Cilostazol attenuates vascular inflammation via the regulation of TICAM1/IRF3 signaling pathway

Area of Science:

• Cardiovascular Science
• Molecular Biology
• Pharmacology

Background:

• Atherosclerotic cardiovascular disease (ASCVD) is a major global health concern.
• Chronic endothelial inflammation is central to ASCVD pathogenesis.
• Identifying pro-atherogenic genes and therapeutic agents for vascular inflammation is crucial.

Purpose of the Study:

• To identify genes involved in vascular inflammation and screen for potential therapeutic drugs.
• To investigate the anti-inflammatory and anti-atherosclerotic effects of cilostazol.

Main Methods:

• Gene expression analysis in lipopolysaccharide (LPS)-induced vascular inflammation.
• In vitro and in vivo experiments assessing cilostazol's effects on inflammation, autophagy, necroptosis, inflammasome activation, and adhesion molecules.
• Evaluation of cilostazol's impact on aortic wall thickening in a mouse model.

Main Results:

• TICAM1 and IRF3 gene expression was upregulated in LPS-induced vascular inflammation.
• Cilostazol emerged as a potential drug targeting TICAM1.
• Cilostazol reduced inflammation, inflammasome activation (NLRP3/NLRP6), and interleukin-1β.
• Cilostazol attenuated TNF-α-induced adhesion molecule elevation and aortic wall thickening in mice.

Conclusions:

• Cilostazol demonstrates potential in reducing vascular inflammation and possibly inhibiting atherosclerosis progression.
• The findings provide evidence for cilostazol's therapeutic application in ASCVD.
• Further clinical trials are needed to confirm cilostazol's efficacy and safety in ASCVD patients.