Abstract
Aneurysm (AN) embolization is an important treatment for cerebral aneurysms. The endothelialization of the aneurysm neck is crucial for preventing aneurysm recurrence. Sitagliptin is a therapeutic drug for diabetes that has been reported to have cardiovascular-protective effects. This study investigated the effect of sitagliptin on endothelial progenitor cell (EPC) function and endothelialization of aneurysm necks after embolization. The effect of sitagliptin on aneurysm neck endothelialization was examined using a rat aneurysm embolization model. We isolated EPCs and used CCK-8 (Cell Counting Kit-8) and annexin V/PI to analyze the effect of sitagliptin on the proliferation and apoptosis of EPCs. The effects of sitagliptin on the migration and invasion of EPCs were examined using scratch and Transwell assays. The effect of sitagliptin on the angiogenic ability of EPCs was examined using a sprouting assay. Western blot analysis and ELISA were used to analyze the effect of sitagliptin on the expression of proangiogenic factors in EPCs. The in vivo results indicated that sitagliptin promoted endothelialization of the aneurysm neck and increased circulating EPCs and expression levels of SDF-1 and VEGF in peripheral blood. Sitagliptin promoted the proliferation, migration, invasion, and angiogenic abilities of EPCs. Western blot analysis and ELISA showed that sitagliptin promoted the expression of SDF-1 and VEGF in progenitor endothelial cells. Western blot assays showed that sitagliptin activated the expression of NRF2, which is dependent on the function of CXCR4. Furthermore, sitagliptin promoted progenitor endothelial cell migration, invasion and angiogenesis through the SDF-1/CXCR4/NRF2 signaling pathway. Additionally, progenitor endothelial cells expressed SDF-1 and VEGF. The promotion of endothelialization by sitagliptin provides an additional therapeutic option for preventing the recurrence of AN.
Highlights
Intracranial aneurysms (IAs) are one of the main causes of subarachnoid hemorrhage due to the abnormal expansion of the arterial wall and occur due to various reasons [1]
endothelial progenitor cell (EPC) to Induce Endothelialization in the According to previous studies, sitagliptin increases circulating levels of SDF-1, which has an important role in inducing endothelialization in aneurysm necks [21], and so we investigated the role of sitagliptin in endothelialization and mobilization of EPCs
The results showed that sitagliptin significantly increased the number of EPCs in the peripheral blood, while AMD3100 significantly decreased the level of EPCs and VEGF in the peripheral blood (Figures 1A–E)
Summary
Intracranial aneurysms (IAs) are one of the main causes of subarachnoid hemorrhage due to the abnormal expansion of the arterial wall and occur due to various reasons [1]. Subarachnoid hemorrhage caused by rupture of aneurysms occurs suddenly and severely, which is an important cause of human death. The long-term recurrence rate is as high as 24% [5], and so preventing the long-term recurrence of cerebral aneurysms after embolization is the most noteworthy issue in interventional therapy. An increasing number of studies have focused on the process of endothelialization of the aneurysmal neck after embolization, which prevents the recurrence of cerebral aneurysms to a certain extent [5]. Incomplete endothelialization of intracranial aneurysms increases the risk of recurrence [6]. Promoting the degree of endothelialization of intracranial aneurysms could help improve the prognosis of patients
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