Department of Projects Research, Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
Hypertens Res. 2022 Mar;45(3):389-400. doi: 10.1038/s41440-021-00806-y. Epub 2022 Jan 6.
Adrenomedullin (AM) is a vasodilative peptide with various physiological functions, including the maintenance of vascular tone and endothelial barrier function. AM levels are markedly increased during severe inflammation, such as that associated with sepsis; thus, AM is expected to be a useful clinical marker and therapeutic agent for inflammation. However, as the increase in AM levels in cardiovascular diseases (CVDs) is relatively low compared to that in infectious diseases, the value of AM as a marker of CVDs seems to be less important. Limitations pertaining to the administrative route and short half-life of AM in the bloodstream (<30 min) restrict the therapeutic applications of AM for CVDs. In early human studies, various applications of AM for CVDs were attempted, including for heart failure, myocardial infarction, pulmonary hypertension, and peripheral artery disease; however, none achieved success. We have developed AM as a therapeutic agent for inflammatory bowel disease in which the vasodilatory effect of AM is minimized. A clinical trial evaluating this AM formulation for acute cerebral infarction is ongoing. We have also developed AM derivatives that exhibit a longer half-life and less vasodilative activity. These AM derivatives can be administered by subcutaneous injection at long-term intervals. Accordingly, these derivatives will reduce the inconvenience in use compared to that for native AM and expand the possible applications of AM for treating CVDs. In this review, we present the latest translational status of AM and its derivatives.
肾上腺髓质素 (AM) 是一种血管舒张肽，具有多种生理功能，包括维持血管张力和内皮屏障功能。在严重炎症（如败血症相关炎症）期间，AM 水平显著升高；因此，AM 有望成为炎症的有用临床标志物和治疗剂。然而，由于心血管疾病 (CVD) 中 AM 水平的升高相对低于感染性疾病，因此 AM 作为 CVD 标志物的价值似乎不那么重要。AM 在血流中的给药途径和半衰期（<30 分钟）限制了 AM 治疗 CVD 的应用。在早期的人类研究中，尝试了 AM 在 CVD 中的各种应用，包括心力衰竭、心肌梗死、肺动脉高压和外周动脉疾病；然而，没有一种方法取得成功。我们已经开发了 AM 作为治疗炎症性肠病的治疗剂，其中 AM 的血管舒张作用最小化。正在进行一项评估这种 AM 制剂治疗急性脑梗死的临床试验。我们还开发了半衰期更长且血管舒张活性更低的 AM 衍生物。这些 AM 衍生物可以通过皮下注射长期间隔给药。因此，与天然 AM 相比，这些衍生物将减少使用上的不便，并扩大 AM 治疗 CVD 的可能应用。在这篇综述中，我们介绍了 AM 及其衍生物的最新转化状态。
