Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
Int J Mol Med. 2011 Aug;28(2):207-13. doi: 10.3892/ijmm.2011.671. Epub 2011 Apr 13.
In addition to excessive proliferation, reduced apoptosis of vascular smooth muscle cells (VSMCs) plays a key role in aging-exaggerated neointima formation after vascular injury. Our previous studies have shown that impaired expression of Jagged1 in the endothelium may be a key event that leads to enhanced VSMC proliferation in the elderly. Here, we are the first to investigate whether the expression of Jagged1 in endothelial cells (ECs) may regulate apoptosis of VSMCs. We discovered that VSMCs co-cultured with senescent ECs exhibited decreased susceptibility to H₂O₂-induced apoptosis compared with those co-cultured with young ECs. Senescent ECs also displayed lower Jagged1 expression compared to young ECs, which was more evident after H₂O₂ stimulation. Overexpression of Jagged1 in senescent ECs significantly promoted H₂O₂-induced apoptosis in the co-cultured VSMCs, whereas silencing Jagged1 expression in young ECs reduced H2O2-induced apoptosis in the co-cultured VSMCs. Our studies also revealed that Jagged1 expressed in ECs exerted its pro-apoptotic activity by lowering expression of the anti-apoptotic protein Bcl-2. These results demonstrate that aging reduces the susceptibility of co-cultured VSMCs to H₂O₂-induced apoptosis through impaired Jagged1 expression in ECs.
除了过度增殖，血管平滑肌细胞（VSMCs）的凋亡减少在血管损伤后加速老化的新生内膜形成中也起着关键作用。我们之前的研究表明，内皮细胞中 Jagged1 的表达受损可能是导致老年人 VSMC 增殖增强的关键事件。在这里，我们首次研究了内皮细胞（ECs）中 Jagged1 的表达是否可能调节 VSMC 的凋亡。我们发现，与与年轻 ECs 共培养的 VSMCs 相比，与衰老 ECs 共培养的 VSMCs 对 H₂O₂诱导的凋亡的敏感性降低。与年轻 ECs 相比，衰老 ECs 中的 Jagged1 表达也较低，在 H₂O₂刺激后更为明显。在衰老的 ECs 中转染 Jagged1 过表达显著促进了共培养的 VSMCs 中 H₂O₂诱导的凋亡，而在年轻的 ECs 中沉默 Jagged1 表达则降低了共培养的 VSMCs 中 H2O2 诱导的凋亡。我们的研究还表明，ECs 中表达的 Jagged1 通过降低抗凋亡蛋白 Bcl-2 的表达发挥其促凋亡活性。这些结果表明，衰老通过降低 ECs 中 Jagged1 的表达，降低了共培养的 VSMCs 对 H₂O₂诱导的凋亡的敏感性。
