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

S Scott Sutton1,2, Joseph Magagnoli1,2, Tammy H Cummings1,2

  • 1Dorn Research Institute, Columbia VA Health Care System, Columbia, SC, USA.

Small Gtpases
|July 29, 2021
PubMed

Insights

Thiopurines may lower the risk of atherosclerotic disease (AD) by inhibiting Ras-related C3 botulinum toxin substrate 1 (Rac1). This study found thiopurine use associated with reduced AD risk in US veterans.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Immunology

Background:

  • Ras-related C3 botulinum toxin substrate 1 (Rac1) is implicated in atherosclerotic disease (AD) pathogenesis.
  • Thiopurines are known to inhibit Rac1 activity.
  • A potential link between thiopurine use and reduced AD risk warrants investigation.

Purpose of the Study:

  • To investigate the association between thiopurine exposure and the risk of developing atherosclerotic disease (AD).
  • To evaluate the potential of Rac1 inhibition as a therapeutic target for AD.

Main Methods:

  • A time-dependent Cox proportional hazards model was employed.
  • Analysis was conducted on a national cohort of US veterans diagnosed with inflammatory bowel disease.
  • Propensity score weighting was utilized to control for confounding factors.

Main Results:

  • Thiopurine exposure was associated with a 7.5% lower risk of AD (HR=0.925; 95% CI [0.87-0.984]) in the initial analysis.
  • Propensity score weighted analysis indicated a 6.6% reduction in AD risk (HR=0.934; 95% CI [0.896-0.975]) with thiopurine exposure.
  • These findings suggest a protective effect of thiopurines against AD.

Conclusions:

  • Thiopurine use is associated with a reduced risk of atherosclerotic disease.
  • Rac1 inhibition represents a promising therapeutic target for managing AD.
  • Further research is recommended to explore Rac1's role in AD and the clinical utility of thiopurines.
Keywords:
Rac1atherosclerosiscohortinflammatory bowel diseasethiopurines

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