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

Ying Wang, Soichi Sano, Kosei Oshima, Miho Sano, Yosuke Watanabe, Yasufumi Katanasaka, Yoshimitsu Yura, Changhee Jung, Atsushi Anzai, Filip K. Swirski, Noyan Gokce, Kenneth Walsh

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4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)487-499
Number of pages13
JournalCirculation
Volume140
Issue number6
DOIs
Publication statusPublished - 2019 Aug 6
Externally publishedYes

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Keywords

  • heart
  • hematopoiesis
  • inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Wang, Y., Sano, S., Oshima, K., Sano, M., Watanabe, Y., Katanasaka, Y., Yura, Y., Jung, C., Anzai, A., Swirski, F. K., Gokce, N., & Walsh, K. (2019). Wnt5a-Mediated Neutrophil Recruitment Has an Obligatory Role in Pressure Overload-Induced Cardiac Dysfunction. Circulation, 140(6), 487-499. https://doi.org/10.1161/CIRCULATIONAHA.118.038820