Clarification of molecular mechanism in anti-atherogenic action of an adipocytedrived matrix protein, adiponectin.

我们鉴定了一种新的脂肪细胞来源的基质蛋白，脂联素，它在血液循环中大量存在。我们发现肥胖者和冠状动脉疾病(CAD)患者的血浆脂联素浓度降低，体外研究表明，脂联素通过ICAM-1、VCAM-1和E-选择素等黏附分子的表达减少抑制单核细胞与内皮细胞的附着，这是动脉粥样硬化血管病变的早期事件。在本研究中，我们观察了血浆脂联素浓度与包括2型糖尿病在内的动脉粥样硬化易感疾病的关系，并阐明了其抗动脉粥样硬化作用的分子机制。此外，我们证实了许多肥胖者和冠心病患者的血浆脂联素浓度降低。此外，我们还证实了许多肥胖者和冠心病患者的血浆脂联素浓度降低我们观察到无冠心病的糖尿病患者的血浆脂联素水平低于年龄和体重指数匹配的非糖尿病患者。糖尿病合并冠心病患者的血浆脂联素水平低于糖尿病非冠心病患者。体重减少显著升高糖尿病患者和非糖尿病患者的血浆脂联素水平。我们先前观察到脂联素抑制肿瘤坏死因子-α(肿瘤坏死因子-α)诱导的内皮细胞黏附分子的表达。在本研究中，我们证实脂联素通过cAMP依赖的途径特异性地抑制肿瘤坏死因子-α诱导的人主动脉内皮细胞I-κB-α-NF-κB的激活。

We identified a novel adipocyte-derived matrix protein, adiponectin, which is abundantly present in the circulation. We showed that obese subjects and subjects with coroary artery disease (CAD) exhibited decreased plasma concentrations of adiponectin and also, in vitro study, that this protein suppressed the attachment of monocytes to endothelial cells through the decreased expression of adhesion molecules such as ICAM-1, VCAM-1, and E-selectin, which is an early event in atherosclerotic vascular change.In the present study, we observed the relationship between plasma adiponectin concentrations and disorders susceptible to atherosclerosis including type 2 diabetes, and aiso clarified the molecular mechanism in its anti-atherogenic actions.We confirmed that plasma adiponectin cncentrations were decreased in many obese subjects and the subjects with CAD.Furthermore, we observed plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in age- and BMI-matched non-diabetic subjects. The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD.Weight reduction significantly elevated plasma adiponectin levels in both the diabetic and the non-diabetic subjects.We previously observed that adiponectin inhibited tumor necrosis factor-α (TNF-α)-induced expression of endothelial adhesion molecules. In the current study, we demonstrated that adiponectin specifically supressed TNF-α-induced IκB-α-NFκB activation through a cAMP -dependent pathway in human aortic endothelial cells.