Differential Expression of Renin-Angiotensin System-related Components in Patients with Rheumatoid Arthritis and Osteoarthritis

Am J Med Sci. 2020 Jan;359(1):17-26. doi: 10.1016/j.amjms.2019.10.014. Epub 2019 Nov 5.

Abstract

Background: The purpose of this study was to demonstrate the role of renin-angiotensin system (RAS)-related components, vascular endothelial growth factor (VEGF) and atrial metalloproteinase-13 (MMP-13) in synovial tissue and synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).

Materials and methods: Thirty-four patients with RA and 41 patients with OA were included in the study. Renin, angiotensin-converting enzyme (ACE), VEGF and MMP-13 protein levels in the synovial fluid were measured by enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction analysis, western blot analysis and immunohistochemistry were used to quantify renin, ACE, angiotensin type 1 and type 2 receptors, VEGF and MMP-13 in OA and RA. Additionally, the correlation was determined by Pearson's coefficient.

Results: In synovial fluid, expression levels of renin, ACE, VEGF and MMP-13 in patients with RA were significantly higher than those in patients with OA. In synovial tissue, the RAS components VEGF and MMP-13 were also elevated in patients with RA. The results of immunohistochemistry in synovial tissue also showed that the RAS components VEGF and MMP-13 were significantly increased in patients with RA. Notably, the Pearson coefficient demonstrated that the levels of the RAS components were positively correlated with the expression of VEGF and MMP-13 in OA and RA.

Conclusions: The present results suggest that RAS-related components in RA and OA, including renin, ACE, angiotensin type 1 and type 2 receptors, are associated with increased expression of VEGF and play an important role in angiogenesis. Furthermore, there was a significant positive correlation between the expression of VEGF and MMP-13.

Keywords: MMP-13; Osteoarthritis; RAS-related components; Rheumatoid arthritis; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / metabolism*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Middle Aged
  • Osteoarthritis / complications
  • Osteoarthritis / metabolism*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 2 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism
  • Renin / genetics
  • Renin / metabolism
  • Renin-Angiotensin System / physiology*
  • Synovial Fluid / chemistry
  • Synovial Fluid / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Vascular Endothelial Growth Factor A
  • Peptidyl-Dipeptidase A
  • Renin
  • Matrix Metalloproteinase 13