Simultaneous administration of insulin-like growth factor-1 and darbepoetin alfa protects the rat myocardium against myocardial infarction and enhances angiogenesis.
Recent studies have shown that insulin growth factor-1 (IGF-1) and either erythropoietin (EPO) or the long-acting EPO analog Darbepoetin alfa (DA) protect the heart against ischemia/reperfusion (I/R) and myocardial infarction (MI). The present study examined the cardioprotective effect of simultaneous treatments with IGF-1 and DA in these models of cardiac injury. Rats were subjected to I/R or MI and were treated with IGF-1, DA, and a combination of IGF-1 and DA, or vehicle treatment. IGF-1 and DA treatments imparted similar protective effect by reducing infarct size. Moreover, these treatments led to improvement of cardiac function after I/R or MI compared to vehicle. In the reperfused heart, apoptosis was reduced with either or both IGF-1 and DA treatments as measured by reduced TUNEL staining and caspase-3 activity. In addition, after MI, treatment with IGF-1 or DA significantly induced angiogenesis. This angiogenic effect was enhanced significantly when IGF-1 and DA were given simultaneously compared to vehicle or either agents alone. These data indicate simultaneous pharmacological treatments with IGF-1 and DA protect the heart against I/R and MI injuries. This protection results in reduced infarct size and improved cardiac function. Moreover, this treatment reduces apoptosis and enhances angiogenesis in the ischemic heart.
Boucher
Matthieu
M
George Zallie and Family Laboratory for Cardiovascular Gene Therapy, Center for Translational Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Pesant
Stéphanie
S
Lei
Yong Hong
YH
Nanton
Natasha
N
Most
Patrick
P
Eckhart
Andrea D
AD
Koch
Walter J
WJ
Gao
Erhe
E
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008297:Male; D008954:Models, Biological; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000473:pathology*; D009206:Myocardium; D009389:Neovascularization, Pathologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*
D004921:Erythropoietin; D000068256:Darbepoetin alfa; D007334:Insulin-Like Growth Factor I; D053148:Caspase 3