School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Biochem Biophys Res Commun. 2024 Nov 26;735:150838. doi: 10.1016/j.bbrc.2024.150838. Epub 2024 Oct 15.
Venous malformation (VM) is a prevalent congenital vascular anomaly characterized by abnormal blood vessel growth, leading to disfigurement and dysfunction. Sclerotherapy, a minimally invasive approach, has become a primary therapeutic modality for VM, but its efficacy is hampered by the rapid dilution and potential adverse effects. In this study, we introduced a series of cationic amphiphilic molecules, fatty alcohol esters (TA6, TA8, and TA9) of tranexamic acid (TA), which self-assembled into low-molecular-weight gels (LMWGs) in water. The TA9, in particular, is released slowly when hydrogel is injected into the vein locally. Then, it damages the venous wall by destroying cell membranes and precipitating proteins, causing inflammation and thrombosis, thickening of the venous wall, effectively inducing irreversible vein fibrosis. Additionally, TA9 can be rapidly degraded into TA in plasma to reduce toxicity caused by diffusion. Overall, this study suggests that the cationic amphiphilic molecule TA9 is a promising sclerosant for VM treatment, offering a novel, effective, and safe therapeutic option with potential for clinical translation.
静脉畸形（VM）是一种常见的先天性血管畸形，其特征是血管异常生长，导致畸形和功能障碍。硬化疗法是一种微创方法，已成为 VM 的主要治疗方式，但由于其快速稀释和潜在的不良反应，其疗效受到限制。在这项研究中，我们引入了一系列阳离子两亲分子，即氨甲环酸（TA）的脂肪醇酯（TA6、TA8 和 TA9），它们在水中自组装成低分子量凝胶（LMWG）。特别是 TA9，当局部注射到静脉中的水凝胶时，它会缓慢释放。然后，它通过破坏细胞膜和沉淀蛋白质来损伤静脉壁，引起炎症和血栓形成，使静脉壁变厚，有效地诱导不可逆的静脉纤维化。此外，TA9 可以在血浆中迅速降解为 TA，以减少扩散引起的毒性。总的来说，这项研究表明，阳离子两亲分子 TA9 是一种很有前途的 VM 治疗硬化剂，为临床转化提供了一种新颖、有效和安全的治疗选择。
