Hypoplastic left heart syndrome myocytes are differentiated but possess a unique phenotype
Hypoplastic left heart syndrome myocytes are differentiated but possess a unique phenotype
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DOI：
10.1016/s1054-8807(02)00127-8
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发表时间：
2003-01-01
影响因子：
3.7
通讯作者：
Perryman, MB
中科院分区：
文献类型：
--
作者：
Bohlmeyer, TJ;Helmke, S;Perryman, MB
前言：左心发育不全综合征(HLHS)是一组以左侧心脏明显发育不全为特征的先天性畸形。HLHS占生命第一年心脏死亡的近25%。虽然已经有很多关于诊断、大体形态和手术治疗的报道，但关于HLHS心肌细胞基因表达的信息尚不清楚。方法：采用常规组织学、免疫组织化学、定量聚合酶链式反应(PCR)、双向凝胶电泳法和质谱仪鉴定心肌组织。结果：HLHS患者左、右心室的组织学检查显示心肌细胞分化的特征性特征，包括横纹和间盘形成。N-钙粘素抗体免疫组织化学染色显示心肌细胞间有明显的间盘发育。然而，许多心肌细胞含有稀少的细胞质，由丰富的结缔组织和扩张的薄壁血管隔开的小而杂乱的束状排列。定量聚合酶链式反应分析表明，HLHS心脏左、右室组织均表达胎儿或“心力衰竭”基因表达模式。双向凝胶电泳法和蛋白质质谱鉴定也证实了HLHS的心肌细胞是分化的，但表达一些心脏特异蛋白的胎儿亚型。然而，所有心脏标本(n=21)的HLHS心肌细胞都异常表达血小板-内皮细胞黏附分子-1(PECAM-1，CD31)，这是细胞黏附分子(CAM)家族的成员，在组织形态发生的调节中起主要作用。这些发现表明，HLHS综合征患者的心肌细胞虽然分化，但具有独特的基因表达模式。(C)2003 Elsevier Science Inc.保留所有权利。
Introduction: Hypoplastic left heart syndrome (HLHS) is the term used to describe a group of congenital malformations characterized by marked underdevelopment of the left side of the heart. HLHS accounts for nearly 25% of cardiac deaths in the first year of life. Although much has been reported regarding diagnosis, gross morphology and surgical treatment, no information on gene expression in HLHS myocytes is available. Methods: We examined heart tissue from patients with HLHS using routine histology, inummohistochemistry, quantitative polymerase chain reaction (PCR), two-dimensional (2-D) gel electrophoresis and protein identification by mass spectrometry. Results: Histologic examination of right and left ventricles from HLHS patients revealed characteristic features of myocyte differentiation, including striations and intercalated disc formation. Immumohistochemical staining using antibody to N-cadherin demonstrated clear development of intercalated discs between myocytes. However, many of the myocytes contained scant cytoplasm and were grouped in small, disorganized bundles separated by abundant connective tissue and dilated, thin-walled vessels. Quantitative PCR analysis demonstrated that both left and right ventricular tissue from HLHS hearts expressed the fetal or "heart failure" gene expression pattern. Two-dimensional gel electrophoresis and protein identification by mass spectrometry also confirmed that myocytes from HLHS ventricles were differentiated but expressed the fetal isoform of some cardiac specific proteins. However, HLHS myocytes in all of the heart samples (n=21) were inappropriately expressing platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31), a member of the cell adhesion molecule (CAM) family that has a primary role in the regulation of tissue morphogenesis. These findings indicate that myocytes from HLHS syndrome patients, while differentiated, have a unique gene expression pattern. (C) 2003 Elsevier Science Inc. All rights reserved.