PAM Theragnostics GmbH, 16761, Hennigsdorf, Germany.
Sci Rep. 2024 Nov 15;14(1):28091. doi: 10.1038/s41598-024-79542-5.
Adrenomedullin (ADM) is a multifaceted peptide hormone involved in numerous physiological processes, including vascular stability, vasodilation, angiogenesis, and anti-inflammatory responses. The processing of ADM results in several fragments, including midregional proadrenomedullin (MR-proADM), and glycine-extended ADM (ADM-Gly) and bioactive ADM (bio-ADM). MR-proADM, the stable ADM fragment, and bio-ADM, the active form of ADM with a short half-life, have been shown to be potent biomarkers in a variety of pathologies. ADM-Gly, the direct precursor of bio-ADM, is a predominant form in human plasma, but remains less understood and least investigated. This study presents the development of a specific immunoluminometric assay for the quantification of ADM-Gly and offers a robust one-step approach for large-scale sample screening. Applied to human and rodent plasma, it elucidates the release kinetics and plasma half-life of ADM-Gly. Our findings confirm the predominance of ADM-Gly in healthy individuals and its significant release under pathological conditions. Our immunoluminometric assay enables precise measurement of ADM-Gly, advancing research into ADM-related pathophysiology and supporting its use as a biomarker and therapeutic target in various diseases.
肾上腺髓质素（ADM）是一种多功能肽激素，参与许多生理过程，包括血管稳定性、血管舒张、血管生成和抗炎反应。ADM 的加工产生几种片段，包括中区域原肾上腺髓质素（MR-proADM）、甘氨酸延伸 ADM（ADM-Gly）和生物活性 ADM（bio-ADM）。MR-proADM 是 ADM 的稳定片段，bio-ADM 是 ADM 的活性形式，半衰期短，已被证明是多种病理情况下的有效生物标志物。ADM-Gly 是 bio-ADM 的直接前体，是人类血浆中的主要形式，但了解较少，研究最少。本研究开发了一种用于定量测定 ADM-Gly 的特异性免疫发光分析方法，并提供了一种用于大规模样品筛选的稳健一步法。应用于人及啮齿动物血浆，阐明了 ADM-Gly 的释放动力学和血浆半衰期。我们的研究结果证实了 ADM-Gly 在健康个体中的优势及其在病理条件下的显著释放。我们的免疫发光分析方法能够精确测量 ADM-Gly，为 ADM 相关病理生理学的研究提供支持，并支持其作为各种疾病的生物标志物和治疗靶点的应用。
