Dzimiri Nduna, Al-Bahnasi Kholod, Al-Halees Zohair
Pharmacogenomics Division, Genetics Department, King Faisal Specialist Hospital & Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
Fundam Clin Pharmacol. 2004 Feb;18(1):39-44. doi: 10.1046/j.0767-3981.2003.00212.x.
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.
目前尚不确定肥大或潜在疾病是否是心脏病进展至终末期心力衰竭时早期基因表达改变的主要触发因素。在本研究中，我们验证了这样一种观点，即在左心室超负荷疾病中，进展至心力衰竭时早期基因表达的变化与心肌肥大的表现无关。我们比较了6例扩张型心肌病（DCM）心脏和15例因二尖瓣/主动脉反流导致左心室容量超负荷（VOL）且无明显狭窄或肥厚表现的患者中早期基因c-fos、c-myc和c-jun的表达情况，以8个健康供体心脏作为对照。在VOL组中，左心室c-myc升高88%（P<0.01），右心室升高46%，左心房升高1倍（P<0.01），右心房升高54%（P<0.05）；而在DCM组中，分别升高71%（P<0.02）、55%、48%（P<0.05）和91%（P<0.05）。同样，在VOL组中，左心室c-jun升高41%（P<0.01），右心室升高39%（P<0.05），左心房升高83%（P<0.02），右心房升高21%；而在DCM组中，左心室升高13%，左心房升高29%，右心房升高41%，但右心室降低13%。相比之下，DCM组和VOL组的左心室和心房以及VOL组左心房中的c-fos略有降低，而在其他心肌腔室中保持不变。这些结果表明，在人类心肌中，这三个早期基因受到不同的调控，可能是以疾病和腔室特异性的方式，并且左心室肥大的表现并非左心室超负荷疾病中其表达升高的先决条件。
