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

促红细胞生成素（EPO）已被证明具有非促红细胞生成素，组织保护作用，尽管促红细胞生成素的血栓前作用阻碍了其临床应用。最近，我们证明了一种不具有血栓前作用的EPO受体激动剂（HBSP）可以抑制Watanabe遗传性高脂血症自发性心肌梗死（WHHLMI）兔的冠状动脉粥样硬化。在本研究中，我们研究了焦谷氨酸HBSP （ARA290）对巨噬细胞泡沫细胞形成的影响。ARA290通过上调ABCA1的表达来显著抑制它，而ABCA1在载脂蛋白E缺乏小鼠的胆固醇逆向转运和主动脉斑块面积减少中起关键作用。由于ARA290在化学上比HBSP更稳定，它可能是一种治疗动脉粥样硬化的有前景的药物。

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.