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

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
• thiopurines
• atherosclerosis
• cohort
• inflammatory bowel disease

Acknowledgments

No funding agency had a role in study design or conduct, data collection, analysis, interpretation, or manuscript writing. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the US Department of Veterans Affairs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. This paper represents original research conducted using data from the Department of Veterans Affairs and is, in part, the result of work supported with resources and the use of facilities at the Dorn Research Institute, Columbia VA Health Care System, Columbia, South Carolina.

Disclosure statement

S.S.S. has received research grants from Boehringer Ingelheim, Gilead Sciences, Portola Pharmaceuticals, and United Therapeutics unrelated to this work. Other authors declare no competing interests.

Data availability statement

Analyses of the Veterans Health Administration Database were performed using data within the US Department of Veterans Affairs secure research environment, the VA Informatics and Computing Infrastructure (VINCI) and cannot be extracted. All relevant data outputs are within the paper.

Supplementary material

Supplemental data for this article can be accessed here