Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Sci Rep. 2021 Feb 3;11(1):2899. doi: 10.1038/s41598-021-82568-8.
Vascular endothelial growth factor-A (VEGF-A) is assumed to play a crucial role in the development and rupture of vulnerable plaques in the atherosclerotic process. We used a VEGF-A targeted fluorescent antibody (bevacizumab-IRDye800CW [bevacizumab-800CW]) to image and visualize the distribution of VEGF-A in (non-)culprit carotid plaques ex vivo. Freshly endarterectomized human plaques (n = 15) were incubated in bevacizumab-800CW ex vivo. Subsequent NIRF imaging showed a more intense fluorescent signal in the culprit plaques (n = 11) than in the non-culprit plaques (n = 3). A plaque received from an asymptomatic patient showed pathologic features similar to the culprit plaques. Cross-correlation with VEGF-A immunohistochemistry showed co-localization of VEGF-A over-expression in 91% of the fluorescent culprit plaques, while no VEGF-A expression was found in the non-culprit plaques (p < 0.0001). VEGF-A expression was co-localized with CD34, a marker for angiogenesis (p < 0.001). Ex vivo near-infrared fluorescence (NIRF) imaging by incubation with bevacizumab-800CW shows promise for visualizing VEGF-A overexpression in culprit atherosclerotic plaques in vivo.
血管内皮生长因子 A（VEGF-A）被认为在动脉粥样硬化过程中易损斑块的形成和破裂中起关键作用。我们使用一种靶向 VEGF-A 的荧光抗体（贝伐单抗-IRDye800CW [bevacizumab-800CW]）来对（非）罪犯颈动脉斑块进行体内成像和可视化 VEGF-A 的分布。将新鲜的颈动脉内膜切除术切除的人斑块（n = 15）在体外孵育 bevacizumab-800CW。随后的近红外荧光（NIRF）成像显示在罪犯斑块（n = 11）中的荧光信号比非罪犯斑块（n = 3）更强。从无症状患者中获得的斑块显示出与罪犯斑块相似的病理特征。与 VEGF-A 免疫组化的交叉相关显示，91%的荧光罪犯斑块中存在 VEGF-A 过表达的共定位，而在非罪犯斑块中则未发现 VEGF-A 表达（p < 0.0001）。VEGF-A 表达与 CD34 共定位，CD34 是血管生成的标志物（p < 0.001）。用 bevacizumab-800CW 孵育的体外近红外荧光（NIRF）成像显示出在体内可视化罪犯动脉粥样硬化斑块中 VEGF-A 过表达的潜力。
