Abstract
The aim of the present study was to investigate the levels of vascular endothelial growth factor (VEGF)-antagonizing cytokines and VEGF-influenced vascular stabilizing cytokines in patients with moyamoya disease (MMD) and the association with postoperative collateral vessel formation. The study population included 53 MMD patients that had undergone indirect bypass surgery and 50 healthy controls. Serum levels of VEGF, thrombospondin-1 (TSP-1), TSP-2, soluble VEGF receptor-1 (sVEGFR-1), sVEGFR-2, endostatin, angiopoietin-1 (Ang-1) and Ang-2 were measured at the baseline (preoperative) and at day seven following surgery. Postoperative collateralization assessment was conducted upon the six-month follow-up cerebral angiography. Cytokine levels were compared between patients with good or poor collateral formation. Compared with the healthy controls, MMD patients exhibited lower baseline levels of sVEGFR-1 (P<0.0001) and sVEGFR-2 (P<0.0001), but higher VEGF expression (P<0.0001). Ang-1 and Ang-2 levels did not exhibit any difference between the two groups. On day seven following surgery, MMD patients exhibited an almost unchanged sVEGFR-1 and sVEGFR-2 expression level, but upregulated expression of VEGF (P<0.0001), Ang-1 (P<0.0001) and TSP-2 (P<0.0001). The six-month follow-up angiographies revealed that 21 patients (45.65%) that had undergone the same surgical procedure achieved good collateralization. Patients with good collateral formation appeared to have lower sVEGFR-1 and sVEGFR-2 levels prior to (P=0.029 and P=0.045, respectively) and at day seven (P=0.044 and P=0.047, respectively) following bypass surgery when compared with the patients with worse collateralization. Therefore, sVEGFR-1 and sVEGFR-2 may play a role in the pathogenesis of MMD. Lower levels of sVEGFR-1 and sVEGFR-2 indicated better postoperative collateralization in the six months following indirect bypass surgery. However, Ang-1 and Ang-2 may not be specifically involved in the course of MMD.
Highlights
Moyamoya disease (MMD) is a progressive cerebrovascular disease that is characterized by the formation of excessive collateral vessels at the brain base and occlusive or stenotic changes of the main cerebral arteries [1]
Vascular endothelial growth factor (VEGF) contributes to the course of arteriogenesis, which is the enlargement of preexisting arterioles, triggered by increased fluid shear stress [7]
A recent genetic study revealed that among several VEGF gene polymorphisms, the CC genotype of VEGF‐634 may be associated with better collateral vessel formation in MMD following surgery [11]
Summary
Moyamoya disease (MMD) is a progressive cerebrovascular disease that is characterized by the formation of excessive collateral vessels (moyamoya vessels) at the brain base and occlusive or stenotic changes of the main cerebral arteries [1]. Collateral formation plays a key role in the pathogenesis of MMD [4]. The surgical treatments for MMD predominantly aim at developing collateral vessels feeding from the external carotid artery system [5]. Vascular endothelial growth factor (VEGF) is a fundamental angiogenic factor in collateral vessel formation. Abundant VEGF does not appear to result in sufficient and persistent collateral formation in MMD. A recent genetic study revealed that among several VEGF gene polymorphisms, the CC genotype of VEGF‐634 may be associated with better collateral vessel formation in MMD following surgery [11]. In addition to angiogenic factors, such as VEGF, vessel formation is regulated by antiangiogenic cytokines and vascular stabilizing factors.
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