University of Pennsylvania, Hospital of the University of Pennsylvania, Cardiovascular Institute, Cardiovascular Division, Philadelphia, PA 19104, USA.
Expert Opin Investig Drugs. 2010 Jan;19(1):161-8. doi: 10.1517/13543780903501513.
Atherosclerosis is an inflammatory-immune mediated disease process. Plaque rupture is responsible for the clinical events of ischemic death, myocardial infarction, acute coronary syndromes and ischemic strokes. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) seems to play a major role in the development of such high-risk lesions, in both the coronary and carotid arteries. Darapladib is a selective inhibitor of Lp-PLA(2).
An overview of darapladib by reviewing the studies (1990 - 2009) that have provided the rationale for the development of darapladib; and a discussion of its potential merit as a new therapeutic drug to target high-risk atherosclerosis.
The reader should gain an understanding of the importance of inflammation during atherogenesis as well as of the biology of Lp-PLA(2) and its proatherogenic role. Additional insights will be gained into the role of selective inhibitors of Lp-PLA(2) as new therapeutic agents.
Darapladib is a selective inhibitor of Lp-PLA(2) and represents a new class of therapeutic agents that target inflammation to treat high-risk atherosclerosis.
动脉粥样硬化是一种炎症免疫介导的疾病过程。斑块破裂是导致缺血性死亡、心肌梗死、急性冠脉综合征和缺血性中风等临床事件的原因。脂蛋白相关磷脂酶 A2（Lp-PLA2）似乎在冠状动脉和颈动脉等高危病变的发展中起主要作用。达拉普利是 Lp-PLA2 的选择性抑制剂。
通过回顾研究（1990-2009 年），概述达拉普利，这些研究为达拉普利的开发提供了依据；并讨论了它作为一种针对高危动脉粥样硬化的新型治疗药物的潜在价值。
读者应该了解在动脉粥样发生过程中炎症的重要性，以及 Lp-PLA2 的生物学及其促动脉粥样硬化作用。还将深入了解 Lp-PLA2 的选择性抑制剂作为新型治疗药物的作用。
达拉普利是 Lp-PLA2 的选择性抑制剂，代表了一类新的治疗药物，通过靶向炎症来治疗高危动脉粥样硬化。
