Reduced ACTC1 Expression Might Play a Role in the Onset of Congenital Heart Disease by Inducing Cardiomyocyte Apoptosis

• Published in: Circulation Journal Vol. 74; no. 11; pp. 2410 - 2418
• Main Authors: Jiang, Hong-Kun, Qiu, Guang-Rong, Li-Ling, Jesse, Xin, Na, Sun, Kai-Lai
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 2010
• Subjects: Actins - genetics; Actins - metabolism; Age Factors; Animals; Apoptosis; Bcl-2; Blotting, Western; Cardiac α actin 1; Case-Control Studies; Caspase 3 - genetics; Caspase-3; Cell Line; Child, Preschool; China; Congenital heart disease; Down-Regulation; Female; Gene Expression Regulation, Developmental; Gestational Age; Heart Defects, Congenital - genetics; Heart Defects, Congenital - metabolism; Heart Defects, Congenital - pathology; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Infant; Infant, Newborn; Male; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Proto-Oncogene Proteins c-bcl-2 - genetics; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Messenger - metabolism; Transfection; China
• ISSN: 1346-9843; 1347-4820; 1347-4820
• DOI: 10.1253/circj.CJ-10-0234

Background: The Cardiac α actin 1 gene (ACTC1) has been related to familial atrial septal defects. This study was set to explore a potential role of this gene in the formation of sporadic congenital heart disease (CHD). Methods and Results: Assessment of cardiac tissue samples from 33 patients with sporadic CHD (gestational age (GA) 18 weeks-49 months) with real-time RT-PCR, Western blotting and immunohistochemistry has revealed a markedly decreased ACTC1 expression in the majority of samples (78.8%) compared with autopsied normal heart tissue from aged-matched subjects (GA 17 weeks-36 months). Also, as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, the proportion of apoptotic cardiomyocytes in samples featuring down-regulated ACTC1 expression (Group 1) was significantly greater than those with normal expression (Group 2) and the controls (P<0.01). The proportion of apoptotic cells strongly correlated with the expression of ACTC1 (r=-0.918, P<0.01). A study of 2 essential genes involved in apoptosis, Caspase-3 and Bcl-2, confirmed that the former has significantly increased expression, whilst the latter has decreased expression in Group 1 than in the other groups (P<0.01). Transfection of a small interfering RNA targeting, Actc1 (Actc1-siRNA), to a cardiomyocyte cell line, H9C2, also detected more apoptotic cells. Conclusions: Reduced ACTC1 expression might play a role in the onset of CHD through induction of cardiomyocyte apoptosis. (Circ J 2010; 74: 2410-2418)