title: Inflammatory response to acute myocardial infarction augments neointimal hyperplasia after vascular injury in a remote artery.
abstract: OBJECTIVE
  Percutaneous coronary intervention (PCI) is currently the most widely accepted treatment for acute myocardial infarction (AMI). It remains unclear, however, whether post-AMI conditions might exacerbate neointimal hyperplasia and restenosis following PCI. Given that both a medial smooth muscle cell lineage and a bone marrow (BM)-derived hematopoietic stem cell lineage are now thought to contribute to neointima formation, the primary aims of the present study were to determine whether AMI augments neointimal hyperplasia at sites of arterial injury, and whether BM-derived cells contribute to that process.
  
  
  RESULTS
  We simultaneously generated models of AMI and arterial injury in the same mice, some of which had received BM transplantation. We found that AMI augments neointimal hyperplasia at sites of femoral artery injury by approximately 35% (P<0.05), but that while BM-derived cells contributed to neointimal hyperplasia, they did not contribute to the AMI-related augmentation. Expression of interleukin (IL)-6 mRNA was approximately 7-fold higher in the neointimas of mice subjected to both AMI and arterial injury than in those of mice subjected to arterial injury alone. In addition, we observed increased synthesis of tumor necrosis factor (TNF)-alpha within infarcted hearts and TNF-alpha receptor type 1 (TNFR1) within injured arteries. Chronic treatment with pentoxifylline, which mainly inhibits TNF-alpha synthesis, reduced levels of circulating TNF-alpha and attenuated neointimal hyperplasia after AMI.
  
  
  CONCLUSIONS
  Conditions after AMI could exacerbate postangioplasty restenosis, not by increasing mobilization of BM-derived cells, but by stimulating signaling via TNF-alpha, TNFR1 and IL-6.
authors.affiliation: First Department of Internal Medicine, Nara Medical University, 84 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Takaoka
authors.forename: Shiro
authors.initials: S
authors.lastname: Uemura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawata
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Imagawa
authors.forename: Yukiji
authors.initials: Y
authors.lastname: Takeda
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Nakatani
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Naya
authors.forename: Manabu
authors.initials: M
authors.lastname: Horii
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Yoshimasa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005263:Femoral Artery / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D017539:Tunica Intima / Q000473:pathology; D014657:Vasculitis / Q000209:etiology* / Q000473:pathology*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D037342:Pertussis Toxin