title: Proinflammatory protein CARD9 is essential for infiltration of monocytic fibroblast precursors and cardiac fibrosis caused by Angiotensin II infusion.
abstract: 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
  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.
  
  
  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 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.
  
  
  CONCLUSIONS
  CARD9 plays an important role in regulating cardiac inflammation and fibrosis in response to elevated Ang II.
authors: Beijing Anzhen Hospital Affiliated to the Capital Medical University, Beijing, China.
authors: Jingyuan
authors: J
authors: Ren
authors: Min
authors: M
authors: Yang
authors: Guanming
authors: G
authors: Qi
authors: Jiao
authors: J
authors: Zheng
authors: Lixin
authors: L
authors: Jia
authors: Jizhong
authors: J
authors: Cheng
authors: Cui
authors: C
authors: Tian
authors: Huihua
authors: H
authors: Li
authors: Xin
authors: X
authors: Lin
authors: Jie
authors: J
authors: Du
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects; D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000172:deficiency / Q000502:physiology*; D005355:Fibrosis; D007249:Inflammation / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology*; D058628:Myofibroblasts / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D053468:CARD Signaling Adaptor Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D000804:Angiotensin II