Cargando…

Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis

Objectives: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine...

Descripción completa

Detalles Bibliográficos
Autores principales: Panezai, Jeneen, Ghaffar, Ambereen, Altamash, Mohammad, Åberg, Mikael, Van Dyke, Thomas E., Larsson, Anders, Engström, Per-Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945365/
https://www.ncbi.nlm.nih.gov/pubmed/35327515
http://dx.doi.org/10.3390/biomedicines10030714
_version_ 1784673941420244992
author Panezai, Jeneen
Ghaffar, Ambereen
Altamash, Mohammad
Åberg, Mikael
Van Dyke, Thomas E.
Larsson, Anders
Engström, Per-Erik
author_facet Panezai, Jeneen
Ghaffar, Ambereen
Altamash, Mohammad
Åberg, Mikael
Van Dyke, Thomas E.
Larsson, Anders
Engström, Per-Erik
author_sort Panezai, Jeneen
collection PubMed
description Objectives: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine CVD risk, alterations at the molecular level need to be identified. The objective of this study, therefore, was to assess the relationship of CVD associated biomarkers in RA patients and how it is influenced by PD. Methods: The study consisted of patient (26 RA with PD, 21 RA without PD, 51 patients with PD only) and systemically and periodontally healthy control (n = 20) groups. Periodontal parameters bleeding on probing, probing pocket depth, and marginal bone loss were determined to characterize the patient groups. Proteomic analysis of 92 CVD-related protein biomarkers was performed using a multiplex proximity extension assay. Biomarkers were clustered using the search tool for retrieval of interacting genes (STRING) to determine protein–protein interaction (PPI) networks. Results: RA patients with PD had higher detection levels for 47% of the measured markers (ANGPT1, BOC, CCL17, CCL3, CD4, CD84, CTRC, FGF-21, FGF-23, GLO1, HAOX1, HB-EGF, hOSCAR, HSP 27, IL16, IL-17D, IL18, IL-27, IL6, LEP, LPL, MERTK, MMP12, MMP7, NEMO, PAPPA, PAR-1, PARP-1, PD-L2, PGF, PIgR, PRELP, RAGE, SCF, SLAMF7, SRC, THBS2, THPO, TNFRSF13B, TRAIL-R2, VEGFD, VSIG2, and XCL1) as compared to RA without PD. Furthermore, a strong biological network was identified amongst these proteins (clustering coefficient = 0.52, PPI enrichment p-value < 0.0001). Coefficients for protein clusters involved in CVD (0.59), metabolic (0.53), and skeletal (0.51) diseases were strongest in the PD group. Conclusion: Periodontal disease augments CVD-related biomarkers in RA through shared pathological clusters, concurrently enhancing metabolic and skeletal disease protein interactions, independent of autoimmune status.
format Online
Article
Text
id pubmed-8945365
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89453652022-03-25 Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis Panezai, Jeneen Ghaffar, Ambereen Altamash, Mohammad Åberg, Mikael Van Dyke, Thomas E. Larsson, Anders Engström, Per-Erik Biomedicines Article Objectives: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine CVD risk, alterations at the molecular level need to be identified. The objective of this study, therefore, was to assess the relationship of CVD associated biomarkers in RA patients and how it is influenced by PD. Methods: The study consisted of patient (26 RA with PD, 21 RA without PD, 51 patients with PD only) and systemically and periodontally healthy control (n = 20) groups. Periodontal parameters bleeding on probing, probing pocket depth, and marginal bone loss were determined to characterize the patient groups. Proteomic analysis of 92 CVD-related protein biomarkers was performed using a multiplex proximity extension assay. Biomarkers were clustered using the search tool for retrieval of interacting genes (STRING) to determine protein–protein interaction (PPI) networks. Results: RA patients with PD had higher detection levels for 47% of the measured markers (ANGPT1, BOC, CCL17, CCL3, CD4, CD84, CTRC, FGF-21, FGF-23, GLO1, HAOX1, HB-EGF, hOSCAR, HSP 27, IL16, IL-17D, IL18, IL-27, IL6, LEP, LPL, MERTK, MMP12, MMP7, NEMO, PAPPA, PAR-1, PARP-1, PD-L2, PGF, PIgR, PRELP, RAGE, SCF, SLAMF7, SRC, THBS2, THPO, TNFRSF13B, TRAIL-R2, VEGFD, VSIG2, and XCL1) as compared to RA without PD. Furthermore, a strong biological network was identified amongst these proteins (clustering coefficient = 0.52, PPI enrichment p-value < 0.0001). Coefficients for protein clusters involved in CVD (0.59), metabolic (0.53), and skeletal (0.51) diseases were strongest in the PD group. Conclusion: Periodontal disease augments CVD-related biomarkers in RA through shared pathological clusters, concurrently enhancing metabolic and skeletal disease protein interactions, independent of autoimmune status. MDPI 2022-03-19 /pmc/articles/PMC8945365/ /pubmed/35327515 http://dx.doi.org/10.3390/biomedicines10030714 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Panezai, Jeneen
Ghaffar, Ambereen
Altamash, Mohammad
Åberg, Mikael
Van Dyke, Thomas E.
Larsson, Anders
Engström, Per-Erik
Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis
title Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis
title_full Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis
title_fullStr Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis
title_full_unstemmed Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis
title_short Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis
title_sort periodontal disease augments cardiovascular disease risk biomarkers in rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945365/
https://www.ncbi.nlm.nih.gov/pubmed/35327515
http://dx.doi.org/10.3390/biomedicines10030714
work_keys_str_mv AT panezaijeneen periodontaldiseaseaugmentscardiovasculardiseaseriskbiomarkersinrheumatoidarthritis
AT ghaffarambereen periodontaldiseaseaugmentscardiovasculardiseaseriskbiomarkersinrheumatoidarthritis
AT altamashmohammad periodontaldiseaseaugmentscardiovasculardiseaseriskbiomarkersinrheumatoidarthritis
AT abergmikael periodontaldiseaseaugmentscardiovasculardiseaseriskbiomarkersinrheumatoidarthritis
AT vandykethomase periodontaldiseaseaugmentscardiovasculardiseaseriskbiomarkersinrheumatoidarthritis
AT larssonanders periodontaldiseaseaugmentscardiovasculardiseaseriskbiomarkersinrheumatoidarthritis
AT engstrompererik periodontaldiseaseaugmentscardiovasculardiseaseriskbiomarkersinrheumatoidarthritis