Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; Jagiellonian University, Doctoral School of Exact and Natural Sciences, Kraków, Poland.
Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
Biochem Biophys Res Commun. 2024 Nov 12;733:150441. doi: 10.1016/j.bbrc.2024.150441. Epub 2024 Jul 23.
Pathological conditions such as oxidative stress or inflammation may alter the homeostasis of adventitia triggering vascular wall remodeling and abnormal angiogenesis, what can lead to development of atherosclerosis. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and metabolic regulator, but its role in angiogenesis is not yet fully defined. Here we utilized an organ-on-a-chip technology to analyze endothelial sprouting in an adventitia-resembling microenvironment. We analyzed angiogenic responses to growth factor gradient across the extracellular matrix-resembling fibrin gel and in cell co-culture in response to GDF-15-treated adventitial fibroblasts. We observed that GDF-15 enhanced the pro-angiogenic effect of vascular endothelial growth factor. On the other hand, GDF-15-treated adventitial fibroblasts decreased endothelial sprouting. GDF-15 seems to indirectly affect endothelial cells and, depending on the microenvironment, its effect can be either pro- or anti-angiogenic.
病理条件，如氧化应激或炎症，可能会改变血管外膜的内稳态，引发血管壁重构和异常血管生成，从而导致动脉粥样硬化的发生。生长分化因子 15（GDF-15）是一种应激反应细胞因子和代谢调节剂，但它在血管生成中的作用尚未完全确定。在这里，我们利用器官芯片技术在类似于外膜的微环境中分析内皮细胞的发芽。我们分析了在细胞共培养中，细胞外基质样纤维蛋白凝胶中生长因子梯度以及对 GDF-15 处理的外膜成纤维细胞的反应，研究了血管生成反应。我们观察到 GDF-15 增强了血管内皮生长因子的促血管生成作用。另一方面，GDF-15 处理的外膜成纤维细胞减少了内皮细胞的发芽。GDF-15 似乎会间接影响内皮细胞，并且根据微环境的不同，其作用可能是促血管生成或抗血管生成。
