Expression of procollagen C-proteinase enhancer-1 in the remodeling rat heart is stimulated by aldosterone

Gania Kessler-Icekson*, Hadassa Schlesinger, Sarit Freimann, Efrat Kessler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Excessive collagen deposition is a common complication of myocardial infarction that causes progressive heart disease. Several pro-fibrotic cytokines and hormones, including aldosterone, control this process. Procollagen processing by procollagen C-proteinase(s) is critical for collagen deposition and is potentiated by procollagen C-proteinase enhancer proteins (PCPEs). We have shown previously that, in addition to stimulation of collagen I expression, aldosterone increases PCPE-1 expression in cultured heart fibroblasts. The present study was designed to examine whether aldosterone acts similarly in vivo. Rats underwent coronary artery ligation to induce myocardial infarction. They were then left either untreated (control) or treated with spironolactone (an aldosterone receptor antagonist) for 5 weeks when they were sacrificed and their hearts removed for analysis. In situ hybridization co-localized PCPE-1 and collagen I mRNAs to fibroblasts surrounding the scar region and adjacent blood vessels. The levels of both transcripts in the remodeling myocardium of untreated rats increased twofold as compared to sham-operated controls, an increase greatly reduced by spironolactone. Correspondingly, a 2-5 fold increase in PCPE-1 and collagen I was observed in the hearts of untreated rats as compared to both the spironolactone-treated and sham-operated controls. The results establish aldosterone as a physiological stimulator of PCPE-1 expression in the remodeling myocardium after infarction. Since PCPE-1 itself is a positive regulator of collagen deposition, this finding suggests PCPE-1 as a new potential target for intervention with cardiac fibrosis.

Original languageEnglish
Pages (from-to)358-365
Number of pages8
JournalInternational Journal of Biochemistry and Cell Biology
Volume38
Issue number3
DOIs
StatePublished - Mar 2006

Funding

FundersFunder number
German-Israeli Ministries of Science and TechnologyGR01355
Slezak Super-Center
Tel-Aviv University
German-Israeli Foundation for Scientific Research and DevelopmentI-141-202.01/96
Israel Science Foundation426/98, 736/01

    Keywords

    • Collagen
    • Fibrosis
    • Myocardial infarction
    • Procollagen C-proteinase enhancer
    • Rat

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