Key result
Neutrophil depletion and myeloid Wnt5a deficiency attenuate pressure overload-induced cardiac hypertrophy and preserve function.
Why the study?
Although the roles of macrophages in myocardial injury are recognized, the function of neutrophils in nonischemic cardiac pathology has received relatively little attention.
Does Wnt5a-mediated neutrophil recruitment contribute to pressure overload-induced cardiac dysfunction in mice?
Does Wnt5a-mediated neutrophil recruitment contribute to pressure overload-induced cardiac dysfunction in mice?
Wnt5a-regulated neutrophil infiltration plays a critical role in pressure overload-induced heart failure, highlighting a potential therapeutic target for nonischemic cardiac pathology.
Hypothesis-generating for myeloid Wnt5a targeting in pressure-overload HF; leaves open translation to human nonischemic cardiomyopathy.
BACKGROUND: Although the complex roles of macrophages in myocardial injury are widely appreciated, the function of neutrophils in nonischemic cardiac pathology has received relatively little attention. METHODS: To examine the regulation and function of neutrophils in pressure overload-induced cardiac hypertrophy, mice underwent treatment with Ly6G antibody to deplete neutrophils and then were subjected to transverse aortic constriction. RESULTS: Neutrophil depletion diminished transverse aortic constriction-induced hypertrophy and inflammation and preserved cardiac function. Myeloid deficiency of Wnt5a, a noncanonical Wnt, suppressed neutrophil infiltration to the hearts of transverse aortic constriction-treated mice and produced a phenotype that was similar to the neutropenic conditions. Conversely, mice overexpressing Wnt5a in myeloid cells displayed greater hypertrophic growth, inflammation, and cardiac dysfunction. Neutrophil depletion reversed the Wnt5a overexpression-induced cardiac pathology and eliminated differences in cardiac parameters between wild-type and myeloid-specific Wnt5a transgenic mice. CONCLUSIONS: These findings reveal that Wnt5a-regulated neutrophil infiltration has a critical role in pressure overload-induced heart failure.
No takes yet. Share an insight, caveat, or question.
Wang et al. (2019) studied Pressure overload-induced cardiac hypertrophy and heart failure. Neutrophil depletion (Ly6G antibody) and myeloid-specific Wnt5a knockout/overexpression vs. Isotype control antibody and wild-type mice was evaluated on Cardiac hypertrophy, cardiac function, and inflammation post-transverse aortic constriction. Neutrophil depletion and myeloid-specific Wnt5a deficiency significantly diminished pressure overload-induced cardiac hypertrophy and inflammation while preserving cardiac function in mice.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: