Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis

Abstract

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.

Proteomics discovery in children and young adults with HIV identifies fibrosis, inflammatory, and immune biomarkers associated with myocardial impairment

“…To our knowledge, this is the first study showing a link between higher EN-RAGE concentrations and abnormal cardiac function. Higher concentrations of VSIG2, a protein involved in lipid metabolism, have previously been associated with coronary artery disease in patients with rheumatoid arthritis and obstructive pulmonary disease [28][29][30]. Interestingly, VSIG2 was the only of the four proteins that appeared to be inversely associated with an abnormal MPI, such that higher concentrations of VSIG2 were observed in individuals with a normal vs. abnormal MPI.…”

The Role of CCL3 in the Pathogenesis of Rheumatoid Arthritis

“…Sun et al have shown that B cells affect osteoblast differentiation through a high expression of CCL3 and proinflammatory factors which further inhibit bone formation in RA [10]. Based on protein-protein interactions (PPI) showing a network of 43 CVD-related biomarkers, CCL3 was identified as increased in patients with RA and periodontal disease [11]. Those findings provide vivid evidence for the role of CCL3 in the pathogenesis and immune regulation of RA.…”

Inflammatory response in traumatic brain and spinal cord injury: The role of XCL1‐XCR1 axis and T cells

“…In patients with rheumatoid arthritis, XCL1 manifests itself in the synovium, while XCR1 is a characteristic feature of infiltrating mononuclear and synovial cells. 78 Furthermore, increased expression of XCL1 has been observed in tissues affected by Crohn's disease and in inflammatory responses of diabetic mice. 79 , 80 These findings collectively suggest that the expression of XCL1 and XCR1 increases in various sterile inflammatory diseases in humans and mice.…”

“…In particular, the XCL1‐XCR1 axis plays a significant role in the pathogenesis of rheumatoid arthritis by inducing Th1‐mediated pro‐inflammatory responses. In patients with rheumatoid arthritis, XCL1 manifests itself in the synovium, while XCR1 is a characteristic feature of infiltrating mononuclear and synovial cells 78 . Furthermore, increased expression of XCL1 has been observed in tissues affected by Crohn's disease and in inflammatory responses of diabetic mice 79,80 .…”