Abstract:
OBJECTIVES:We examined the effect of asialoerythropoietin (asialoEPO), a nonerythrogenic derivative of erythropoietin (EPO), on renal dysfunction-associated heart failure. BACKGROUND:Although EPO is known to exert beneficial effects on cardiac function, the clinical benefits in patients with chronic kidney disease are controversial. It remains to be addressed whether previously reported outcomes were the result of relief of the anemia, adverse effects of EPO, or direct cardiovascular effects. METHODS:Mice underwent 5/6 nephrectomy to cause renal dysfunction. Eight weeks later, when renal dysfunction was established, anemia and cardiac dysfunction and remodeling were apparent. Mice were then assigned to receive saline (control), recombinant human erythropoietin (rhEPO) at 5,000 IU (714 pmol)/kg, or asialoEPO at 714 pmol/kg, twice/week for 4 weeks. RESULTS:Although only rhEPO relieved the nephrectomy-induced anemia, both rhEPO and asialoEPO significantly and similarly mitigated left ventricular dilation and dysfunction. The hearts of rhEPO- or asialoEPO-treated mice showed less hypertrophy, reflecting decreases in cardiomyocyte hypertrophy and degenerative subcellular changes, as well as significant attenuation of fibrosis, leukocyte infiltration, and oxidative deoxyribonucleic acid damage. These phenotypes were accompanied by restored expression of GATA-4, sarcomeric proteins, and vascular endothelial growth factor and decreased inflammatory cytokines and lipid peroxidation. Finally, myocardial activation was observed of extracellular signal-regulated protein kinase and signal transducer and activator of transcription pathways in the treated mice. CONCLUSIONS:EPO receptor signaling exerts direct cardioprotection in an animal model of renal dysfunction-associated heart failure, probably by mitigating degenerative, pro-fibrosis, inflammatory, and oxidative processes but not through relief of anemia.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Ogino A,Takemura G,Kawasaki M,Tsujimoto A,Kanamori H,Li L,Goto K,Maruyama R,Kawamura I,Takeyama T,Kawaguchi T,Watanabe T,Moriguchi Y,Saito H,Fujiwara T,Fujiwara H,Minatoguchi Sdoi
10.1016/j.jacc.2010.04.068subject
Has Abstractpub_date
2010-11-30 00:00:00pages
1949-58issue
23eissn
0735-1097issn
1558-3597pii
S0735-1097(10)03975-6journal_volume
56pub_type
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