Open AccessSimultaneous Administration of Insulin‐Like Growth Factor‐1 and Darbepoetin Alfa Protects the Rat Myocardium Against Myocardial Infarction and Enhances Angiogenesis
Author(s) -
Boucher Matthieu,
Pesant Stéphanie,
Lei Yong Hong,
Nanton Natasha,
Most Patrick,
Eckhart Andrea D.,
Koch Walter J.,
Gao Erhe
Publication year - 2008
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2008.00008.x
Subject(s) - medicine , angiogenesis , myocardial infarction , darbepoetin alfa , erythropoietin , tunel assay , cardiac function curve , cardioprotection , pharmacology , ischemia , apoptosis , cardiology , infarction , endocrinology , heart failure , biology , immunohistochemistry , biochemistry
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.