Reduced ACTC1 expression might play a role in the onset of congenital heart disease by inducing cardiomyocyte apoptosis.
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).


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.
Department of Pediatrics, The First Affiliated Hospital of China Medical University, Shenyang, China.
Hong-Kun
HK
Jiang
Guang-Rong
GR
Qiu
Jesse
J
Li-Ling
Na
N
Xin
Kai-Lai
KL
Sun
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics; D002460:Cell Line; D002675:Child, Preschool; D002681:China; D015536:Down-Regulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C526913:ACTC1 protein, human; D000199:Actins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C505410:Casp3 protein, rat; D053148:Caspase 3