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

Research output: Contribution to journalArticle

1 Citation (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

Fingerprint

Neutrophil Infiltration
Neutrophils
Pressure
Constriction
Pathology
Inflammation
Cardiomegaly
Myeloid Cells
Hypertrophy
Transgenic Mice
Heart Failure
Macrophages
Phenotype
Antibodies
Wounds and Injuries
Growth

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., ... 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

Wnt5a-Mediated Neutrophil Recruitment Has an Obligatory Role in Pressure Overload-Induced Cardiac Dysfunction. / Wang, Ying; Sano, Soichi; Oshima, Kosei; Sano, Miho; Watanabe, Yosuke; Katanasaka, Yasufumi; Yura, Yoshimitsu; Jung, Changhee; Anzai, Atsushi; Swirski, Filip K.; Gokce, Noyan; Walsh, Kenneth.

In: Circulation, Vol. 140, No. 6, 06.08.2019, p. 487-499.

Research output: Contribution to journalArticle

Wang, Y, Sano, S, Oshima, K, Sano, M, Watanabe, Y, Katanasaka, Y, Yura, Y, Jung, C, Anzai, A, Swirski, FK, Gokce, N & Walsh, K 2019, 'Wnt5a-Mediated Neutrophil Recruitment Has an Obligatory Role in Pressure Overload-Induced Cardiac Dysfunction', Circulation, vol. 140, no. 6, pp. 487-499. https://doi.org/10.1161/CIRCULATIONAHA.118.038820
Wang, Ying ; Sano, Soichi ; Oshima, Kosei ; Sano, Miho ; Watanabe, Yosuke ; Katanasaka, Yasufumi ; Yura, Yoshimitsu ; Jung, Changhee ; Anzai, Atsushi ; Swirski, Filip K. ; Gokce, Noyan ; Walsh, Kenneth. / Wnt5a-Mediated Neutrophil Recruitment Has an Obligatory Role in Pressure Overload-Induced Cardiac Dysfunction. In: Circulation. 2019 ; Vol. 140, No. 6. pp. 487-499.
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