Expression of Proto-oncogenes and Gene Mutation of Sarcomeric Proteins in Patients With Hypertrophic Cardiomyopathy

• Published in: Circulation research Vol. 83; no. 6; pp. 594 - 601
• Main Authors: Kai, Hisashi, Muraishi, Akihiko, Sugiu, Yuji, Nishi, Hirohumi, Seki, Yukihiko, Kuwahara, Fumitaka, Kimura, Akinori, Kato, Hirohisa, Imaizumi, Tsutomu
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 21.09.1998; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Biopsy; Cardiology. Vascular system; Cardiomyopathy, Hypertrophic - genetics; Female; Gene Expression; Genes, MHC Class II - genetics; Genes, ras - genetics; Heart; Humans; Male; Medical sciences; Middle Aged; Muscle Proteins - genetics; Mutation; Myocarditis. Cardiomyopathies; Myocardium - metabolism; Myocardium - pathology; Polymerase Chain Reaction; Proto-Oncogenes - genetics; RNA, Messenger - genetics; RNA-Directed DNA Polymerase; Sarcomeres - chemistry; Human; Myofibril; Contractile protein; Cardiovascular disease; Gene expression; Myocardial disease; Heart disease; C-Onc gene; Myosin; Hypertrophic cardiomyopathy; Myocardium; Circulatory system; Mutation; Sarcomere; Protooncogene
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.83.6.594

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 beta-MHC gene mutation has some effect on the regulation of proto-oncogene expression in HCM. (Circ Res. 1998;83:594-601.)