Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Liao, X; Shen, Y; Zhang, R; Sugi, K; Vasudevan, NT; Alaiti, MA; Sweet, DR; Zhou, L; Qing, Y; Gerson, SL; Fu, C; Wynshaw-Boris, A; Hu, R; Schwartz, MA; Fujioka, H; Richardson, B; Cameron, MJ; Hayashi, H; Stamler, JS; Jain, MK

Published Date

  • May 2018

Published In

Volume / Issue

  • 115 / 20

Start / End Page

  • E4661 - E4669

PubMed ID

  • 29712858

Pubmed Central ID

  • 29712858

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1720065115

Language

  • eng