van Oostrom Antonie J H H M, van Wijk Jeroen, Cabezas Manuel Castro
Departments of Internal Medicine and Endocrinology, University Medical Centre Utrecht, The Netherlands.
Drugs. 2004;64 Suppl 2:19-41. doi: 10.2165/00003495-200464002-00004.
Atherosclerosis is the major cause of death in the world. Fasting and postprandial hyperlipidaemia are important risk factors for coronary heart disease (CHD). Recent developments have undoubtedly indicated that inflammation is pathophysiologically closely linked to atherogenesis and its clinical consequences. Inflammatory markers such as C-reactive protein (CRP), leucocyte count and complement component 3 (C3) have been linked to CHD and to hyperlipidaemia and several other CHD risk factors. Increases in these markers may result from activation of endothelial cells (CRP, leucocytes, C3), disturbances in adipose tissue fatty acid metabolism (CRP, C3), or from direct effects of CHD risk factors (leucocytes). It has been shown that lipoproteins, triglycerides, fatty acids and glucose can activate endothelial cells, most probably as a result of the production of reactive oxygen species. Similar mechanisms may also lead to leucocyte activation. Increases in triglycerides, fatty acids and glucose are common disturbances in the metabolic syndrome and are most prominent in the postprandial phase. People are in a postprandial state most of the day, and this phase is proatherogenic. Inhibition of the activation of leucocytes, endothelial cells, or both, is an interesting target for intervention, as activation is obligatory for adherence of leucocytes to the endothelium, thereby initiating atherogenesis. Potential interventions include the use of unsaturated long-chain fatty acids, polyphenols, antioxidants, angiotensin converting enzyme inhibitors and high-dose aspirin, which have direct anti-inflammatory and antiatherogenic effects. Furthermore, peroxisome proliferator activating receptor gamma (PPARgamma) agonists and statins have similar properties, which are in part independent of their lipid-lowering effects.
动脉粥样硬化是全球主要的死亡原因。空腹和餐后高脂血症是冠心病（CHD）的重要危险因素。最近的研究进展无疑表明，炎症在病理生理上与动脉粥样硬化及其临床后果密切相关。炎症标志物如C反应蛋白（CRP）、白细胞计数和补体成分3（C3）已与冠心病、高脂血症及其他几种冠心病危险因素相关联。这些标志物的升高可能源于内皮细胞的激活（CRP、白细胞、C3）、脂肪组织脂肪酸代谢紊乱（CRP、C3）或冠心病危险因素的直接作用（白细胞）。研究表明，脂蛋白、甘油三酯、脂肪酸和葡萄糖可激活内皮细胞，这很可能是活性氧产生的结果。类似的机制也可能导致白细胞激活。甘油三酯、脂肪酸和葡萄糖的升高是代谢综合征中常见的紊乱情况，且在餐后阶段最为显著。人们一天中大部分时间处于餐后状态，而这个阶段具有促动脉粥样硬化作用。抑制白细胞或内皮细胞或两者的激活是一个有趣的干预靶点，因为激活是白细胞黏附于内皮从而启动动脉粥样硬化的必要条件。潜在的干预措施包括使用不饱和长链脂肪酸、多酚、抗氧化剂、血管紧张素转换酶抑制剂和大剂量阿司匹林，它们具有直接的抗炎和抗动脉粥样硬化作用。此外，过氧化物酶体增殖物激活受体γ（PPARγ）激动剂和他汀类药物也有类似特性，其部分作用独立于降脂效果。
