심부전 발생 이전 용적 과부하에 따른 인간 좌심실 심근조직의 유전자 발현 양상 = Gene Expression Profile of Volume-Overloaded Human VentricularMyocardium Prior to Developing Heart Failure

다국어 초록 (Multilingual Abstract)

Background and Objectives：Left ventricle burdened by longstanding volume-overload, undergoes variousstructural and functional alterations. Accordingly, the expressions of multiple classes of genes are likely to bealtered. However, the profile of gene expressions, specifically in a volume-overloaded left ventricle in humans,has not been explored. Subjects and Methods：The pattern of gene expression was studied, using a cDNA microarray,in myocardium from 4 normal subjects and 5 patients with chronic regurgitant valvular heart diseasewhose end-diastolic left ventricular dimension measures 65 mm or more, but whose systolic function remainedpreserved. Results：We identified 58 differentially expressed genes that were functionally classifiable in the volumeoverloadedmyocardium. Those genes involved in cell cycle/growth (up/down-regulation: 9/1), signal transduction(4/1) were mostly overexpressed in the volume-overloaded myocardium. The distributions of the geneexpressions were variable for those involved in transcription/translation (up/down-regulation: 6/7) and apoptosis(2/2). The genes related to the myocyte structure (troponin T3, tropomyosin, etc)(up/down-regulation: 1/10),as well as those related to metabolism (2/5), were underexpressed. The gene expression patterns from RT-PCRand Western blot, with randomly selected genes, were similar to those from the cDNA microarray. Conclusion：Altered expression was identified in multiple genes in the volume-overloaded human left ventricle prior to thedevelopment of heart failure. The genes related to cell growth and signal transduction were mostly overexpressed,while those related to cellular structure and metabolism appeared to be underexpressed. These results might helpin the elucidation of cellular mechanisms for the remodeling process associated with chronic volume-overloading

국문 초록 (Abstract)

배경 및 목적：장기간 용적 과부하를 받는 심근 조직은 여러 가지의 구조적, 기능적 변화가 일어난다. 이러한 심실의 재형성 과정에는 미세구조, 분자의 변화와 그에 상응하는 유전자의 발현변화가 수반된다. 본 연구는 DNA microarray의 기법을 이용하여 사람에서 용적 과부하에 의한 심실의 확장 과정에서발생하는 유전자의 발현 양상을 확인하고자 시행되었다.방 법：만성 판막 폐쇄 부전 질환으로 인하여 좌심실 수축기 내경이 65 mm 이상으로 증가한 5명의 환자와 심질환이 없는4명의 심장에서 채취한 심근 조직을 대상으로 하였으며 유전자 발현 양상은 4,600개의 cDNA가 집적된 chip을 이용하여 분석하였다.결 과：DNA microarray의 분석 결과 용적 부하 심근에서 기능적으로 분류 가능한 유전자의 변화는 57개에서 관찰되었으며 세포 주기/성장(10), 신호 전달(5), 전사/번역(13), 세포 고사(4), 세포 구조(11), 세포 대사(7), 기타 기능(7)에 관련된 유전자들 이었다. 세포 주기와 신호 전달된 유전자들은 발현 증가가 우세하였으며(세포 주기, 증가 9/감소 1; 신호 전달, 증가 4/감소 1), 전사(증가 6/감소 7)나 세포 고사(증가 2/감소 2)에서는 증감이 유사한 정도로 관찰되었다. 이에 반해서 세포 구조(증가 1/감소 10)와 세포 대사(증가 2/감소 5)에관련된 유전자들의 발현은 정상 대조군에 비해 현저하게 감소되었다. Microarray의 결과를 확인하기 위해 임의로 선택한 유전자를 대상으로 시행한 semiquantitative RT-PCR 및 western blot에서도 같은 유형을 발견할 수 있었다.결 론：이상의 결과에서 사람에서 장기간 용적 과부하에 의한 좌심실의 확장 과정에서 다양한 유전자의 발현이 변화함을 발견하였으며 세포 성장에 관한 유전자의 발현이 증가하는 반면 세포 구조와 대사에 관한 유전자는 발현이 감소하는 양상을 관찰하였다. Microarray는 향후 심질환의 병리를 이해하고 치료 방침을 구축하는데 유용한 수단이라고 생각된다.

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