Myocardial hypertrophy is not a prerequisite for changes in early gene expression in left ventricular volume overload.
Currently it is not certain whether hypertrophy or the underlying disease is the primary trigger of the alterations in early gene expression in the progression of cardiac disease to end-stage heart failure. In this study, we tested the notion that in left ventricular overload disorders, the changes in early gene expression in the progression to heart failure is independent of the manifestation of cardiac hypertrophy. We compared the expression of the early genes c-fos, c-myc, and c-jun in six dilated cardiomyopathic hearts (DCM) and 15 patients with left ventricular volume overload (VOL) resulting from mitral/aortic regurgitation and no significant stenosis or hypertrophic manifestations, using eight healthy donor hearts as controls. In VOL, c-myc was elevated by 88% (P < 0.01) in the left ventricle, 46% in the right ventricle, onefold (P < 0.01) in the left atrium, and 54% (P < 0.05) in the right atrium, while in DCM, it was increased by 71% (P < 0.02), 55%, 48% (P < 0.05) and 91% (P < 0.05), respectively. Similarly, c-jun was elevated by 41% (P < 0.01) in the left ventricle, 39% (P < 0.05) in the right ventricle, 83% (P < 0.02) in the left atrium and 21% in the right atrium in VOL, while in DCM it was elevated by 13% in the left ventricle, 29% in the left atrium, and 41% in the right atrium, but decreased by 13% in the right ventricle. In contrast, c-fos was slightly decreased in the left ventricle and atrium of both DCM and VOL, and in left atrium of the VOL group, but remained unchanged in the other myocardial chambers. These results show that, in the human myocardium, the three early genes are regulated differently, possibly in disease- and chamber-specific fashions, and manifestation of left ventricular hypertrophy is not a prerequisite for the elevation in their expression in left ventricular overload disorders.
Dzimiri
Nduna
N
Pharmacogenomics Division, Genetics Department, King Faisal Specialist Hospital & Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. dzimiri@kfshrc.edu.sa
Al-Bahnasi
Kholod
K
Al-Halees
Zohair
Z
D000328:Adult; D001022:Aortic Valve Insufficiency / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics* / Q000473:pathology*; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000235:genetics*; D016762:Genes, fos / Q000235:genetics / Q000502:physiology; D016758:Genes, jun / Q000235:genetics / Q000502:physiology; D016259:Genes, myc / Q000235:genetics / Q000502:physiology; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D008944:Mitral Valve Insufficiency / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018487:Ventricular Dysfunction, Left / Q000235:genetics* / Q000473:pathology*; D016277:Ventricular Function, Left / Q000502:physiology
D017931:DNA Primers; D012333:RNA, Messenger