K-Akt signaling pathway. We inferred that CTEPH might be the consequence of abnormal remodeling in APTE, while unbalance between the hyperproliferative and apoptosis-resistant phenotype of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell and pulmonary artery smooth muscle cells in pulmonary artery confer differences in IPAH and CTEPH diseases form. We concluded that the incorporation of plasma circulating let-7i-5p and miRNA-320a in baseline and clinical characteristics of the patients reinforces differences between APTE and CTEPH in outcome evolution, as well as differences between CTEPH and IPAH in diseases form. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T11:02:25Z 2021-06-25T11:02:25Z 2021-05-28 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fphar.2021.648769 Frontiers in Pharmacology, v. 12. 1663-9812 http://hdl.handle.net/11449/207868 10.3389/fphar.2021.648769 2-s2.0-85107795078 8814823545159504 0000-0002-0285-1162 |
url |
http://dx.doi.org/10.3389/fphar.2021.648769 http://hdl.handle.net/11449/207868 |
identifier_str_mv |
Frontiers in Pharmacology, v. 12. 1663-9812 10.3389/fphar.2021.648769 2-s2.0-85107795078 8814823545159504 0000-0002-0285-1162 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers in Pharmacology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808128165911986176 |