Gummesson Anders, Hagg Daniel, Olson Fredrik J, Hulthe Johannes, Carlsson Lena M S, Fagerberg Bjorn
Department of Molecular and Clinical Medicine, Center for Cardiovascular and Metabolic Research, The Sahlgrenska Academy at Gothenburg University, University of Gothenburg, Gothenburg, Sweden.
Scand J Clin Lab Invest. 2009;69(6):636-42. doi: 10.3109/00365510902912747.
Matrix metalloproteinase 9 (MMP-9) is overexpressed in atherosclerotic plaques and in many cancers, and has emerged as a potential circulating biomarker for such diseases. However, adipose tissue (AT) might also produce circulating MMP-9, thereby reducing the value of MMP-9 as a biomarker. The aim of this study was to evaluate the impact of AT on circulating MMP-9, and if the metabolic syndrome might have a modifying effect.
Gene expression of MMP-9 was measured in AT, isolated adipocytes, atherosclerotic plaques, macrophages and various other human tissues using real-time PCR. Relationships between plasma MMP-9 (ELISA), adiposity, and metabolic syndrome were analyzed in a population-based cohort of 61-year-old men (n=513). Both AT mRNA levels and circulating levels of MMP-9 were measured in obese subjects (n=40) with and without the metabolic syndrome, treated with a weight-reducing diet.
Bone marrow, atherosclerotic plaques and macrophages had considerably higher MMP-9 mRNA than subcutaneous AT and isolated adipocytes. Among the 61-year-old men, active plasma MMP-9 concentrations were associated with several metabolic syndrome factors, and inflammatory markers, but not body mass index (BMI). In obese patients with, but not without metabolic syndrome AT mRNA levels and circulating MMP-9 declined during weight reduction, but there was no association between changes in plasma MMP-9 and BMI.
The results show that adipose tissue per se is not associated with circulating MMP-9. Components of the metabolic syndrome, such as circulating insulin and glucose were related to plasma MMP-9 both in the observation and dietary weight loss studies.
基质金属蛋白酶9(MMP - 9)在动脉粥样硬化斑块和许多癌症中过度表达,并已成为这些疾病潜在的循环生物标志物。然而,脂肪组织(AT)也可能产生循环MMP - 9,从而降低MMP - 9作为生物标志物的价值。本研究的目的是评估脂肪组织对循环MMP - 9的影响,以及代谢综合征是否可能具有调节作用。
使用实时PCR测量脂肪组织、分离的脂肪细胞、动脉粥样硬化斑块、巨噬细胞和各种其他人体组织中MMP - 9的基因表达。在一个基于人群的61岁男性队列(n = 513)中分析血浆MMP - 9(酶联免疫吸附测定)、肥胖和代谢综合征之间的关系。在接受减重饮食治疗的有或无代谢综合征的肥胖受试者(n = 40)中测量脂肪组织mRNA水平和MMP - 9的循环水平。
骨髓、动脉粥样硬化斑块和巨噬细胞的MMP - 9 mRNA水平明显高于皮下脂肪组织和分离的脂肪细胞。在61岁男性中,活性血浆MMP - 9浓度与几种代谢综合征因素和炎症标志物相关,但与体重指数(BMI)无关。在有代谢综合征的肥胖患者中,而非无代谢综合征的肥胖患者中,减重期间脂肪组织mRNA水平和循环MMP - 9下降,但血浆MMP - 9的变化与BMI之间无关联。
结果表明,脂肪组织本身与循环MMP - 9无关。在观察性研究和饮食减重研究中,代谢综合征的组成部分,如循环胰岛素和葡萄糖,均与血浆MMP - 9相关。