Bohlmeyer Teresa J, Helmke Steve, Ge Shuping, Lynch Jennifer, Brodsky Gary, Sederberg James H, Robertson Alastair D, Minobe Wayne, Bristow Michael R, Perryman M Benjamin
Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver, CO 80246, USA.
Cardiovasc Pathol. 2003 Jan-Feb;12(1):23-31. doi: 10.1016/s1054-8807(02)00127-8.
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.
We examined heart tissue from patients with HLHS using routine histology, immunohistochemistry, quantitative polymerase chain reaction (PCR), two-dimensional (2-D) gel electrophoresis and protein identification by mass spectrometry.
Histologic examination of right and left ventricles from HLHS patients revealed characteristic features of myocyte differentiation, including striations and intercalated disc formation. Immunohistochemical 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.
左心发育不全综合征（HLHS）是用于描述一组以心脏左侧显著发育不全为特征的先天性畸形的术语。HLHS占一岁以内心脏死亡病例的近25%。尽管关于诊断、大体形态学和外科治疗已有大量报道，但尚无关于HLHS心肌细胞基因表达的信息。
我们使用常规组织学、免疫组织化学、定量聚合酶链反应（PCR）、二维（2-D）凝胶电泳和质谱蛋白质鉴定技术，对HLHS患者的心脏组织进行了检查。
HLHS患者左右心室的组织学检查显示出心肌细胞分化的特征性表现，包括横纹和闰盘形成。使用抗N-钙黏蛋白抗体进行免疫组织化学染色，显示心肌细胞之间闰盘清晰发育。然而，许多心肌细胞胞质稀少，成小而无序的束状排列，束间有丰富的结缔组织和扩张的薄壁血管分隔。定量PCR分析表明，HLHS心脏的左右心室组织均表达胎儿期或“心力衰竭”基因表达模式。二维凝胶电泳和质谱蛋白质鉴定也证实，HLHS心室的心肌细胞已分化，但表达一些心脏特异性蛋白质的胎儿异构体。然而，所有心脏样本（n = 21）中的HLHS心肌细胞均异常表达血小板内皮细胞黏附分子-1（PECAM-1，CD31），它是细胞黏附分子（CAM）家族的成员，在组织形态发生调控中起主要作用。这些发现表明，HLHS综合征患者的心肌细胞虽已分化，但具有独特的基因表达模式。
