Pharmacological inhibition of beta IIPKC is cardioprotective in late-stage hypertrophy

Autor(es)

Ferreira, Julio C. B. ^[1] ; Koyanagi, Tomoyoshi ; Palaniyandi, Suresh S. ; Fajardo, Giovanni ^[2] ; Churchill, Eric N. ; Budas, Grant ; Disatnik, Marie-Helene ; Bernstein, Daniel ^[2] ; Brum, Patricia C. ^[1] ; Mochly-Rosen, Daria ^[3]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Phys Educ & Sport, BR-05508900 Sao Paulo - Brazil

^[2] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 - USA

^[3] Stanford Univ, Sch Med, Dept Chem & Syst Biol, CCSR, Stanford, CA 94305 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY; v. 51, n. 6, p. 980-987, DEC 2011.
• Citações Web of Science: 24

Resumo

We previously found that in the hearts of hypertensive Dahl salt-sensitive rats, beta IIPKC levels increase during the transition from compensated cardiac hypertrophy to cardiac dysfunction. Here we showed that a six-week treatment of these hypertensive rats with a beta IIPKC-specific inhibitor, beta IIV5-3, prolonged their survival by at least 6 weeks, suppressed myocardial fibrosis and inflammation, and delayed the transition from compensated hypertrophy to cardiac dysfunction. In addition, changes in the levels of the Ca(2+)-handling proteins, SERCA2 and the Na(+)/Ca(2+) exchanger, as well as troponin I phosphorylation, seen in the control-treated hypertensive rats were not observed in the beta IIPKC-treated rats, suggesting that beta IIPKC contributes to the regulation of calcium levels in the myocardium. In contrast, treatment with the selective inhibitor of beta IPKC, an alternative spliced form of beta IIPKC, had no beneficial effects in these rats. We also found that beta IIV5-3, but not beta IV5-3, improved calcium handling in isolated rat cardiomyocytes and enhanced contractility in isolated rat hearts. In conclusion, our data using an in vivo model of cardiac dysfunction (late-phase hypertrophy), suggest that beta IIPKC contributes to the pathology associated with heart failure and thus an inhibitor of beta IIPKC may be a potential treatment for this disease. (C) 2011 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 09/03143-1 - Controle de qualidade de proteína na insuficiência cardíaca: papel das diferentes isoformas de proteína quinase C
• Beneficiário: Julio Cesar Batista Ferreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado