Immune checkpoint programmed death-1 mediates abdominal aortic aneurysm and pseudoaneurysm progression

Area of Science:

• Vascular Biology
• Immunology
• Aortic Disease Research

Background:

• Abdominal aortic aneurysms (AAAs) and pseudoaneurysms have unclear causes and pathogenesis.
• The role of programmed death-1 (PD-1) in these conditions is not fully understood.

Purpose of the Study:

• To investigate the potential of inhibiting the PD-1 pathway to decrease AAA and pseudoaneurysm formation.
• To test PD-1 inhibition in established mouse and rat models of aortic aneurysms.

Main Methods:

• Human AAA samples were analyzed for PD-1 expression.
• Mouse models used CaCl2-induced AAA, and rat models used aortic patch angioplasty.
• PD-1 inhibitors (antibody or BMS-1) were administered via intraperitoneal, intraluminal, or patch-coated methods.

Main Results:

• PD-1 and its co-expressed markers were found in human AAA tissues.
• PD-1 inhibition significantly reduced AAA progression in mouse models.
• Coating aortic patches with PD-1 inhibitors decreased pseudoaneurysm progression and inflammation in rats.

Conclusions:

• Inhibition of the PD-1 pathway shows promise as a therapeutic strategy.
• Targeting PD-1 may be effective in managing AAA and pseudoaneurysm progression.