Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy

Xudong Liao, Yuyan Shen, Rongli Zhang, Keiki Sugi, Neelakantan T. Vasudevan, M. Amer Alaiti, David R. Sweet, Lin Zhou, Yulan Qing, Stanton L. Gerson, Chen Fu, Anthony Wynshaw-Boris, Rui Hu, Martin A. Schwartz, Hisashi Fujioka, Brian Richardson, Mark J. Cameron, Hiroki Hayashi, Jonathan S. Stamler, Mukesh K. Jain

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


Nonischemic cardiomyopathy (NICM) resulting from long-standing hypertension, valvular disease, and genetic mutations is a major cause of heart failure worldwide. Recent observations suggest that myeloid cells can impact cardiac function, but the role of tissue-intrinsic vs. tissue-extrinsic myeloid cells in NICM remains poorly understood. Here, we show that cardiac resident macrophage proliferation occurs within the first week following pressure overload hypertrophy (POH; a model of heart failure) and is requisite for the heart’s adaptive response. Mechanistically, we identify Kruppel-like factor 4 (KLF4) as a key transcription factor that regulates cardiac resident macrophage proliferation and angiogenic activities. Finally, we show that blood-borne macrophages recruited in late-phase POH are detrimental, and that blockade of their infiltration improves myocardial angiogenesis and preserves cardiac function. These observations demonstrate previously unappreciated temporal and spatial roles for resident and nonresident macrophages in the development of heart failure.

Original languageEnglish (US)
Pages (from-to)E4661-E4669
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
StatePublished - May 15 2018
Externally publishedYes


  • Angiogenesis
  • Cardiac macrophage
  • Pressure overload hypertrophy

ASJC Scopus subject areas

  • General


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