Circulating insulin-like growth factor I (IGF-1) levels are closely associated with cardiac performance although the role of IGF-1 in alcoholic cardiac dysfunction is unknown.
This study was designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on chronic alcohol-induced cardiomyocyte contractile and intracellular Ca2+2+ properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-relengthening (TR90), change in fura-fluorescence intensity (ΔFFI) and intracellular Ca2+ decay.
Levels of apoptotic regulators Caspase-3, Bcl-2 and JNK, the ethanol metabolizing enzyme mitochondrial aldehyde dehydrogenase (ALDH2), as well as the cellular fuel gauge AMPK were evaluated.
Chronic alcohol intake enlarged myocyte cross-sectional area, reduced PS, ± dL/dt and ΔFFI as well as prolonged TR90 and intracellular Ca2+ decay, the effect of which was greatly attenuated by IGF-1 deficiency.
The beneficial effect of LID against alcoholic cardiac mechanical defect was ablated by IGF-1 replenishment. Alcohol intake increased Caspase-3 activity/expression while downregulated Bcl-2, ALDH2 and pAMPK without affecting JNK and AMPK. IGF-1 deficiency attenuated alcoholism-induced responses in all these proteins with the exception of Bcl-2.
In addition, the AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) abrogated short-term ethanol incubation-elicited cardiac mechanical dysfunction.
Taken together, these data suggested that IGF-1 deficiency may reduce the sensitivity to ethanol-induced myocardial mechanical dysfunction.
Our data further depicted a likely role of Caspase-3, ALDH2 and AMPK activation in IGF-1 deficiency-induced “desensitization” of alcoholic cardiomyopathy.
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