Caspase-1 deficiency decreases atherosclerosis in apolipoprotein E-null mice

Area of Science:

• Immunology
• Cardiovascular Biology
• Molecular Medicine

Background:

• Caspase-1 is a key protease in mammalian immunity, activating pro-inflammatory cytokines like IL-1β and IL-18.
• Atherosclerosis is a chronic inflammatory disease of the arteries.

Purpose of the Study:

• To investigate the role of caspase-1 in the development of atherosclerosis.
• To determine if the absence of caspase-1 can protect against atherosclerosis in apolipoprotein E-null mice.

Main Methods:

• Apolipoprotein E-null mice with or without a functional caspase-1 gene were fed either a low-fat or a high-fat diet.
• Atherosclerosis was quantified in the aortic sinus and arch.
• Immune cell activation markers, MHC class II and IFN-γ, were analyzed in atherosclerotic lesions.

Main Results:

• Caspase-1 deficiency did not alter serum cholesterol levels or lipoprotein profiles.
• Caspase-1 deficiency significantly reduced atherosclerosis in the aorta by 35%-45% in both sexes and on both diets.
• Reduced expression of MHC class II and IFN-γ was observed in lesions of caspase-1 deficient mice.

Conclusions:

• Caspase-1 promotes atherosclerosis by increasing lesion inflammation.
• The mechanism involves the activation of lesion-associated immune cells and IFN-γ expression.
• Targeting caspase-1 may offer a novel therapeutic approach for atherosclerosis.