Wnt5a-Mediated Neutrophil Recruitment Has an Obligatory Role in Pressure Overload-Induced Cardiac Dysfunction

Area of Science:

• Cardiology
• Immunology
• Molecular Biology

Background:

• Macrophages' roles in myocardial injury are known, but neutrophils in nonischemic cardiac pathology are understudied.
• Investigating neutrophil function in pressure overload-induced cardiac hypertrophy is crucial for understanding heart failure.

Purpose of the Study:

• To elucidate the role and regulation of neutrophils in pressure overload-induced cardiac hypertrophy.
• To determine the involvement of Wnt5a signaling in neutrophil infiltration and cardiac pathology.

Main Methods:

• Mice were treated with Ly6G antibody to deplete neutrophils.
• Mice underwent transverse aortic constriction (TAC) to induce pressure overload.
• Wnt5a expression was manipulated in myeloid cells (deficiency or overexpression).

Main Results:

• Neutrophil depletion attenuated TAC-induced cardiac hypertrophy, inflammation, and preserved cardiac function.
• Myeloid Wnt5a deficiency suppressed neutrophil infiltration and mimicked neutropenic effects.
• Wnt5a overexpression in myeloid cells exacerbated cardiac hypertrophy, inflammation, and dysfunction.

Conclusions:

• Wnt5a-regulated neutrophil infiltration is critical in pressure overload-induced heart failure.
• Targeting neutrophil infiltration may offer therapeutic strategies for cardiac hypertrophy and heart failure.