Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-5158, USA.
Trends Cardiovasc Med. 2010 Aug;20(6):189-95. doi: 10.1016/j.tcm.2011.04.002.
Both traditional and purpose-designed nonsteroidal anti-inflammatory drugs, selective for inhibition of cyclooxygenase (COX)-2, alleviate pain and inflammation but confer a cardiovascular hazard attributable to inhibition of COX-2-derived prostacyclin (PGI(2)). Deletion of microsomal PGE synthase-1 (mPGES-1), the dominant enzyme that converts the COX-derived intermediate product PGH(2) to PGE(2), modulates inflammatory pain in rodents. In contrast with COX-2 deletion or inhibition, PGI(2) formation is augmented in mPGES-1(-/-) mice-an effect that may confer cardiovascular benefit but may undermine the analgesic potential of inhibitors of this enzyme. This review considers the cardiovascular biology of mPGES1 and the complex challenge of developing inhibitors of this enzyme.
传统和专门设计的非甾体抗炎药，选择性抑制环氧化酶（COX）-2，可缓解疼痛和炎症，但会带来归因于 COX-2 衍生的前列环素（PGI（2））抑制的心血管风险。微粒体前列腺素 E 合酶-1（mPGES-1）的缺失，即将 COX 衍生的中间产物 PGH（2）转化为 PGE（2）的主要酶，调节啮齿动物的炎症性疼痛。与 COX-2 的缺失或抑制相反，mPGES-1（-/-）小鼠中 PGI（2）的形成增加 - 这种效应可能带来心血管益处，但可能会削弱该酶抑制剂的镇痛潜力。本文综述了 mPGES1 的心血管生物学以及开发该酶抑制剂的复杂挑战。
