MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors
Background: Pulmonary arterial hypertension (PAH) is a major cause of death in systemic sclerosis (SSc). Early detection may improve patient outcomes. Methods: We searched for circulating miRNAs that would constitute biomarkers in SSc patients with PAH (SSc-PAH). We compared miRNA levels and laborat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/3/629 |
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| author | Mor Zaaroor Levy Noa Rabinowicz Maia Yamila Kohon Avshalom Shalom Ariel Berl Tzipi Hornik-Lurie Liat Drucker Shelly Tartakover Matalon Yair Levy |
| author_facet | Mor Zaaroor Levy Noa Rabinowicz Maia Yamila Kohon Avshalom Shalom Ariel Berl Tzipi Hornik-Lurie Liat Drucker Shelly Tartakover Matalon Yair Levy |
| author_sort | Mor Zaaroor Levy |
| collection | DOAJ |
| description | Background: Pulmonary arterial hypertension (PAH) is a major cause of death in systemic sclerosis (SSc). Early detection may improve patient outcomes. Methods: We searched for circulating miRNAs that would constitute biomarkers in SSc patients with PAH (SSc-PAH). We compared miRNA levels and laboratory parameters while evaluating miRNA levels in white blood cells (WBCs) and myofibroblasts. Results: Our study found: 1) miR-26 and miR-let-7d levels were significantly lower in SSc-PAH (<i>n</i> = 12) versus SSc without PAH (SSc-noPAH) patients (<i>n</i> = 25); 2) a positive correlation between miR-26 and miR-let-7d and complement-C3; 3) GO-annotations of genes that are miR-26/miR-let-7d targets and that are expressed in myofibroblast cells, suggesting that these miRNAs regulate the TGF-β-pathway; 4) reduced levels of both miRNAs accompanied fibroblast differentiation to myofibroblasts, while macitentan (endothelin receptor-antagonist) increased the levels. WBCs of SSc-noPAH and SSc-PAH patients contained equal amounts of miR-26/miR-let-7d. During the study, an echocardiograph that predicted PAH development, showed increased pulmonary artery pressure in three SSc-noPAH patients. At study initiation, those patients and an additional SSc-noPAH patient, who eventually developed PAH, had miR-let-7d/miR-26 levels similar to those of SSc-PAH patients. This implies that reduced miR-let-7d/miR-26 levels might be an early indication of PAH. Conclusions: miR-26 and miR-let-7d may be serological markers for SSc-PAH. The results of our study suggest their involvement in myofibroblast differentiation and complement pathway activation, both of which are active in PAH development. |
| first_indexed | 2024-03-09T20:05:26Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:05:26Z |
| publishDate | 2022-03-01 |
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| series | Biomedicines |
| spelling | doaj.art-0779d4b150fd47598d816c8bf5ad2e6e2023-11-24T00:33:01ZengMDPI AGBiomedicines2227-90592022-03-0110362910.3390/biomedicines10030629MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and EffectorsMor Zaaroor Levy0Noa Rabinowicz1Maia Yamila Kohon2Avshalom Shalom3Ariel Berl4Tzipi Hornik-Lurie5Liat Drucker6Shelly Tartakover Matalon7Yair Levy8Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelResearch Authority, Meir Medical Center, Kfar Saba 4428164, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelBackground: Pulmonary arterial hypertension (PAH) is a major cause of death in systemic sclerosis (SSc). Early detection may improve patient outcomes. Methods: We searched for circulating miRNAs that would constitute biomarkers in SSc patients with PAH (SSc-PAH). We compared miRNA levels and laboratory parameters while evaluating miRNA levels in white blood cells (WBCs) and myofibroblasts. Results: Our study found: 1) miR-26 and miR-let-7d levels were significantly lower in SSc-PAH (<i>n</i> = 12) versus SSc without PAH (SSc-noPAH) patients (<i>n</i> = 25); 2) a positive correlation between miR-26 and miR-let-7d and complement-C3; 3) GO-annotations of genes that are miR-26/miR-let-7d targets and that are expressed in myofibroblast cells, suggesting that these miRNAs regulate the TGF-β-pathway; 4) reduced levels of both miRNAs accompanied fibroblast differentiation to myofibroblasts, while macitentan (endothelin receptor-antagonist) increased the levels. WBCs of SSc-noPAH and SSc-PAH patients contained equal amounts of miR-26/miR-let-7d. During the study, an echocardiograph that predicted PAH development, showed increased pulmonary artery pressure in three SSc-noPAH patients. At study initiation, those patients and an additional SSc-noPAH patient, who eventually developed PAH, had miR-let-7d/miR-26 levels similar to those of SSc-PAH patients. This implies that reduced miR-let-7d/miR-26 levels might be an early indication of PAH. Conclusions: miR-26 and miR-let-7d may be serological markers for SSc-PAH. The results of our study suggest their involvement in myofibroblast differentiation and complement pathway activation, both of which are active in PAH development.https://www.mdpi.com/2227-9059/10/3/629systemic sclerosispulmonary arterial hypertension (PAH)biomarkersmiRNAcomplementmyofibroblasts |
| spellingShingle | Mor Zaaroor Levy Noa Rabinowicz Maia Yamila Kohon Avshalom Shalom Ariel Berl Tzipi Hornik-Lurie Liat Drucker Shelly Tartakover Matalon Yair Levy MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors Biomedicines systemic sclerosis pulmonary arterial hypertension (PAH) biomarkers miRNA complement myofibroblasts |
| title | MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors |
| title_full | MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors |
| title_fullStr | MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors |
| title_full_unstemmed | MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors |
| title_short | MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors |
| title_sort | mirnas in systemic sclerosis patients with pulmonary arterial hypertension markers and effectors |
| topic | systemic sclerosis pulmonary arterial hypertension (PAH) biomarkers miRNA complement myofibroblasts |
| url | https://www.mdpi.com/2227-9059/10/3/629 |
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