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

Circ J. 2010 Nov;74(11):2410-8. doi: 10.1253/circj.cj-10-0234. Epub 2010 Oct 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Age Factors
  • Animals
  • Apoptosis*
  • Blotting, Western
  • Case-Control Studies
  • Caspase 3 / genetics
  • Cell Line
  • Child, Preschool
  • China
  • 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
  • RNA Interference
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection


  • ACTC1 protein, human
  • Actins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Casp3 protein, rat
  • Caspase 3