Chronic erythropoietin treatment affects different molecular pathways of diabetic cardiomyopathy in mouse.
BACKGROUND
Recent studies in mice experimental models with acute ischaemic injury revealed that erythropoietin (EPO) has numerous tissue-protective effects in the heart, brain and kidneys. We therefore explored the tissue-protective properties of chronic EPO treatment in an experimental model of the db/db mouse with diabetic heart injury.


METHODS
We randomly treated 11 db/db mice with placebo (saline), 0.4 microg of the continuous erythropoietin receptor activator (CERA) per week (n = 11) or 1.2 microg CERA per week (n = 11) for 14 weeks, and analysed cardiac tissue. The lower CERA dose was a non-haematologically effective dose, whereas the second increased the haematocrit.


RESULTS
Compared with mice in the placebo group, CERA-treated mice had a reduction in TGF-beta(1) and collagen I expression in cardiac tissue (P < 0.01 vs. higher dose CERA). In addition, an increased expression of the pro-survival intracellular pathway p-AKT was observed (P < 0.05 vs. higher dose CERA). The values for the lower C.E.R.A had an intermediate nonsignificant effect. Furthermore, we were able to show that atrial natriuretic peptide (ANP) expression was increased in both CERA groups.


CONCLUSIONS
Chronic treatment with CERA protects cardiac tissue in diabetic animals, i.e. it inhibits molecular pathways of cardiac fibrosis, and the effects are dose-dependent.
Shushakova
N
N
Department of Internal Medicine, Hanover Medical School, Hanover, Germany.
Park
J K
JK
Menne
J
J
Fliser
D
D
D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins
D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols