Proceedings of the National Academy of Sciences of the United States of America · 2018
Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Liao Xudong, Shen Yuyan, Zhang Rongli, Sugi Keiki, Vasudevan Neelakantan T, Alaiti M Amer, Sweet David R, Zhou Lin, Qing Yulan, Gerson Stanton L, Fu Chen, Wynshaw-Boris Anthony, Hu Rui, Schwartz Martin A, Fujioka Hisashi, Richardson Brian, Cameron Mark J, Hayashi Hiroki, Stamler Jonathan S, Jain Mukesh K
Аннотация
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.