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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Palaniyandi, Suresh Selvaraj ; Batista Ferreira, Julio Cesar [1] ; Brum, Patricia Chakur [1] ; Mochly-Rosen, Daria [2]
Total Authors: 4
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE; v. 15, n. 8, p. 1769-1777, AUG 2011.
Web of Science Citations: 15
Abstract

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)

FAPESP's process: 06/56321-6 - Involvement of protein kinase C βII and ε isoforms in heart failure induced by myocardial infarction
Grantee:Julio Cesar Batista Ferreira
Support type: Scholarships in Brazil - Doctorate