Kellokoski Eija, Kunnari Anne, Jokela Maarit, Mäkelä Sanna, Kesäniemi Y Antero, Hörkkö Sohvi
Department of Internal Medicine and Biocenter Oulu, Institute of Clinical Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland.
Metabolism. 2009 Nov;58(11):1572-80. doi: 10.1016/j.metabol.2009.05.009. Epub 2009 Jul 15.
Emerging evidence indicates the potential involvement of ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, in low-grade inflammatory diseases such as obesity and atherosclerosis. The goal of the present study was to use cell culture models to investigate the influences of ghrelin and obestatin in processes participating in atherogenesis. We studied monocyte adhesion, monocyte chemoattractant protein-1, and adhesion molecule expression on endothelial cells as well as binding of oxidized low-density lipoprotein (LDL) and acetylated LDL to macrophages. Ghrelin treatment increased adhesion of calcein-labeled THP-1 monocytes to EA.hy 926 endothelial cells. Simultaneously, ghrelin increased the expression of intercellular adhesion molecule-1 measured by quantitative reverse transcriptase polymerase chain reaction. Tumor necrosis factor-alpha stimulation together with ghrelin treatment decreased both monocyte adhesion and vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 expression and, together with obestatin treatment, decreased vascular cell adhesion molecule-1 expression. Finally, ghrelin and obestatin increased binding of oxidized LDL to thioglycollate-elicited mouse peritoneal macrophages. No changes were observed in the uptake of acetylated LDL by mouse J774.A1 macrophages after exposure to ghrelin or obestatin. In conclusion, we found 3 lines of in vitro evidence supporting proatherogenic properties of ghrelin in the early stages of the disease. However, in the presence of tumor necrosis factor-alpha stimulation, opposite effects of ghrelin were observed, suggesting that ghrelin may also have an anti-inflammatory role in the presence of increased inflammation, for example, during the more progressed phases of atherogenesis.
新出现的证据表明，胃饥饿素（一种生长激素促分泌素受体的内源性配体）可能参与肥胖和动脉粥样硬化等低度炎症性疾病。本研究的目的是使用细胞培养模型来研究胃饥饿素和肥胖抑制素在参与动脉粥样硬化形成过程中的影响。我们研究了单核细胞黏附、单核细胞趋化蛋白-1以及内皮细胞上黏附分子的表达，以及氧化型低密度脂蛋白（LDL）和乙酰化LDL与巨噬细胞的结合。胃饥饿素处理增加了钙黄绿素标记的THP-1单核细胞与EA.hy 926内皮细胞的黏附。同时，胃饥饿素通过定量逆转录聚合酶链反应检测增加了细胞间黏附分子-1的表达。肿瘤坏死因子-α刺激与胃饥饿素处理共同降低了单核细胞黏附以及血管细胞黏附分子-1和单核细胞趋化蛋白-1的表达，而与肥胖抑制素处理共同降低了血管细胞黏附分子-1的表达。最后，胃饥饿素和肥胖抑制素增加了氧化型LDL与巯基乙酸诱导的小鼠腹腔巨噬细胞的结合。在胃饥饿素或肥胖抑制素处理后，小鼠J774.A1巨噬细胞对乙酰化LDL的摄取未观察到变化。总之，我们发现了三条体外证据支持胃饥饿素在疾病早期具有促动脉粥样硬化的特性。然而，在肿瘤坏死因子-α刺激存在的情况下，观察到胃饥饿素具有相反的作用，这表明在炎症增加的情况下，例如在动脉粥样硬化进展更明显的阶段，胃饥饿素可能也具有抗炎作用。
