Interleukin-17A-Related Inflammation Mediates Cardiac Injury in Chronic Relapsing Psoriasis-Like Mouse Model

Area of Science:

• Immunology
• Cardiology
• Dermatology

Background:

• Psoriasis is a chronic inflammatory skin disease with recurrent relapses.
• Patients with psoriasis have an increased risk of cardiovascular comorbidities.
• The specific impact of psoriasis-related chronic inflammation on cardiac function requires further investigation.

Purpose of the Study:

• To investigate the impact of acute and chronic psoriasis-like inflammation on cardiac function in mouse models.
• To determine the role of interleukin-17A (IL-17A) in psoriasis-induced myocardial injury.
• To evaluate the therapeutic potential of IL-17A neutralisation in mitigating cardiac dysfunction.

Main Methods:

• Establishment of short-term (IMQ-ST) and long-term (IMQ-LT) psoriasis-like mouse models using imiquimod (IMQ).
• Assessment of cardiac function, myocardial tissue, and gene expression in IMQ-treated mice.
• Analysis of inflammatory markers, including IL-17A and γδT cells, in skin and heart tissues.
• Evaluation of the effects of IL-17A neutralisation on cardiac parameters in IMQ-LT mice.

Main Results:

• Both IMQ-ST and IMQ-LT models exhibited skin and cardiac inflammation characterized by increased IL-17A and IL-17A-producing γδT cells.
• Only IMQ-LT mice demonstrated impaired cardiac function, myocardial necrosis, and reduced expression of cardiac structural/functional proteins.
• IL-17A neutralisation significantly reduced myocardial injury and improved cardiac function in IMQ-LT mice.

Conclusions:

• IL-17A-mediated inflammation is present in both acute and chronic psoriasis-like conditions, affecting both skin and heart.
• Long-term, recurrent inflammation mimicking chronic psoriasis leads to myocardial injury and cardiac dysfunction.
• Targeting IL-17A offers a promising therapeutic strategy to prevent or treat cardiac complications associated with chronic psoriasis.