Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder caused by a point mutation in the Lamin A gene that produces the protein progerin. Progerin toxicity leads to accelerated aging and death from cardiovascular disease. To elucidate the effects of progerin on endothelial cells, we prepared tissue-engineered blood vessels (viTEBVs) using induced pluripotent stem cell-derived smooth muscle cells (viSMCs) and endothelial cells (viECs) from HGPS patients. HGPS viECs aligned with flow but exhibited reduced flow-responsive gene expression and altered NOS3 levels. Relative to viTEBVs with healthy cells, HGPS viTEBVs showed reduced function and exhibited markers of cardiovascular disease associated with endothelium. HGPS viTEBVs exhibited a reduction in both vasoconstriction and vasodilation. Preparing viTEBVs with HGPS viECs and healthy viSMCs only reduced vasodilation. Furthermore, HGPS viECs produced VCAM1 and E-selectin protein in TEBVs with healthy or HGPS viSMCs. In summary, the viTEBV model has identified a role of the endothelium in HGPS.

哈钦森-吉尔福德早衰综合症 (HGPS) 是一种罕见疾病，由产生早衰蛋白的核纤层蛋白 A 基因点突变引起。早老素的毒性会导致加速衰老和心血管疾病导致的死亡。为了阐明早老素对内皮细胞的影响，我们使用来自 HGPS 患者的诱导多能干细胞来源的平滑肌细胞 (viSMC) 和内皮细胞 (viEC) 制备了组织工程血管 (viTEBV)。 HGPS viEC 与流量一致，但表现出流量响应基因表达减少和NOS3水平改变。相对于具有健康细胞的 viTEBV，HGPS viTEBV 表现出功能降低，并表现出与内皮相关的心血管疾病标志物。 HGPS viTEBV 表现出血管收缩和血管舒张的减少。用 HGPS viEC 和健康 viSMC 制备 viTEBV 只会减少血管舒张。此外，HGPS viECs 在健康或 HGPS viSMCs 的 TEBV 中产生 VCAM1 和 E-选择素蛋白。总之，viTEBV 模型已经确定了内皮细胞在 HGPS 中的作用。