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首页> 外文期刊>International Journal of Vascular Medicine >Recent Advances in Pharmacotherapy Development for Abdominal Aortic Aneurysm
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Recent Advances in Pharmacotherapy Development for Abdominal Aortic Aneurysm

机译:腹主动脉瘤药物治疗的最新进展

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Abdominal aortic aneurysm (AAA) is a common disease causing segmental expansion and rupture of the aorta with a high mortality rate. The lack of nonsurgical treatment represents a large and unmet need in terms of pharmacotherapy. Advances in AAA research revealed that activation of inflammatory signaling pathways through proinflammatory mediators shifts the balance of extracellular matrix (ECM) metabolism toward tissue degradation. This idea is supported by experimental evidence in animal models that pharmacologic intervention at each pathological step can prevent AAA development. Previously, we identified c-Jun N-terminal kinase (JNK), a pro-inflammatory signaling molecule, as a therapeutic target for AAA. Abnormal activation of JNK in AAA tissue regulates multiple pathological processes in a coordinated manner. Pharmacologic inhibition of JNK tips the ECM balance back towards repair rather than degradation. Interventions targeting signaling molecules such as JNK in order to manipulate multiple pathological processes may be an ideal therapeutic strategy for AAA. Furthermore, the development of biomarkers as well as appropriate drug delivery systems is essential to produce clinically practical pharmacotherapy for AAA.
机译:腹主动脉瘤(AAA)是导致主动脉节段性扩张和破裂的常见疾病,死亡率很高。在药物治疗方面,缺乏非手术治疗代表了巨大且未得到满足的需求。 AAA研究的进展表明,通过促炎介质介导的发炎信号通路的激活将细胞外基质(ECM)代谢的平衡向组织降解转移。动物模型中的实验证据支持了这一观点,即在每个病理步骤进行药理干预可以阻止AAA的发展。以前,我们将促炎性信号分子c-Jun N末端激酶(JNK)确定为AAA的治疗靶标。 AAA组织中JNK的异常激活以协调的方式调节多种病理过程。 JNK的药理抑制作用使ECM平衡恢复到修复而非降解。为了操纵多种病理过程,靶向信号分子如JNK的干预可能是AAA的理想治疗策略。此外,生物标志物的开发以及合适的药物递送系统对于产生AAA的临床实用药物疗法至关重要。

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