Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples Federico II, Naples, Italy.
Thromb Haemost. 2010 May;103(5):1065-75. doi: 10.1160/TH09-06-0392. Epub 2010 Feb 19.
Adipocytes are nowadays recognised as cells able to produce and secrete a large variety of active substances termed adipokines, which exert direct effects on vascular cells. Among these adipokines, leptin has been proposed to play a role in the pathophysiology of acute coronary syndromes, as well as in increasing cardiovascular risk. At the moment, however, the mechanisms linking leptin to cardiovascular disease are not completely understood. This study investigates the effects of leptin, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk or measurable in patients with acute coronary syndromes, on tissue factor (TF) and cellular adhesion molecules (CAMs) expression in human coronary endothelial cells (HCAECs). We demonstrate that leptin induces transcription of mRNA for TF and CAMs by real-time PCR. In addition, we show that this adipokine promotes surface expression of TF and CAMs that are functionally active since we observed increased procoagulant activity and leukocyte adhesion on cell surface. Leptin effects appear modulated by eNOS-production of oxygen free radicals through the activation of the transcription factor, nuclear factor(NF)-kappaB, since L-NAME, Superoxide Dismutase and NF-kappaB inhibitors suppressed CAMs and TF expression. Data of the present study, although in vitro , indicate that leptin may exert direct effects on human coronary endothelial cells by promoting CAMs and TF expression and support the hypothesis that this adipokines, besides being involved in the pathophysiology of obesity, might play a relevant role as an active mediator linking obesity to cardiovascular disease.
脂肪细胞现在被认为是能够产生和分泌多种被称为脂联素的活性物质的细胞，这些物质对血管细胞发挥直接作用。在这些脂联素中，瘦素被认为在急性冠状动脉综合征的病理生理学以及增加心血管风险中发挥作用。然而，目前将瘦素与心血管疾病联系起来的机制尚不完全清楚。本研究旨在探讨瘦素（在通常存在于心血管风险增加患者血浆中的浓度范围内，或在急性冠状动脉综合征患者中可测量）对人冠状动脉内皮细胞（HCAEC）中组织因子（TF）和细胞黏附分子（CAMs）表达的影响。我们证明瘦素通过实时 PCR 诱导 TF 和 CAMs 的 mRNA 转录。此外，我们还表明，这种脂肪细胞因子通过激活转录因子核因子（NF）-κB 促进 TF 和 CAMs 的表面表达，这些细胞因子具有功能活性，因为我们观察到细胞表面的促凝血活性和白细胞黏附增加。瘦素的作用似乎通过 eNOS 产生的氧自由基来调节，通过激活转录因子 NF-κB，因为 L-NAME、超氧化物歧化酶和 NF-κB 抑制剂抑制了 CAMs 和 TF 的表达。本研究的数据虽然是在体外进行的，但表明瘦素可能通过促进 CAMs 和 TF 的表达对人冠状动脉内皮细胞产生直接作用，并支持这样一种假设，即这种脂肪细胞因子除了参与肥胖的病理生理学之外，还可能作为一种将肥胖与心血管疾病联系起来的活跃介质发挥相关作用。
