Reiss Allison B, Edelman Sari D
Department of Medicine, Vascular Biology Institute, Winthrop-University Hospital, 222 Station Plaza, North Mineola, NY 11501, USA.
Curr Vasc Pharmacol. 2006 Oct;4(4):395-408. doi: 10.2174/157016106778521652.
Atherosclerosis is characterized by chronic inflammation and enrichment of inflammatory cells in the vessel wall. Acute inflammation can lead to damaged endothelium triggering the coagulation cascade and thrombus formation. Likewise, the clotting cascade may elicit an inflammatory response. The vascular endothelium regulates vascular tone, permeability, inflammation, thrombosis, and coagulation. Dysfunction of the vascular endothelium can promote atherosclerotic disease processes. Prostanoids (prostaglandins, thromboxane, and prostacyclin) have been established as inflammatory mediators in vascular endothelial function and there continues to be growing insights into their role in atherosclerotic disease. This review examines the role of prostanoids as paracrine inflammatory mediators of atherosclerotic vascular disease, highlighting the relevant physiology of eicosanoid production and endothelial dysfunction. We consider the role of prostanoids in systemic diseases associated with high cardiovascular morbidity and mortality, including diabetes mellitus, coronary artery disease, peripheral arterial disease, rheumatologic disorders, and dyslipidemia. We present emerging evidence that cardio-protective and lipid lowering medications, such as irbesartan and simvastatin may exert their effects via prostanoid mediated pathways. Both serum and urinary prostanoids may be utilized as diagnostic predictors of disease; for example 8-iso-PGF(2alpha) in the serum has recently been reported as an independent predictor of symptomatic peripheral arterial disease. In addition, we discuss current recommendations on established therapeutic uses of prostanoids for atherosclerotic diseases, such as the use of PGE(1) for the treatment of peripheral arterial disease. Finally, we investigate original therapeutic modalities of various prostanoids involved in the aforementioned diseases.
动脉粥样硬化的特征是血管壁的慢性炎症以及炎症细胞的富集。急性炎症可导致内皮损伤，触发凝血级联反应和血栓形成。同样，凝血级联反应也可能引发炎症反应。血管内皮调节血管张力、通透性、炎症、血栓形成和凝血。血管内皮功能障碍可促进动脉粥样硬化疾病进程。前列腺素（前列腺素、血栓素和前列环素）已被确认为血管内皮功能中的炎症介质，并且人们对它们在动脉粥样硬化疾病中的作用的认识不断深入。这篇综述探讨了前列腺素作为动脉粥样硬化性血管疾病旁分泌炎症介质的作用，强调了类花生酸生成和内皮功能障碍的相关生理学。我们考虑了前列腺素在与高心血管发病率和死亡率相关的全身性疾病中的作用，包括糖尿病、冠状动脉疾病、外周动脉疾病、风湿性疾病和血脂异常。我们提出了新的证据，表明具有心脏保护作用和降脂作用的药物，如厄贝沙坦和辛伐他汀，可能通过前列腺素介导的途径发挥作用。血清和尿液中的前列腺素都可作为疾病的诊断预测指标；例如，血清中的8-异前列腺素F2α最近被报道为有症状外周动脉疾病的独立预测指标。此外，我们讨论了关于前列腺素在动脉粥样硬化疾病既定治疗用途的当前建议，如使用前列腺素E1治疗外周动脉疾病。最后，我们研究了参与上述疾病的各种前列腺素的原始治疗方式。
