Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study

<b>Background:</b> Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with an increased risk of cardiovascular disease (CVD), largely driven by peripheral endothelial dysfunction (ED). Humanin, a mitochondrial-derived peptide, has been suggested to play a protective ro...

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Main Authors: Donatella Coradduzza, Sara Cruciani, Biagio Di Lorenzo, Maria Rosaria De Miglio, Angelo Zinellu, Margherita Maioli, Serenella Medici, Gian Luca Erre, Ciriaco Carru
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Non-Coding RNA
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Online Access:https://www.mdpi.com/2311-553X/11/1/5
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author Donatella Coradduzza
Sara Cruciani
Biagio Di Lorenzo
Maria Rosaria De Miglio
Angelo Zinellu
Margherita Maioli
Serenella Medici
Gian Luca Erre
Ciriaco Carru
author_facet Donatella Coradduzza
Sara Cruciani
Biagio Di Lorenzo
Maria Rosaria De Miglio
Angelo Zinellu
Margherita Maioli
Serenella Medici
Gian Luca Erre
Ciriaco Carru
author_sort Donatella Coradduzza
collection DOAJ
description <b>Background:</b> Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with an increased risk of cardiovascular disease (CVD), largely driven by peripheral endothelial dysfunction (ED). Humanin, a mitochondrial-derived peptide, has been suggested to play a protective role in endothelial function. However, the relationship between Humanin levels and ED in RA, as well as the interaction between Humanin and non-coding RNAs such as Long Non-Coding RNA GAS5, microRNA-21 (miR-21), and microRNA-103 (miR-103), remains unclear. <b>Objective:</b> This study aimed to investigate the relationship between circulating Humanin levels, non-coding RNAs (GAS5, miR-21, miR-103), and endothelial dysfunction (ED) in patients with RA. Additionally, we explored the correlation between Humanin expression and specific non-coding RNAs (GAS5, miR-21, and miR-103) to better understand their potential role in vascular health. <b>Methods:</b> Peripheral ED was assessed using flow-mediated pulse amplitude tonometry, with Ln-RHI values <0.51 indicating dysfunction. Humanin levels, GAS5, miR-21, and miR-103 were measured in RA patients. Univariate and multivariate analyses were conducted to determine the relationship between these biomarkers and ED. Kaplan–Meier survival analysis and ROC curve analysis were used to assess the prognostic value of Humanin. <b>Results:</b> Higher Humanin levels were significantly associated with better endothelial function (OR = 0.9774, <i>p</i> = 0.0196). Kaplan–Meier analysis demonstrated that higher Humanin levels correlated with improved survival (<i>p</i> < 0.0001). The non-coding RNAs (GAS5, miR-21, and miR-103) did not show significant associations with ED. <b>Conclusions:</b> Humanin is a potential protective biomarker for endothelial dysfunction and survival in RA patients. Further research is needed to explore the interaction between Humanin and non-coding RNAs in the context of vascular health.
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spelling doaj-art-5a6cfb5e711c42599f5eeca5542bc7b42025-08-20T02:44:56ZengMDPI AGNon-Coding RNA2311-553X2025-01-01111510.3390/ncrna11010005Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot StudyDonatella Coradduzza0Sara Cruciani1Biagio Di Lorenzo2Maria Rosaria De Miglio3Angelo Zinellu4Margherita Maioli5Serenella Medici6Gian Luca Erre7Ciriaco Carru8Department of Biomedical Sciences, University of Sassari, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, 07100 Sassari, ItalyDepartment of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, 07100 Sassari, ItalyDepartment of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, 07100 Sassari, ItalyDepartment of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy<b>Background:</b> Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with an increased risk of cardiovascular disease (CVD), largely driven by peripheral endothelial dysfunction (ED). Humanin, a mitochondrial-derived peptide, has been suggested to play a protective role in endothelial function. However, the relationship between Humanin levels and ED in RA, as well as the interaction between Humanin and non-coding RNAs such as Long Non-Coding RNA GAS5, microRNA-21 (miR-21), and microRNA-103 (miR-103), remains unclear. <b>Objective:</b> This study aimed to investigate the relationship between circulating Humanin levels, non-coding RNAs (GAS5, miR-21, miR-103), and endothelial dysfunction (ED) in patients with RA. Additionally, we explored the correlation between Humanin expression and specific non-coding RNAs (GAS5, miR-21, and miR-103) to better understand their potential role in vascular health. <b>Methods:</b> Peripheral ED was assessed using flow-mediated pulse amplitude tonometry, with Ln-RHI values <0.51 indicating dysfunction. Humanin levels, GAS5, miR-21, and miR-103 were measured in RA patients. Univariate and multivariate analyses were conducted to determine the relationship between these biomarkers and ED. Kaplan–Meier survival analysis and ROC curve analysis were used to assess the prognostic value of Humanin. <b>Results:</b> Higher Humanin levels were significantly associated with better endothelial function (OR = 0.9774, <i>p</i> = 0.0196). Kaplan–Meier analysis demonstrated that higher Humanin levels correlated with improved survival (<i>p</i> < 0.0001). The non-coding RNAs (GAS5, miR-21, and miR-103) did not show significant associations with ED. <b>Conclusions:</b> Humanin is a potential protective biomarker for endothelial dysfunction and survival in RA patients. Further research is needed to explore the interaction between Humanin and non-coding RNAs in the context of vascular health.https://www.mdpi.com/2311-553X/11/1/5biomarkershumaninmiRNAlong non-coding RNAcardiovascular riskendothelial dysfunction
spellingShingle Donatella Coradduzza
Sara Cruciani
Biagio Di Lorenzo
Maria Rosaria De Miglio
Angelo Zinellu
Margherita Maioli
Serenella Medici
Gian Luca Erre
Ciriaco Carru
Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study
Non-Coding RNA
biomarkers
humanin
miRNA
long non-coding RNA
cardiovascular risk
endothelial dysfunction
title Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study
title_full Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study
title_fullStr Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study
title_full_unstemmed Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study
title_short Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study
title_sort plasma humanin and non coding rnas as biomarkers of endothelial dysfunction in rheumatoid arthritis a pilot study
topic biomarkers
humanin
miRNA
long non-coding RNA
cardiovascular risk
endothelial dysfunction
url https://www.mdpi.com/2311-553X/11/1/5
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