Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithee Rd, BKK, Bangkok, 10400, Thailand.
Lipids Health Dis. 2013 Sep 8;12:132. doi: 10.1186/1476-511X-12-132.
Atherosclerosis is a chronic progressive inflammatory disease of blood vessels particularly the arteries. The development of atherosclerotic plaques or atherogenesis is a complex process that is influenced by cardiovascular risk factors such as vascular inflammation and dyslipidemia. This study demonstrates the ability of tumor necrosis factor-alpha (TNF-α) and low density lipoproteins (LDL) to induce atherosclerotic plaque in human saphenous vein (HSV) organ culture.
Normal HSV segments, from male patients who had coronary bypass graft, were cultured in DMEM containing 5% heat inactivated fetal bovine serum. TNF-α (5 ng/ml) was applied in combination with native LDL (nLDL) or oxidized LDL (oxLDL) at the dose of 50 μg/ml for 14 days. The phenotypic changes of the organ cultures characteristic of initial atherosclerotic plaques were evaluated. The effect of anti-atherogenic agent, 17-β estradiol (E2), was also determined.
Histologic, histomorphometric, and immunohistochemical examinations revealed that HSV rings stimulated with TNF-α + nLDL or TNF-α + oxLDL can exhibit the essential morphological features of atherogenesis, including fibrous cap formation, cholesterol clefts, evident thickening of the intimal layer, increased proliferation of smooth muscle cells (SMC) and migration to the subendothelial layer, significant SMC foam cell formation, and increased expression of adhesion molecules in the vascular wall. Addition of E2 (50 nM) to the culture significantly modulated the critical changes. Consistently, mRNA profiling of the HSV model revealed that 50 of 84 genes of atherosclerosis were up-regulated.
Phenotypic changes characteristic of the initial development of atherosclerotic plaques can be induced in HSV organ culture.
动脉粥样硬化是一种慢性进行性血管炎症性疾病，尤其是动脉。动脉粥样硬化斑块的形成或动脉粥样硬化发生是一个复杂的过程，受血管炎症和血脂异常等心血管危险因素的影响。本研究表明肿瘤坏死因子-α（TNF-α）和低密度脂蛋白（LDL）能够诱导人隐静脉（HSV）器官培养物中的动脉粥样硬化斑块形成。
从接受冠状动脉旁路移植术的男性患者中获取正常 HSV 节段，在含有 5%热灭活胎牛血清的 DMEM 中进行培养。将 TNF-α（5ng/ml）与天然 LDL（nLDL）或氧化 LDL（oxLDL）联合应用，剂量为 50μg/ml，培养 14 天。评估器官培养物中初始动脉粥样硬化斑块特征的表型变化。还确定了抗动脉粥样硬化剂 17-β 雌二醇（E2）的作用。
组织学、组织形态计量学和免疫组织化学检查显示，经 TNF-α+nLDL 或 TNF-α+oxLDL 刺激的 HSV 环可表现出动脉粥样硬化发生的基本形态特征，包括纤维帽形成、胆固醇裂隙、内膜层明显增厚、平滑肌细胞（SMC）增殖和向血管内膜下层迁移、明显的 SMC 泡沫细胞形成以及血管壁中粘附分子的表达增加。向培养物中添加 E2（50nM）可显著调节关键变化。一致地，HSV 模型的 mRNA 谱分析显示，84 个动脉粥样硬化基因中有 50 个上调。
HSV 器官培养物中可诱导出动脉粥样硬化初始发展特征的表型变化。
