Proinflammatory Protein CARD9 Is Essential for Infiltration of Monocytic Fibroblast Precursors and Cardiac Fibrosis Caused by Angiotensin II Infusion
In: American Journal of Hypertension, Jg. 24 (2011-06-01), S. 701-707
Online
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Zugriff:
Angiotensin II (Ang II)-induced cardiac remodeling with the underlying mechanisms involving inflammation and fibrosis has been well documented. Cytosolic adaptor caspase recruitment domain 9 (CARD9) has been implicated in the innate immune response. We aimed to examine the role of CARD9 in inflammation and cardiac fibrosis induced by Ang II.Two-month-old CARD9-deficient (CARD9(-/-)) and wild-type (WT) male mice were infused with Ang II (1,500 ng/kg/min) or saline for 7 days. Heart sections were stained with hematoxylin and eosin and Masson trichrome and examined by immunohistochemistry; and activity and protein levels were measured in macrophages obtained from mice.WT mice with Ang II infusion showed a marked increase in CARD9(+) macrophages in the heart, but CARD9(-/-) mice showed significantly suppressed macrophage infiltration and expression of proinflammatory cytokines, including interleukin-1β (IL-1β) and connective tissue growth factor (CTGF). Importantly, Ang II-induced cardiac fibrosis (extracellular matrix and collagen I deposition) was diminished in CARD9(-/-) hearts, as was the expression of transforming growth factor-β (TGF-β) and level of myofibroblasts positive for α-smooth muscle actin (α-SMA). Furthermore, Ang II activation of nuclear factor-κB (NF-κB), JNK and p38 mitogen-activated protein kinases (MAPKs) in WT macrophages was reduced in CARD9(-/-) macrophages.CARD9 plays an important role in regulating cardiac inflammation and fibrosis in response to elevated Ang II.
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Proinflammatory Protein CARD9 Is Essential for Infiltration of Monocytic Fibroblast Precursors and Cardiac Fibrosis Caused by Angiotensin II Infusion
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Autor/in / Beteiligte Person: | Ren, Jingyuan ; Yang, Min ; Cheng, Jizhong ; Zheng, Jiao ; Jia, Lixin ; Li, Hui-Hua ; Lin, Xin ; Du, Jie ; Tian, Cui ; Qi, Guanming |
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Zeitschrift: | American Journal of Hypertension, Jg. 24 (2011-06-01), S. 701-707 |
Veröffentlichung: | Oxford University Press (OUP), 2011 |
Medientyp: | unknown |
ISSN: | 1941-7225 (print) ; 0895-7061 (print) |
DOI: | 10.1038/ajh.2011.42 |
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