title: Expression of proto-oncogenes and gene mutation of sarcomeric proteins in patients with hypertrophic cardiomyopathy.
abstract: Several mutations of cardiac beta-myosin heavy chain (beta-MHC) gene were reported in patients with hypertrophic cardiomyopathy (HCM). Involvement of proto-oncogenes has been shown in the mechanism of experimental cardiac hypertrophy. This study sought to examine the effects of c-H-ras and c-myc expression in the steady-state myocardium on hypertrophic changes and to evaluate the possible interaction between beta-MHC mutation and proto-oncogene expression in HCM. Endomyocardial biopsy was performed in 17 HCM patients (5 beta-MHC mutations and 1 troponin T mutation) and 7 control subjects (no mutation). Reverse transcription-polymerase chain reaction analysis revealed c-H-ras expression in all members of both groups. Cardiomyocyte size was correlated with the expression level of c-H-ras (P<0.001), and c-H-ras expression was upregulated in HCM patients (P<0.01). HCM patients with a beta-MHC mutation had the higher c-H-ras expression than did control subjects or patients without a mutation (P<0.01). c-myc mRNA was expressed in 7 of 17 HCM patients but not in control subjects. Myocyte size was greater in c-myc-positive HCM patients than in control subjects and c-myc-negative HCM patients (P<0.001 and P<0.05, respectively). The proto-oncogene expression did not affect clinical findings, myocardial fibrosis, or disarray. In conclusion, c-H-ras and c-myc expression in the steady-state myocardium may play a role in the hypertrophic mechanism in HCM. It is possible that ss-MHC gene mutation has some effect on the regulation of proto-oncogene expression in HCM.
authors.affiliation: From the Cardiovascular Research Institute, Kurume University and the Third Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. kaihm@kurume.ktarn.or.jp
authors.forename: H
authors.initials: H
authors.lastname: Kai
authors.forename: A
authors.initials: A
authors.lastname: Muraishi
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiu
authors.forename: H
authors.initials: H
authors.lastname: Nishi
authors.forename: Y
authors.initials: Y
authors.lastname: Seki
authors.forename: F
authors.initials: F
authors.lastname: Kuwahara
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005802:Genes, MHC Class II / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012194:RNA-Directed DNA Polymerase; D012518:Sarcomeres / Q000737:chemistry
chemical_list: C000715470:MAS1 protein, human; D009124:Muscle Proteins; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase