CD38 deficient mice are not protected from atherosclerosis.

Area of Science:

• Immunology
• Cardiovascular Biology
• Enzymology

Background:

• CD38 is a multifunctional enzyme involved in immune cell function and host defense.
• Its precise role in atherosclerosis pathogenesis remains unclear, with conflicting research findings.
• CD38 is expressed on various cell types, including immune and resident vascular cells.

Purpose of the Study:

• To investigate the impact of CD38 gene ablation on atherosclerosis development.
• To resolve discrepancies in the current literature regarding CD38's role in atherosclerosis.
• To assess atherosclerosis progression in CD38-deficient mice under hyperlipidemic conditions.

Main Methods:

• Utilized CD38 knockout (CD38-/-) and wild-type (WT) mice.
• Induced hypercholesterolemia using a PCSK9 gain-of-function mutation (D374Y) delivered via AAV vector and an atherogenic diet.
• Implanted a shear stress modifier in the carotid artery and assessed atherosclerosis at multiple sites after 9 weeks.

Main Results:

• No significant differences in atherosclerotic burden were observed between CD38-/- and WT mice in the aortic root, arch, or carotid artery.
• Monocyte infiltration and macrophage content within plaques were similar in both groups.
• Collagen deposition in atherosclerotic plaques did not differ between CD38-/- and WT mice.

Conclusions:

• CD38 deficiency does not confer protection against atherosclerosis development.
• CD38-deficient mice are not more susceptible to atherosclerosis compared to WT controls.
• These findings indicate CD38 is not a critical determinant in the pathogenesis of atherosclerosis.