Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation
Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation
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DOI：
10.1093/annonc/mdm550
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发表时间：
2008-05-01
影响因子：
50.5
通讯作者：
Levy, B. I.
中科院分区：
文献类型：
--
作者：
Mourad, J. -J.;des Guetz, G.;Levy, B. I.
在所有涉及贝伐单抗（一种旨在靶向血管内皮生长因子（VEGF）的抗血管生成剂）的研究中均报告了动脉高血压（HT）。贝伐珠单抗相关HT的潜在机制尚未明确。至于内皮功能障碍和微血管稀疏的标志，在所有形式的HT，我们测试的假设，抗VEGF治疗可以改变微循环在非肿瘤组织，从而导致血压（BP）的增加，我们使用活体视频显微镜来测量真皮毛细血管密度的手指背。采用激光多普勒血流仪结合匹鲁卡品（乙酰胆碱类似物）离子导入评价微血管内皮功能。所有测量均在18名患者接受贝伐单抗治疗6个月前后进行（平均累积剂量：与基线相比，治疗6个月后平均BP增加，收缩压和舒张压从129 +/- 13/75 +/- 7 mmHg增加到145 +/- 17/82 +/- 7 mmHg，P < 0.0001。与基线相比，6个月时的平均真皮毛细血管密度显著降低（75 +/- 12对83 +/- 13/mm（2）; P < 0.0001），以及匹鲁卡品诱导的血管舒张贝伐单抗治疗组内皮功能受损，毛细血管稀疏;这两种变化是密切相关的，并且可能是大多数患者中观察到的BP升高的原因。
Arterial hypertension (HT) has been reported in all studies involving bevacizumab, an antiangiogenic agent designed to target vascular endothelial growth factor (VEGF). The mechanism underlying bevacizumab-related HT is not yet clearly understood. As far as endothelial dysfunction and microvascular rarefaction are hallmarks in all forms of HT, we tested the hypothesis that anti-VEGF therapy could alter the microcirculation in nontumor tissues and, thus, result in an increase in blood pressure (BP).We used intravital video microscopy to measure dermal capillary densities in the dorsum of the fingers. Microvascular endothelial function was assessed by laser Doppler flowmetry combined with iontophoresis of pilocarpine (acetylcholine analogue). All measurements were carried out in 18 patients before and after a 6-month treatment with bevacizumab (mean cumulative dose: 3.16 +/- 0.90 g).Mean BP was increased after 6 months of therapy compared with baseline, from 129 +/- 13/75 +/- 7 mmHg to 145 +/- 17/82 +/- 7 mmHg for systolic BP and diastolic BP, respectively (P < 0.0001). Compared with the baseline, mean dermal capillary density at 6 months was significantly lower (75 +/- 12 versus 83 +/- 13/mm(2); P < 0.0001), as well as pilocarpine-induced vasodilation ( P < 0.05).Thus, bevacizumab treatment resulted in endothelial dysfunction and capillary rarefaction; both changes are closely associated and could be responsible for the rise in BP observed in most patients.