Cardiovascular side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), which all inhibit cyclooxygenase (COX)-2, have prevented development of new drugs that target prostaglandins to treat inflammation and cancer. Microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors have efficacy in the NSAID arena but their cardiovascular safety is not known. Our previous work identified asymmetric dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase, as a potential biomarker of cardiovascular toxicity associated with blockade of COX-2. Here, we have used pharmacological tools and genetically modified mice to delineate mPGES-1 and COX-2 in the regulation of ADMA.

中文翻译：

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心血管 mPGES-1/COX-2/ADMA 轴的机械定义。


非甾体类抗炎药 (NSAID) 都会抑制环氧合酶 (COX)-2，引起的心血管副作用阻碍了针对前列腺素治疗炎症和癌症的新药的开发。微粒体前列腺素 E 合酶 1 (mPGES-1) 抑制剂在 NSAID 领域具有疗效，但其心血管安全性尚不清楚。我们之前的工作确定了不对称二甲基精氨酸 (ADMA)（一种内皮一氧化氮合酶抑制剂）作为与 COX-2 阻断相关的心血管毒性的潜在生物标志物。在这里，我们使用药理学工具和转基因小鼠来描述 mPGES-1 和 COX-2 对 ADMA 的调节。