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erythropoietin (rhEPO) would improve tissue repair in rat after myocardial
infarction (MI).
Methods and Results
RhEPO-producing cardiac ibroblasts were generated ex vivo by transduction
with retroviral vector. he anti-apoptotic efect of rhEPO-producing ibro-
blasts was evaluated by co-culture with rat neonatal cardiomyocytes exposed
to H2O2-induced oxidative stress. Annexin V/PI assay and DAPI staining
showed that compared with control, rhEPO forced expression markedly at-
tenuated apoptosis and improved survival of cultured cardiomyocytes. To test
the efect of rhEPO on the infarcted myocardium, Sprague-Dawley rats were
subjected to permanent coronary artery occlusion, and rhEPO-producing i-
broblasts, non-transduced ibroblasts, or saline, were injected into the scar tis-
sue seven days after infarction. One month later, immunostaining identiied
rhEPO expression in the implanted engineered cells but not in controls. Com-
pared with non-transduced ibroblasts or saline injection, implanted rhEPO-
producing ibroblasts promoted vascularization in the scar, and prevented cell
apoptosis. By two-dimensional echocardiography and postmortem morphom-
etry, transplanted EPO-engineered ibroblasts did not prevent left ventricular
(LV) dysfunction and adverse LV remodeling 5 and 9 weeks after MI.
Conclusion
In situ expression of rhEPO enhances vascularization and reduces cell apop-
tosis in the infarcted myocardium. However, local EPO therapy is insuicient
for functional improvement after MI in rat.
background
Erythropoietin (EPO), a hematopoietic cytokine, has been shown to possess
cardioprotective characteristics that can minimize ischemic injury and improve
myocardial viability and function [1]. Systemic administration of recombinant
human EPO (rhEPO) before or after myocardial ischemia reduces infarct size
and improves cardiac function [2,3]. he beneicial efects of EPO are mediated
by apoptosis inhibition, driven by Akt/phosphoinositide3-kinase signaling [4,5],
and neovascularization by stimulation of endothelial progenitor cells [6,7]. How-
ever, systemic administration of EPO to patients with coronary artery disease
could lead to adverse efects, such as high viscocity, impaired tissue perfusion,
high blood pressure and an increased incidence of thrombosis [8,9]. Hematocrit
elevation has been linked to excess mortality in patients with ischemic heart dis-
ease [10,11]. Over-expression of rhEPO in transgenic mice resulted in cardiac
dysfunction and reduced life span [12,13]. Overall, the potential adverse efects
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