title: Deficiency of IL-12p35 improves cardiac repair after myocardial infarction by promoting angiogenesis.
abstract: OBJECTIVE
  IL-12p35 is a pro-inflammatory cytokine that participates in a variety of inflammatory diseases. This study aimed to determine whether IL-12 regulates cardiac injury and repair following acute myocardial infarction (AMI) and investigate the underlying mechanisms.
  
  
  RESULTS
  Mice with AMI showed a marked increase in IL-12p35 expression of ischaemic cardiac tissues. IL-12 was mainly produced by CD11b(+) monocytes. Cardiac functions were significantly improved in IL-12p35 knockout (p35-KO) mice compared with wild-type (WT) littermates in response to AMI. IL-12p35 deficiency attenuated the infarct scar and hypertrophy compared with WT mice. RNA transcriptome sequencing and quantitative RT-PCR analysis of CD11b(+) monocytes isolated from WT and p35-KO ischaemic hearts revealed a distinct transcriptional profile in p35-KO CD11b(+) monocytes, displaying pro-angiogenesis and anti-inflammation properties. Angiogenesis was enhanced in p35-KO mice with AMI and hindlimb ischaemia. Moreover, tube formation assay and Matrigel plug analysis demonstrated that IL-12 inhibition of angiogenesis was dependent on monocytes. IL-12p35 deficiency inhibited inflammation by reducing chemokine production and monocyte infiltration into the heart. Finally, administration of an IL-12p35-neutralizing antibody limited AMI-induced inflammatory cell infiltration into the heart and improved angiogenesis and cardiac function.
  
  
  CONCLUSIONS
  Deficiency of IL-12p35 limited AMI-induced cardiac injury by promoting pro-angiogenesis and anti-inflammatory functions of monocytes.
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Kan
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Youcai
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China jdu@bcm.edu lyllyl_1111@163.com.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovative Research Center for Cardiovascular Diseases, Beijing 100029, China jdu@bcm.edu lyllyl_1111@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism*; D053765:Interleukin-12 Subunit p35 / Q000172:deficiency / Q000378:metabolism*; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*
chemical_list: D053765:Interleukin-12 Subunit p35
keywords: Angiogenesis; IL-12; Monocyte; Myocardial infarction