UNASSIGNED: We use SVAS here as a model of vascular proliferative disease using both human induced pluripotent stem cell-derived vascular smooth muscle cells and developmental Eln+/- mouse models to establish de novo elastin assembly as a new therapeutic intervention.
UNASSIGNED: We demonstrate mitigation of vascular proliferative abnormalities following de novo extracellular elastin assembly through the addition of the polyphenol epigallocatechin gallate to SVAS human induced pluripotent stem cell-derived vascular smooth muscle cells and in utero to Eln+/- mice.
UNASSIGNED: We demonstrate de novo elastin deposition normalizes SVAS human induced pluripotent stem cell-derived vascular smooth muscle cell hyperproliferation and rescues hypertension and aortic mechanics in Eln+/- mice, providing critical preclinical findings for the future application of epigallocatechin gallate treatment in humans.
■我们在这里使用SVAS作为血管增殖性疾病的模型,使用人类诱导的多能干细胞衍生的血管平滑肌细胞和发育的Eln±小鼠模型来建立从头弹性蛋白组装作为新的治疗干预。
■我们证明了通过向SVAS人诱导的多能干细胞衍生的血管平滑肌细胞中添加多酚表没食子儿茶素没食子酸酯并在子宫内添加到Eln±小鼠,可以减轻从头细胞外弹性蛋白组装后的血管增殖异常。
■我们证明了从头弹性蛋白沉积使SVAS人诱导的多能干细胞衍生的血管平滑肌细胞过度增殖正常化,并挽救了Eln±小鼠的高血压和主动脉力学,为表没食子儿茶素没食子酸酯在人类治疗中的未来应用提供关键的临床前发现。