Proinflammatory protein CARD9 is essential for infiltration of monocytic fibroblast precursors and cardiac fibrosis caused by Angiotensin II infusion.
Proinflammatory protein CARD9 is essential for infiltration of monocytic fibroblast precursors and cardiac fibrosis caused by Angiotensin II infusion.
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DOI：
10.1038/ajh.2011.42
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发表时间：
2011-06
影响因子：
3.2
通讯作者：
Du, Jie
中科院分区：
文献类型：
--
作者：
Ren, Jingyuan;Yang, Min;Qi, Guanming;Zheng, Jiao;Jia, Lixin;Cheng, Jizhong;Tian, Cui;Li, Huihua;Lin, Xin;Du, Jie
血管紧张素II（Ang II）诱导的心脏重塑与炎症和纤维化的潜在机制已被充分证明。胞质衔接子胱天蛋白酶募集结构域9（CARD 9）已经涉及先天性免疫应答。我们的目的是研究CARD 9在血管紧张素II诱导的炎症和心脏纤维化中的作用。将两个月大的CARD 9缺陷型（CARD 9-/-）和野生型（WT）雄性小鼠输注Ang II（1，500 ng/kg/min）或生理盐水7天。心脏切片用苏木精和伊红以及Masson三色染色，并通过免疫组织化学进行检查;并在从小鼠获得的巨噬细胞中测量活性和蛋白质水平。输注Ang II的WT小鼠显示心脏中CARD 9+巨噬细胞显著增加，但CARD 9 −/−小鼠显示巨噬细胞浸润和促炎细胞因子（包括白细胞介素-1 β（IL-1β）和结缔组织生长因子（CTGF））表达显著抑制。重要的是，在CARD 9 −/−心脏中，Ang II诱导的心脏纤维化（细胞外基质和胶原I沉积）减少，转化生长因子-β（TGF-β）的表达和α-平滑肌肌动蛋白（α-SMA）阳性的肌成纤维细胞水平也减少。此外，在CARD 9 −/−巨噬细胞中，WT巨噬细胞中的核因子-κB（NF-κB）、JNK和p38丝裂原活化蛋白激酶（MAPK）的Ang II活化减少。CARD 9在调节心脏炎症和纤维化中起重要作用，以响应升高的Ang II。
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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影响因子：
8.3
作者：
Huang, Xiao R.;Chung, Arthur C. K.;Lan, Hui Y.
通讯作者：
Lan, Hui Y.
DOI：
10.1073/pnas.0601947103
发表时间：
2007-01-02
影响因子：
11.1
作者：
McAllister-Lucas, Linda M.;Ruland, Juergen;Lucas, Peter C.
通讯作者：
Lucas, Peter C.
影响因子：
4.8
作者：
Bertin, J;Guo, Y;Alnemri, ES
通讯作者：
Alnemri, ES
影响因子：
--
作者：
Bruckner, AL
通讯作者：
Bruckner, AL
影响因子：
4.8
作者：
Ma, YW;Zhang, LP;Du, J
通讯作者：
Du, J