Abstract 15317: Deletion of Low Molecular Weight Protein Tyrosine Phosphatase (Acp1) Protects Against Stress-induced Cardiomyopathy
Background: The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the ACP1 gene, is a ubiquitously expressed phosphatase whose in vivo function remains poorly understood. Genetic studies revealed an association between ACP1 and a variety of human cardiovascular disorders. However, evidence of a direct involvement of LMPTP in cardiac diseases is still lacking.
Methodology: We generated the first mouse model of Lmptp deficiency and studied the response of the mice under basal condition or to long-term pressure overload using comprehensive experimental approaches such as q-PCR, siRNA technology, fluorescent microscopy and immuneprecipitation technique.
Results: Acp1 -/- mice develop normally, and aging mice do not show any obvious signs of pathology in major tissues under basal condition. 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 post-natal stage, and increased in the adult mouse and human failing heart. Consistent with their protected phenotype, Acp1 -/- mice subjected to pressure overload hypertrophy have attenuated fibrosis and decreased expression of hypertrophic markers. Transcriptional profiling and analysis of molecular signaling shows that the resistance of Acp1 -/- mice to pathological cardiac stress correlates with marginal expression of fetal cardiac genes, increased insulin receptor beta phosphorylation and inactivation of CaMKIIδ pathway.
Conclusion: Our data show that ablation of Lmptp inhibits pathological cardiac remodeling and suggest that inhibition of LMPTP may be of therapeutic relevance for the treatment of heart failure in human.
Author Disclosures: S. Mahmoud: None. F.A. Wade: None. P. Quijada: None. K.A. Mohamed Adib Al-Haffar: None. M.A. Kunhi: None. H. Toko: None. Q. Marashly: None. K. Belhaj: None. E. Ibrahim: None. S.M. Stanford: None. R. Alvarez: None. Y. Liu: None. D. Colak: None. M.C. Jordan: None. K.P. Roos: None. W.A. Al-Habeeb: None. M. Sussman: None. N. Bottini: None. C. Poizat: None.
- © 2015 by American Heart Association, Inc.