Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10954341 | Journal of Molecular and Cellular Cardiology | 2005 | 9 Pages |
Abstract
Despite current therapies, chronic heart failure (CHF) remains a major complication of myocardial infarction (MI). The pathological changes that follow MI extend to regions remote from the site of infarction (non-infarct zone, NIZ) where fibrosis is a prominent finding. Although the mechanisms underling this adverse remodeling are incompletely understood, activation of protein kinase C has recently been implicated in its pathogenesis. MI was induced in Sprague-Dawley rats by ligation of the left anterior descending coronary artery. One week post-MI, animals were randomized to receive the PKC-inhibitor, ruboxistaurin (LY333531) for 4 weeks, or no treatment. When compared with sham-operated animals, post-MI rats showed a 33 ± 7% reduction in fractional shortening over a 4 weeks period, that was attenuated by treatment with ruboxistaurin (6 ± 11%, P < 0.05). Increased matrix deposition was noted in the NIZ, particularly in the subendocardial region of post-MI rats, in association with elevated expression of the profibrotic growth factor, transforming growth factor-beta. These findings were also significantly reduced by ruboxistaurin. PKC-inhibition with ruboxistaurin led to attenuation in both the pathological fibrosis and impaired cardiac function that follow experimental MI, suggesting a possible role for this agent in preventing post-infarction heart failure.
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Authors
Andrew J. Boyle, Darren J. Kelly, Yuan Zhang, Alison J. Cox, Renae M. Gow, Kerrie Way, Silviu Itescu, Henry Krum, Richard E. Gilbert,