PKC beta II inhibition attenuates myocardial infarction induced heart failure and is associated with a reduction of fibrosis and pro-inflammatory responses

Autor(es)

Palaniyandi, Suresh Selvaraj ; Batista Ferreira, Julio Cesar ^[1] ; Brum, Patricia Chakur ^[1] ; Mochly-Rosen, Daria ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo - Brazil

^[2] Stanford Univ, Sch Med, Dept Chem & Syst Biol, CCSR, Stanford, CA 94305 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE; v. 15, n. 8, p. 1769-1777, AUG 2011.
• Citações Web of Science: 17

Resumo

Protein kinase C beta II (PKC beta II) levels increase in the myocardium of patients with end-stage heart failure (HF). Also targeted overexpression of PKC beta II in the myocardium of mice leads to dilated cardiomyopathy associated with inflammation, fibrosis and myocardial dysfunction. These reports suggest a deleterious role of PKC beta II in HF development. Using a post-myocardial infarction (MI) model of HF in rats, we determined the benefit of chronic inhibition of PKC beta II on the progression of HF over a period of 6 weeks after the onset of symptoms and the cellular basis for these effects. Four weeks after MI, rats with HF signs that were treated for 6 weeks with the PKC beta II selective inhibitor (beta IIV5-3 conjugated to TAT(47-57) carrier peptide) (3 mg/kg/day) showed improved fractional shortening (from 21% to 35%) compared to control (TAT(47-57) carrier peptide alone). Formalin-fixed mid-ventricle tissue sections stained with picrosirius red, haematoxylin and eosin and toluidine blue dyes exhibited a 150% decrease in collagen deposition, a two-fold decrease in inflammation and a 30% reduction in mast cell degranulation, respectively, in rat hearts treated with the selective PKC beta II inhibitor. Further, a 90% decrease in active TGF beta 1 and a significant reduction in SMAD2/3 phosphorylation indicated that the selective inhibition of PKC beta II attenuates cardiac remodelling mediated by the TGF-SMAD signalling pathway. Therefore, sustained selective inhibition of PKC beta II in a post-MI HF rat model improves cardiac function and is associated with inhibition of pathological myocardial remodelling. (AU)

• Processo FAPESP: 06/56321-6 - Participação das isoformas proteína quinase C βII e proteína quinase C ε na insuficiência cardíaca induzida por infarto do miocárdio
• Beneficiário: Julio Cesar Batista Ferreira
• Modalidade de apoio: Bolsas no Brasil - Doutorado