STAT4 contributes to adipose tissue inflammation and atherosclerosis

Area of Science:

• Immunology
• Cardiovascular Science
• Metabolic Disease Research

Background:

• Adipose tissue (AT) inflammation is increasingly recognized as a contributor to cardiovascular disease.
• Signal transducer and activator of transcription 4 (STAT4) plays a role in AT inflammation and insulin resistance in obesity.

Purpose of the Study:

• To investigate the impact of STAT4 deficiency on visceral and peri-aortic AT inflammation in a non-obese atherosclerosis model.
• To assess the role of STAT4 in immune cell infiltration and cytokine expression within AT during atherosclerosis development.

Main Methods:

• Utilized Stat4(-/-)Apoe(-/-) and Apoe(-/-) mice fed either a chow or Western diet for 12 weeks.
• Analyzed immune cell composition via flow cytometry and quantified cytokine/chemokine expression using real-time PCR in AT.
• Assessed atherosclerotic plaque burden in the aorta.

Main Results:

• Stat4(-/-)Apoe(-/-) and Apoe(-/-) mice exhibited similar body weight, glucose, and lipid profiles.
• Western diet increased immune cell infiltration in AT of Apoe(-/-) mice, but not in Stat4(-/-)Apoe(-/-) mice.
• STAT4 deficiency significantly reduced pro-inflammatory cytokines (IL12p40, TNFa, CCL5, CXCL10, CX3CL1) in peri-aortic AT.
• Stat4(-/-)Apoe(-/-) mice showed significantly reduced atherosclerotic plaque burden compared to controls.

Conclusions:

• STAT4 deletion attenuates AT inflammation and reduces atherosclerosis development, independent of obesity.
• Targeting STAT4 may offer a therapeutic strategy for cardiovascular disease by reducing AT inflammation.