Lymphatic Vasculature and Inflammation Research Laboratory, Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Talca, Chile.
Lymphat Res Biol. 2020 Apr;18(2):136-145. doi: 10.1089/lrb.2019.0008. Epub 2019 Aug 20.
Early lymphedema detection may reduce the symptoms and improve clinical outcomes. However, the lack of reliable serum biomarkers capable of predicting lymphedema development is a current medical problem. In this study, we investigated if serum levels of hyaluronic acid (HA) and leukotriene B4 (LTB4), two molecules involved in lymphedema development, may work as predictors of this condition. A mouse model of acquired lymphedema was generated through ablation of tail dermal lymphatic network. Tail diameter was measured daily, and HA and LTB4 serum levels were analyzed before and during the development of lymphedema. We found increased serum levels of HA and reduced levels of LTB4 at early days before the appearance of lymphedema signs. Similar results were observed in the lymphedema tissue. Increased local and systemic inflammation was also detected at early time points. Moreover, the ratio LTB4/HA arises as the strongest predictor for lymphedema development. In fact, we found an inverse correlation in our model, where reduced LTB4/HA levels showed increased lymphedema signs. These findings suggest that serum ratio of LTB4/HA may be a useful biomarker to predict acquired lymphedema development, with potential to be used in clinical conditions such as breast cancer patients.
早期淋巴水肿的检测可以减轻症状并改善临床结果。然而，目前缺乏能够预测淋巴水肿发展的可靠血清生物标志物，这是一个医学难题。在这项研究中，我们研究了血清中透明质酸（HA）和白三烯 B4（LTB4）的水平是否可以作为淋巴水肿的预测因子，这两种分子都参与了淋巴水肿的发展。通过切除尾部皮肤淋巴管建立获得性淋巴水肿的小鼠模型。每天测量尾部直径，并在淋巴水肿发生之前和发展过程中分析血清中 HA 和 LTB4 的水平。我们发现，在出现淋巴水肿迹象之前的早期，HA 的血清水平升高，而 LTB4 的水平降低。在淋巴水肿组织中也观察到了类似的结果。早期还检测到局部和全身炎症增加。此外，LTB4/HA 的比值是淋巴水肿发展的最强预测因子。事实上，我们在模型中发现了一个相反的相关性，即 LTB4/HA 水平降低与淋巴水肿迹象增加有关。这些发现表明，血清 LTB4/HA 比值可能是预测获得性淋巴水肿发展的有用生物标志物，有望在乳腺癌等临床情况下得到应用。
