Back to Search
Start Over
Asialoerythropoietin, a nonerythropoietic derivative of erythropoietin, displays broad anti-heart failure activity.
- Source :
-
Circulation. Heart failure [Circ Heart Fail] 2012 Mar 01; Vol. 5 (2), pp. 274-85. Date of Electronic Publication: 2012 Feb 16. - Publication Year :
- 2012
-
Abstract
- Background: We investigated the effects of asialoerythropoietin (asialoEPO), a nonerythrogenic erythropoietin derivative, on 3 murine models of heart failure with different etiologies.<br />Methods and Results: Doxorubicin (15 mg/kg) induced heart failure within 2 weeks (toxic cardiomyopathy). Treatment with asialoEPO (6.9 μg/kg) for 2 weeks thereafter attenuated the associated left ventricular dysfunction and dilatation. In addition, the asialoEPO-treated heart showed less myocardial fibrosis, inflammation, and oxidative damage, and diminished atrophic cardiomyocyte degeneration, which was accompanied by restored expression of GATA-4 and sarcomeric proteins. Mice with large 6-week-old myocardial infarctions exhibited marked left ventricular dysfunction with adverse remodeling (ischemic cardiomyopathy). AsialoEPO treatment for 4 weeks significantly mitigated progression of the dysfunction and remodeling and reduced myocardial fibrosis, inflammation, and oxidative damage. Finally, 25-week-old δ-sarcoglycan-deficient mice (genetic cardiomyopathy) were treated with asialoEPO for 5 weeks. AsialoEPO mitigated the progressive cardiac remodeling and dysfunction through cardiomyocyte hypertrophy, and upregulated expression of GATA-4 and sarcomeric proteins. AsialoEPO appears to act by altering the activity of the downstream erythropoietin receptor signals extracellular signal-regulated protein kinase, Akt, signal transducer, and activator of transcription 3 and 5 in a model-specific manner.<br />Conclusions: The findings suggest that asialoEPO exerts broad cardioprotective effects through distinct mechanisms depending on the model, which are independent of the erythrogenic action. This compound may be promising for the treatment of heart failure of various etiologies.
- Subjects :
- Animals
Asialoglycoproteins administration & dosage
Disease Models, Animal
Dose-Response Relationship, Drug
Erythropoietin administration & dosage
Erythropoietin therapeutic use
Follow-Up Studies
Heart Failure physiopathology
Mice
Mice, Inbred C57BL
Treatment Outcome
Ventricular Function, Left physiology
Asialoglycoproteins therapeutic use
Erythropoietin analogs & derivatives
Heart Failure drug therapy
Ventricular Function, Left drug effects
Ventricular Remodeling drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1941-3297
- Volume :
- 5
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Circulation. Heart failure
- Publication Type :
- Academic Journal
- Accession number :
- 22343033
- Full Text :
- https://doi.org/10.1161/CIRCHEARTFAILURE.111.965061