title: Nonmuscle and smooth muscle myosin heavy chain expression in rejected cardiac allografts. A study in rat and monkey models.
abstract: BACKGROUND
  Diagnosis of acute rejection and graft arteriosclerosis (chronic rejection) is critical to the success of cardiac transplantation, but accurate diagnosis is often difficult. We have reported that there are three types of vascular myosin heavy chain (MHC) isoforms: SM1, SM2, and SMemb. SM2 is specifically expressed in differentiated smooth muscle cells (SMCs). SMemb is a nonmuscle-type MHC abundantly expressed in SMCs of fetal aorta.
  
  
  RESULTS
  To evaluate the usefulness of MHC expression for diagnosis and analysis of acute and chronic rejection, heterotopic cardiac transplantation was performed in rats and monkeys. Immunohistochemistry, electron microscopy, and Northern blot assay were performed to evaluate MHC expression. SMemb was expressed in spindle-shaped cells located in acutely rejected myocardium in the rats and monkeys. These cells were also observed in areas lacking cellular infiltration. These SMemb-positive cells were activated fibroblasts or myofibroblasts. SMemb mRNA was enhanced parallel to the progression of acute rejection. In the coronary arteries of chronically rejected allografts, enhanced SMemb and reduced SM2 expression was observed in both thickened intima and media. The reduced medial SM2 expression was observed before the intimal thickening occurred. These cells were phenotypically modulated SMCs.
  
  
  CONCLUSIONS
  Altered expression of MHC isoforms is a sensitive indicator in the diagnosis of acute and chronic cardiac rejection. The pathophysiology of this alteration in MHC isoform expression should be studied further to elucidate the pathogenesis of cardiac rejection.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Isobe
authors.forename: M
authors.initials: M
authors.lastname: Aikawa
authors.forename: M
authors.initials: M
authors.lastname: Kawauchi
authors.forename: I
authors.initials: I
authors.lastname: Shiojima
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: A
authors.initials: A
authors.lastname: Tojo
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Nishikawa
authors.forename: T
authors.initials: T
authors.lastname: Sakai
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: R
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000473:pathology; D006084:Graft Rejection; D016027:Heart Transplantation; D007150:Immunohistochemistry; D008251:Macaca; D008297:Male; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000737:chemistry*; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology; D018994:Myosin Light Chains / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
chemical_list: D018994:Myosin Light Chains; D012333:RNA, Messenger