Targeting Rac1 for the prevention of atherosclerosis among U.S. Veterans with inflammatory bowel disease

Small GTPases. 2022 Jan;13(1):205-210. doi: 10.1080/21541248.2021.1954863. Epub 2021 Jul 28.

Abstract

Evidence suggests that Ras-related C3 botulinum toxin substrate 1 (Rac1) might be a target in atherosclerotic disease (AD). We hypothesize that due to their ability to inhibit Rac1, thiopurines are associated with a lower risk of AD. We fit a time-dependent cox proportional hazards model estimating the hazard of AD among a national cohort of US veterans with inflammatory bowel disease. Patients exposed to thiopurines had a 7.5% lower risk of AD (HR = 0.925; 95% CI = (0.87-0.984)) compared to controls. The propensity score weighted analysis reveals thiopurine exposure reduces the risk of AD by 6.6% (HR = 0.934; 95% CI = (0.896-0.975)), compared to controls. Further exploration and evaluation of Rac1 inhibition as a target for AD is warranted.

Keywords: Rac1; atherosclerosis; cohort; inflammatory bowel disease; thiopurines.

MeSH terms

  • Atherosclerosis* / complications
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / prevention & control
  • Cohort Studies
  • Humans
  • Immunosuppressive Agents
  • Inflammatory Bowel Diseases* / complications
  • Inflammatory Bowel Diseases* / drug therapy
  • Veterans*
  • rac1 GTP-Binding Protein

Substances

  • Immunosuppressive Agents
  • RAC1 protein, human
  • rac1 GTP-Binding Protein