title: CARD9 mediates necrotic smooth muscle cell-induced inflammation in macrophages contributing to neointima formation of vein grafts.
abstract: OBJECTIVE
  Inflammation plays an important role in the neointima formation of grafted veins. However, the initiation of inflammation in grafted veins is still unclear. Here, we investigated the role and underlying mechanism of an innate immunity signalling protein, caspase-associated recruitment domain 9 (CARD9) in vein grafts in mice.
  
  
  RESULTS
  In early murine vein grafts, we observed robust death of smooth muscle cells (SMCs), which was accompanied by infiltration of macrophages and expression of pro-inflammatory cytokines. Meanwhile, SMC necrosis was associated with the expression of pro-inflammatory cytokines in macrophages in vitro. To explore the mediators of necrotic SMC-induced inflammation in grafted veins from mice, we examined the expression of CARD family proteins and found CARD9 highly expressed in infiltrated macrophages of grafted veins. CARD9-knockout (KO) inhibited necrotic SMC-induced pro-inflammatory cytokine expression and NF-κB activation. Furthermore, CARD9-KO suppressed necrotic SMC-induced expression of VEGF in macrophages. Finally, CARD9-KO decreased neointima formation of grafted veins in mice.
  
  
  CONCLUSIONS
  The innate immune protein CARD9 in macrophages may mediate necrotic SMC-induced inflammation by activating NF-κB and contributed to neointima formation in the vein grafts.
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Shi
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Jia
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China jdu@bcm.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000473:pathology* / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D009336:Necrosis; D058426:Neointima / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D014680:Veins / Q000637:transplantation*
chemical_list: D053468:CARD Signaling Adaptor Proteins; C513280:Card9 protein, mouse; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger
keywords: CARD9; Cardiovascular inflammation; Macrophage; Neointima; Vein graft