Alberti L, Gilardini L, Zulian A, Micheletto G, Peri G, Doni A, Mantovani A, Invitti C
Unit of Metabolic Diseases and Diabetes, Istituto Auxologico Italiano, Via Ariosto 13, 20145 Milan, Italy.
Atherosclerosis. 2009 Feb;202(2):455-60. doi: 10.1016/j.atherosclerosis.2008.05.015. Epub 2008 May 15.
Pentraxin 3 (PTX3) is an acute phase protein strongly expressed by advanced atherosclerotic lesions. We investigated (a) PTX3 expression and secretion in subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (VAT) obtained from 21 obese (37.4+/-8.15 yr) and 10 normal weight subjects (43.7+/-11.07 yr) and (b) the relationships of adipose PTX3 with tumour necrosis factor alpha (TNFalpha) and adiponectin expression and with cardiometabolic risk factors. Real-time PCR was used to quantify specific mRNA for PTX3, CD68 (macrophage marker), TNFalpha and adiponectin. Fresh adipose tissue was cultured and PTX3 measured in the medium. Serum insulin, glucose, HDL and LDL cholesterol, triglycerides, C-reactive protein (CRP), fibrinogen, adiponectin, TNFalpha and PTX3 were measured. PTX3 expression was similar in the two fat compartments and tended to be higher in obese than in normal weight subjects in VAT only (p=0.05). CD68 and PTX3 expressions were correlated with each other in SAT but not in VAT. After adjustment for age and sex, VAT-PTX3 expression and release were correlated with VAT-TNFalpha expression (p<0.01 for both) and with LDL/HDL ratio (p<0.01 and p<0.001). VAT-PTX3 expression was also correlated with BMI, triglycerides, CRP, fibrinogen and adiponectin (p<0.05 for all). In the multivariate analysis with VAT-PTX3 RNA levels as dependent variable, LDL/HDL ratio and fibrinogen remained independently associated with VAT-PTX3 expression (p<0.01 for both). These associations were not seen within SAT.
Human adipose tissue expresses and releases PTX3 likely under TNFalpha control. VAT production of PTX3 seems to contribute to the mechanisms underlying the development of atherosclerosis.
五聚体3(PTX3)是一种急性期蛋白,在晚期动脉粥样硬化病变中强烈表达。我们研究了:(a)从21名肥胖者(37.4±8.15岁)和10名正常体重者(43.7±11.07岁)获取的皮下脂肪组织(SAT)和网膜内脏脂肪组织(VAT)中PTX3的表达和分泌情况;(b)脂肪组织中PTX3与肿瘤坏死因子α(TNFα)、脂联素表达以及与心脏代谢危险因素之间的关系。采用实时定量PCR法对PTX3、CD68(巨噬细胞标志物)、TNFα和脂联素的特异性mRNA进行定量分析。将新鲜脂肪组织进行培养,并检测培养基中的PTX3含量。同时检测血清胰岛素、葡萄糖、高密度脂蛋白和低密度脂蛋白胆固醇、甘油三酯、C反应蛋白(CRP)、纤维蛋白原、脂联素、TNFα和PTX3。在两个脂肪组织中PTX3的表达相似,仅在VAT中肥胖者的PTX3表达倾向于高于正常体重者(p = 0.05)。在SAT中CD68和PTX3的表达相互相关,但在VAT中不相关。在对年龄和性别进行校正后,VAT - PTX3的表达和释放与VAT - TNFα的表达相关(两者p均<0.01),并与低密度脂蛋白/高密度脂蛋白比值相关(p<0.01和p<0.001)。VAT - PTX3的表达还与体重指数、甘油三酯、CRP、纤维蛋白原和脂联素相关(所有p均<0.05)。在以VAT - PTX3 RNA水平作为因变量的多变量分析中,低密度脂蛋白/高密度脂蛋白比值和纤维蛋白原仍与VAT - PTX3的表达独立相关(两者p均<0.01)。在SAT中未观察到这些相关性。
人体脂肪组织可能在TNFα的调控下表达并释放PTX3。VAT中PTX3的产生似乎参与了动脉粥样硬化发生发展的机制。