Molecular mechanisms of suppression of macrophage foam cell formation by an erythropoietin receptor agonist

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Erythropoietin (EPO) has been shown to have nonerythropoietic, tissue-protective effects although prothrombotic effects of EPO hamper its clinical use. Recently, we demonstrated that an EPO receptor agonist (HBSP) that does not have prothrombotic effects suppresses coronary atherosclerosis in Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits. In the present study, we examined the effects of pyroglutamate HBSP (ARA290) on macrophage foam cell formation. ARA290 significantly inhibited it by up-regulating the expression of ABCA1 that plays a pivotal role in reverse cholesterol transport and reduced aortic plaque area in apo E deficient mice. Because ARA290 is chemically more stable than HBSP, it may be a promising drug for treating atherosclerosis.