Proinflammatory Protein CARD9 Is Essential for Infiltration of Monocytic Fibroblast Precursors and Cardiac Fibrosis Caused by Angiotensin Ⅱ Infusion
Background 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.Methods Twomonthold CARD9deficient (CARD9-/-) and wildtype (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.Results: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 interleukin1β (IL1 β) 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 factorβ (TGFβ) and level of myofibroblasts positive for αsmooth muscle actin (αSMA).Furthermore,Ang Ⅱ activation of nuclear factor κ B (NF κ B),JNK and p38 mitogenactivated protein kinases (MAPKs) in WT macrophages was reduced in CARD9-/-macrophages.Conclusion CARD9 plays an important role in regulating cardiac inflammation and fibrosis in response to elevated Ang Ⅱ.
Jingyuan Ren Jie Du Min Yang Guanming Qi Jiao Zheng Lixin Jia Jizhong Cheng Cui Tian Huihua Li Xin Lin
Beijing An Zhen Hospital, Capital Medical University, Beijing, China; The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute o
国内会议
北京
英文
96-97
2013-04-19（万方平台首次上网日期，不代表论文的发表时间）