诱导口服耐受氧化低密度脂蛋白可以改善动脉样硬化
G H M van Puijvelde1, A D Hauer, P de Vos
1Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands. puijvelde@lacdr.leidenuniv.nl
Circulation
|October 25, 2006
概括
口服氧化低密度脂蛋白 (oxLDL) 诱导耐受性,减少小鼠动脉样硬化发展. 这涉及激活调节性T细胞,这表明了对动脉样硬化的潜在新疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 氧化低密度脂蛋白 (oxLDL) 通过巨细胞的处理激活T细胞,导致动脉样硬化.
- 口服耐受性诱导和调控性T细胞激活为动脉样硬化提供了潜在的治疗策略.
研究的目的:
- 研究使用oxLDL进行口服耐受性诱导的疗效,以预防和治疗动脉样硬化.
- 探索调节性T细胞在oxLDL诱导的口服耐受性中的作用及其对动脉动脉产生的影响.
主要方法:
- 在LDL受体/-小鼠使用oxLDL或MDA-LDL在动脉形成前诱导的口服耐受性.
- 评估了口服耐受性对动脉样硬化的发病和进展的影响.
- 调节性T细胞群 (CD4+CD25+Foxp3+) 和它们的细胞因子产生 (TGF-β) 的量化变化.
- 在动脉样硬化斑块中分析了关键调节性T细胞标记物的mRNA表达 (Foxp3,CTLA-4,CD25).
主要成果:
- 在小鼠中,口服耐受性对oxLDL显著减弱动脉样硬化开始 (30-71%) 和进展 (45%).
- 诱导的耐受性导致和淋巴结中的CD4+ CD25+ Foxp3+细胞增加,增加了oxLDL特异性TGF-β的产生.
- 在oxLDL口服耐受后,斑块中观察到Foxp3,CTLA-4和CD25的mRNA表达增加.
- 对MDA-LDL的耐受性没有影响动脉动脉生成.
结论:
- 通过口服耐受激活的oxLDL特异性调节性T细胞可以抵消oxLDL特异性T细胞参与动脉样硬化.
- 对oxLDL的口服耐受性诱导是调节动脉动脉生成中的免疫反应的有希望的策略.
- 这种方法为治疗动脉样硬化提供了一个新的治疗途径.
相关概念视频
Inflammation
46.6K
Overview
46.6K
Radical Autoxidation
2.5K
The oxidation of an organic compound in the presence of air or oxygen is called autoxidation. For example, cumene reacts with oxygen to form hydroperoxide. Autoxidation involves initiation, propagation, and termination steps. Many organic compounds are susceptible to autoxidation—especially ethers in the presence of oxygen, which form hydroperoxides. Even though this reaction is slow, old ether bottles contain small amounts of peroxide, which leads to laboratory explosions during ether...
2.5K
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
1.7K
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
1.7K
Coronary Artery Disease II: Pathophysiology
1.1K
Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
1.1K
Atherosclerosis I: Introduction
2.5K
Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
2.5K
Atherosclerosis III: Management
741
Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
741


