title: Deletion of CD28 Co-stimulatory Signals Exacerbates Left Ventricular Remodeling and Increases Cardiac Rupture After Myocardial Infarction.
abstract: BACKGROUND
  Inflammatory responses, especially by CD4(+)T cells activated by dendritic cells, are known to be important in the pathophysiology of cardiac repair after myocardial infarction (MI). Although co-stimulatory signals through B7 (CD80/86) and CD28 are necessary for CD4(+)T cell activation and survival, the roles of these signals in cardiac repair after MI are still unclear.
  
  
  RESULTS
  C57BL/6 (Control) mice and CD28 knockout (CD28KO) mice were subjected to left coronary artery permanent ligation. The ratio of death by cardiac rupture within 5 days after MI was significantly higher in CD28KO mice compared with Control mice. Although there were no significant differences in the infarct size between the 2 groups, left ventricular end-diastolic and end-systolic diameters were significantly increased, and fractional shortening was significantly decreased in CD28KO mice compared with Control mice. Electron microscopic observation revealed that the extent of extracellular collagen fiber was significantly decreased in CD28KO mice compared with Control mice. The number of α-smooth muscle actin-positive myofibroblasts was significantly decreased, and matrix metalloproteinase-9 activity and the mRNA expression of interleukin-1β were significantly increased in CD28KO mice compared with Control mice.
  
  
  CONCLUSIONS
  Deletion of CD28 co-stimulatory signals exacerbates left ventricular remodeling and increases cardiac rupture after MI through prolongation of the inflammatory period and reduction of collagen fiber in the infarct scars. (Circ J 2016; 80: 1971-1979).
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kubota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tadokoro
authors.forename: Masanori
authors.initials: M
authors.lastname: Hirose
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamada-Inagawa
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takano
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000172:deficiency* / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006342:Heart Rupture, Post-Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D058628:Myofibroblasts / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction; D020257:Ventricular Remodeling
chemical_list: D018106:CD28 Antigens; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse