Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects against stress-induced cardiomyopathy

J Pathol. 2015 Dec;237(4):482-94. doi: 10.1002/path.4594. Epub 2015 Sep 1.


The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the ACP1 gene, is a ubiquitously expressed phosphatase whose in vivo function in the heart and in cardiac diseases remains unknown. To investigate the in vivo role of LMPTP in cardiac function, we generated mice with genetic inactivation of the Acp1 locus and studied their response to long-term pressure overload. Acp1(-/-) mice develop normally and ageing mice do not show pathology in major tissues under basal conditions. However, Acp1(-/-) mice are strikingly resistant to pressure overload hypertrophy and heart failure. Lmptp expression is high in the embryonic mouse heart, decreased in the postnatal stage, and increased in the adult mouse failing heart. We also show that LMPTP expression increases in end-stage heart failure in humans. Consistent with their protected phenotype, Acp1(-/-) mice subjected to pressure overload hypertrophy have attenuated fibrosis and decreased expression of fibrotic genes. Transcriptional profiling and analysis of molecular signalling show that the resistance of Acp1(-/-) mice to pathological cardiac stress correlates with marginal re-expression of fetal cardiac genes, increased insulin receptor beta phosphorylation, as well as PKA and ephrin receptor expression, and inactivation of the CaMKIIδ pathway. Our data show that ablation of Lmptp inhibits pathological cardiac remodelling and suggest that inhibition of LMPTP may be of therapeutic relevance for the treatment of human heart failure.

Keywords: ACP1; cardiac hypertrophy; heart failure; low molecular weight protein tyrosine phosphatase; protein tyrosine phosphatase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Heart Failure / metabolism*
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Protein Tyrosine Phosphatases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Takotsubo Cardiomyopathy / metabolism*


  • Proto-Oncogene Proteins
  • ACP1 protein, human
  • Acp1 protein, mouse
  • Protein Tyrosine Phosphatases