Louden Calvert, Brott David, Katein Anne, Kelly Thomas, Gould Sarah, Jones Huw, Betton Graham, Valetin Jean-Pierre, Richardson Rudy J
Department of Safety Assessment, AstraZeneca Pharmaceuticals, Cheshire, UK.
Toxicol Pathol. 2006;34(1):19-26. doi: 10.1080/01926230500512076.
In preclinical safety studies, drug-induced vascular injury can negatively impact candidate-drug selection because there are no obvious diagnostic markers for monitoring this pathology preclinically or clinically. Furthermore, our current understanding of the pathogenesis of this lesion is limited. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary target cells, smooth muscle (SMC) and endothelial cell (EC), are unknown. Evaluation of potential novel markers for clinical monitoring with a mechanistic underpinning would add value in risk assessment and risk management. This mini review focuses on the efforts and progress to identify diagnostic markers as well as understanding the mechanism of action in nonrodent drug-induced vascular injury.
在临床前安全性研究中，药物诱导的血管损伤会对候选药物的选择产生负面影响，因为在临床前或临床阶段均没有明显的诊断标志物来监测这种病理情况。此外，我们目前对这种病变发病机制的了解有限。虽然血管舒张和剪切应力增加似乎起了一定作用，但对主要靶细胞，即平滑肌细胞（SMC）和内皮细胞（EC）的损伤的确切机制尚不清楚。评估具有机制基础的潜在新型临床监测标志物将为风险评估和风险管理增添价值。本综述聚焦于在非啮齿类动物药物诱导的血管损伤中识别诊断标志物以及了解其作用机制方面所做的工作和取得的进展。
