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RNA interference targeting SHP-1 attenuates myocardial infarction in rats.
Sugano, Masahiro; Tsuchida, Keiko; Hata, Tomoji; Makino, Naoki.
Affiliation
  • Sugano M; Department of Molecular and Cellular Biology, Division of Molecular and Clinical Gerontology, Medical Institute of Bioregulation, Kyushu University, Beppu, Oita, Japan.
FASEB J ; 19(14): 2054-6, 2005 Dec.
Article in En | MEDLINE | ID: mdl-16223786
The Src homology domain 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1) plays a key role in apoptosis and decreases phosphorylation of Akt. Apoptosis of cardiomyocytes is thought to contribute to the increased area of acute myocardial infarction (AMI), and Akt activation exerts a powerful cardioprotective effect after ischemia. Thus, a therapeutic strategy designed to inhibit expression of SHP-1 would be beneficial in AMI. Here we report that siRNA targeting SHP-1 reduced infarct size in a rat model of AMI. Upon injection into the ischemic left ventricular wall, the vector-based siRNA significantly suppressed the increase in the SHP-1 mRNA and the SHP-1 protein levels. The siRNA vector also significantly reduced the SHP-1 that bound to Fas-R. The SHP-1 siRNA vector increased phospho-Akt and reduced DNA fragmentation and caspase activity compared with the scramble siRNA vector. Finally, the area of myocardial infarction was significantly smaller with the SHP-1 siRNA vector than with the scramble siRNA vector at 2 days after LCA ligation. In conclusion, SHP-1 in the heart increased from the early stage of AMI, and this increase was thought to contribute to the increased area of myocardial infarction. Suppression of SHP-1 with the SHP-1 siRNA vector markedly reduced the infarct size in AMI.
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Collection: 01-internacional Database: MEDLINE Main subject: Protein Tyrosine Phosphatases / Myocytes, Cardiac / RNA Interference / Intracellular Signaling Peptides and Proteins / Myocardial Infarction / Myocardium Type of study: Prognostic_studies Limits: Animals Language: En Journal: FASEB J Journal subject: BIOLOGIA / FISIOLOGIA Year: 2005 Document type: Article Affiliation country: Japan Country of publication: United States
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Collection: 01-internacional Database: MEDLINE Main subject: Protein Tyrosine Phosphatases / Myocytes, Cardiac / RNA Interference / Intracellular Signaling Peptides and Proteins / Myocardial Infarction / Myocardium Type of study: Prognostic_studies Limits: Animals Language: En Journal: FASEB J Journal subject: BIOLOGIA / FISIOLOGIA Year: 2005 Document type: Article Affiliation country: Japan Country of publication: United States