PARP1 is required for adhesion molecule expression in atherogenesis

Area of Science:

• Cardiovascular Biology
• Inflammation Research
• Molecular Medicine

Background:

• Atherosclerosis is a leading cause of mortality, characterized by chronic inflammation.
• The precise mediators driving inflammatory cell recruitment in atherosclerosis are not fully understood.
• Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear enzyme, is implicated in acute inflammatory conditions.

Purpose of the Study:

• To investigate the role of PARP1 in the development of atherosclerosis.
• To determine if pharmacological inhibition or genetic deletion of PARP1 impacts atherosclerotic plaque formation and characteristics.

Main Methods:

• Utilized atherosclerosis-prone apolipoprotein E-deficient mice fed a high-cholesterol diet.
• Administered chronic pharmacological PARP inhibition or genetic PARP1 deletion.
• Assessed plaque formation, adhesion molecule expression, and plaque vulnerability features.

Main Results:

• Chronic PARP inhibition or PARP1 deletion decreased plaque formation by 46% and 51%, respectively.
• Reduced expression of adhesion molecules (VCAM-1, P-selectin, E-selectin) and inducible nitric oxide synthase.
• Decreased macrophage and T-cell infiltration, reduced necrotic core size, and decreased cell death, while increasing fibrous cap thickness.

Conclusions:

• Endogenous PARP1 is essential for atherogenesis in vivo.
• PARP1 inhibition mitigates atherosclerosis by reducing endothelial activation, inflammation, and plaque vulnerability.
• Targeting PARP1 represents a promising therapeutic strategy for atherosclerosis.