PGF2α-FP Receptor Ameliorates Senescence of VSMCs in Vascular Remodeling by Src/PAI-1 Signal Pathway.
PGF2α-FP Receptor Ameliorates Senescence of VSMCs in Vascular Remodeling by Src/PAI-1 Signal Pathway.
复制标题
PGF2α-FP 受体通过 Src/PAI-1 信号通路改善血管重塑中 VSMC 的衰老
DOI：
10.1155/2022/2908261
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发表时间：
2022
影响因子：
--
通讯作者：
Shang YY
中科院分区：
文献类型：
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作者：
Hu BA;Sai WW;Yuan J;Lan HT;Qi J;Wang D;Zhang W;Wang ZH;Zhong M;Shang YY
血管平滑肌细胞（VSMC）的衰老参与老年小鼠的血管重塑。前列腺素F2α- (PGF2α-) FP 受体在心血管疾病(CVD)、高血压和心脏纤维化中发挥着关键作用。然而，其在衰老引起的动脉硬化中的作用尚未完全阐明。在这项研究中，我们发现衰老小鼠主动脉和衰老 VSMC 中 FP 受体表达增加。 FP受体基因沉默可以改善血管衰老、抑制氧化应激，从而降低PAI-1的表达，抑制MMPs的活化，最终改善ECM的过度沉积，延缓血管纤维化的进程。 FP受体可通过上调Src/PAI-1信号通路促进VSMC衰老，抑制FP受体/Src/PAI-1信号通路可改善VSMC体外衰老，表现为衰老相关蛋白P16、P21、P53和GLB1表达减少。这些结果表明，FP 受体是血管衰老的促进者，通过 Src 和 PAI-1 上调诱导细胞衰老、氧化应激和血管重塑。
Senescence in vascular smooth muscle cells (VSMCs) is involved in vascular remodeling of aged mice. ProstaglandinF2α- (PGF2α-) FP receptor plays a critical role in cardiovascular diseases (CVDs), hypertension, and cardiac fibrosis. However, its role in senescence-induced arteriosclerosis is yet to be fully elucidated. In this study, we found that FP receptor expression increased in aged mouse aortas and senescence VSMCs. FP receptor gene silencing can ameliorate vascular aging and inhibit oxidative stress, thereby reducing the expression of PAI-1, inhibiting the activation of MMPs, and ultimately improving the excessive deposition of ECM and delaying the process of vascular fibrosis. FP receptor could promote VSMC senescence by upregulated Src/PAI-1 signal pathway, and inhibited FP receptor/Src/PAI-1 pathway could ameliorate VSMCs aging in vitro, evidenced by the decrease of senescence-related proteins P16, P21, P53, and GLB1 expressions. These results suggested that FP receptor is a promoter of vascular aging, by inducing cellular aging, oxidative stress, and vascular remodeling via Src and PAI-1 upregulation.