环氧化原酶-2促进LDL受体缺乏小鼠早期动脉样硬化病变的形成
Michael E Burleigh1, Vladimir R Babaev, John A Oates
1Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tenn, USA.
Circulation
|April 17, 2002
概括
选择性循环氧化酶-2 (COX-2) 抑制可以减少小鼠早期动脉样硬化. 巨细胞的COX-2表达也有助于动脉样硬化的发展,支持抗炎症策略.
科学领域:
- 心血管研究研究心血管研究
- 炎症和免疫学 炎症和免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 动脉样硬化以炎症为特征.
- 循环氧化酶-2 (COX-2) 存在于动脉样硬化病变中,并促进炎症.
研究的目的:
- 为了研究选择性COX-2抑制是否减少LDL受体缺乏 (LDLR-/-) 小鼠的早期病变形成.
- 为了确定巨细胞的COX-2表达是否有助于LDLR-/-小鼠的腺体发生.
主要方法:
- 雄性LDLR-/-小鼠接受了罗菲科克西布或印莫他 (选择性COX-2抑制剂) 治疗,或接受胎儿肝细胞移植,以产生缺乏巨细胞COX-2的小鼠.
- 给小鼠食用西方饮食6-8周.
- 在大动脉中评估了动脉样硬化,并测量了血清脂质.
主要成果:
- 罗菲科西布和印米他辛治疗显著减少了大动脉动脉样硬化.
- 与对照组相比,缺乏巨细胞COX-2表达 (COX-2-/- --> LDLR-/-) 的小鼠发生动脉样硬化明显较少.
- 罗菲科克西布没有影响血小板血栓素的产生,但降低了尿中的前环素代谢物水平.
- 在这两项研究中,血清脂质水平在两组之间没有显著差异.
结论:
- 药理学和遗传学证据表明,COX-2在LDLR-/-小鼠中促进了早期动脉样硬化病变的形成.
- 这些发现支持抗炎方法在预防动脉样硬化的潜力.
相关概念视频
Inflammation
Overview
Coronary Artery Disease II: Pathophysiology
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...
Atherosclerosis I: Introduction
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...
Atherosclerosis II: Clinical Manifestations and Diagnostic Tests
Atherosclerosis is a progressive disorder that leads to the thickening and narrowing of arterial walls due to plaque buildup. This condition can cause various symptoms depending on the arteries affected:Coronary Artery Disease (CAD): This condition affects the coronary arteries and may lead to chest pain (angina), shortness of breath (dyspnea), heart attacks, and other heart disease symptoms.Cerebrovascular Disease: This affects blood flow to the brain, causing transient ischemic attacks (TIAs)...
Atherosclerosis III: Management
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...
Lipid Catabolism
Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...


