Soluble receptor for advanced glycation end-products promotes angiogenesis through activation of STAT3 in myocardial ischemia/reperfusion injury
Soluble receptor for advanced glycation end-products promotes angiogenesis through activation of STAT3 in myocardial ischemia/reperfusion injury
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晚期糖基化终末产物的可溶性受体通过激活心肌缺血/再灌注损伤中的 STAT3 促进血管生成
DOI：
10.1007/s10495-020-01602-8
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发表时间：
2020-04-24
期刊：
影响因子：
7.2
通讯作者：
Guo, Caixia
中科院分区：
文献类型：
--
作者：
Cao, Xianxian;Li, Bin;Guo, Caixia
晚期糖基化终产物可溶性受体（soluble receptor for advanced glycation end-products，sCRP）通过抑制缺血/再灌注（I/R）损伤期间的心肌细胞凋亡和自噬而发挥心脏保护作用，还已知其在缺血后再灌注损伤-关键肢体缺血（post-ischemic reperfusion injury-critical limb ischemia，PIRI-CLI）小鼠中增强血管生成。然而，sodium是否通过促进血管生成来保护心脏免受心肌I/R损伤仍不清楚。结扎C57 BL/6小鼠左前降支（LAD）30 min，再灌注2周，建立心肌I/R损伤模型。心肌微血管内皮细胞（CMECs）的I/R损伤通过氧和糖剥夺来复制。结果表明，丹参可逆转I/R引起的心功能不全、炎症反应和心肌纤维化。CD31免疫组化染色显示，丹参可增加I/R损伤后血管密度。体外培养的CMECs实验结果表明，丹参可抑制缺血再灌注后细胞凋亡，促进细胞增殖、迁移和血管生成。这些作用依赖于信号转导子和转录激活子3（STAT3）通路。总之，本研究表明，STAT3的激活有助于通过促进血管生成来保护心肌I/R损伤。
Soluble receptor for advanced glycation end-products (sRAGE), which exerts cardioprotective effect through inhibiting cardiomyocyte apoptosis and autophagy during ischemia/reperfusion (I/R) injury, is also known to enhance angiogenesis in post-ischemic reperfusion injury-critical limb ischemia (PIRI-CLI) mice. However, whether sRAGE protects the heart from myocardial I/R injury via promoting angiogenesis remains unclear. Myocardial model of I/R injury was conducted by left anterior descending (LAD) ligation for 30 min and reperfusion for 2 weeks in C57BL/6 mice. And I/R injury in cardiac microvascular endothelial cells (CMECs) was duplicated by oxygen and glucose deprivation. The results showed that I/R-induced cardiac dysfunction, inflammation and myocardial fibrosis were all reversed by sRAGE. CD31 immunohistochemistry staining showed that sRAGE increased the density of vessels after I/R injury. The results from cultured CMECs showed that sRAGE inhibited apoptosis and increased proliferation, migration, angiogenesis after exposure to I/R. These effects were dependent on signal transducer and activator of transcription 3 (STAT3) pathway. Together, the present study demonstrated that activation of STAT3 contributed to the protective effects of sRAGE on myocardial I/R injury via promoting angiogenesis.