Impaired microvascular reactivity in patients treated with 5-fluorouracil chemotherapy regimens: Potential role of endothelial dysfunction.
Impaired microvascular reactivity in patients treated with 5-fluorouracil chemotherapy regimens: Potential role of endothelial dysfunction.
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接受 5-氟尿嘧啶化疗方案治疗的患者微血管反应性受损：内皮功能障碍的潜在作用。
DOI：
10.1016/j.ijcha.2023.101300
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发表时间：
2023-12
期刊：
影响因子：
--
通讯作者：
Ade CJ
中科院分区：
文献类型：
--
作者：
Hammond ST;Baumfalk DR;Parr SK;Butenas ALE;Scheuermann BC;Turpin VG;Behnke BJ;Hashmi MH;Ade CJ
以5-FU为基础的化疗是否损害微血管内皮功能？这项研究表明，皮肤微血管功能障碍的存在，大概是通过改变eNOS-NO依赖性血管舒张途径，在癌症患者接受5-氟尿嘧啶（5-FU）为基础的化疗方案治疗。图片由Biorender.com创建。5-氟尿嘧啶（5-FU）是第二种最常见的与短期和长期心脏毒性相关的癌症化疗。虽然介导这些毒性的机制尚不清楚，但患者经常出现提示微血管功能障碍的症状。我们检验了接受基于5-FU的化疗方案的癌症治疗的患者会出现微血管反应性受损的假设，并且这些发现将通过5-FU治疗的人冠状动脉内皮细胞（HCAEC）中内皮型一氧化氮合酶（eNOS）基因表达的减少来证实。我们首先对30例接受基于5-FU的癌症化疗（5-FU）的患者和32例年龄、性别、体重指数和既往健康史（不包括癌症）匹配的对照（CON）进行了横断面分析。皮肤微血管反应性进行了评价，通过激光多普勒血流仪响应内皮依赖性（局部皮肤加热，乙酰胆碱离子导入，ACh）和非依赖性（硝普钠离子导入，SNP）的刺激。在体外实验中，在HCAEC中完成，以评估5-FU对eNOS基因表达的影响。与CON相比，eNOS依赖性局部加热后5-FU的微血管反应性降低（P = 0.001）。eNOS抑制剂L-NAME的离子导入未能改变5-FU的加热反应（P = 0.95），尽管CON显著降低（P = 0.03）。5-FU处理组内皮细胞eNOS基因表达明显低于对照组（P < 0.01）。ACh（P = 0.58）和SNP（P = 0.39）的血管舒张峰值在两组之间存在差异。目前的研究结果表明，减少微血管功能沿着eNOS-NO血管舒张通路的癌症患者接受治疗与5-FU为基础的化疗方案，因此，可能提供深入了解5-FU心脏毒性的潜在机制。
Does 5-FU-based chemotherapy impair microvascular endothelial function? This study demonstrates the presence of cutaneous microvascular dysfunction—presumably via alterations in eNOS-NO dependent vasodilatory pathways—in patients undergoing cancer treatment with 5-fluorouracil (5-FU) based chemotherapy regimens. Figure created with Biorender.com. 5-fluorouracil (5-FU) is the second most common cancer chemotherapy associated with short- and long-term cardiotoxicity. Although the mechanisms mediating these toxicities are not well understood, patients often present with symptoms suggestive of microvascular dysfunction. We tested the hypotheses that patients undergoing cancer treatment with 5-FU based chemotherapy regimens would present with impaired microvascular reactivity and that these findings would be substantiated by decrements in endothelial nitric oxide synthase (eNOS) gene expression in 5-FU treated human coronary artery endothelial cells (HCAEC). We first performed a cross-sectional analysis of 30 patients undergoing 5-FU based chemotherapy treatment for cancer (5-FU) and 32 controls (CON) matched for age, sex, body mass index, and prior health history (excluding cancer). Cutaneous microvascular reactivity was evaluated by laser Doppler flowmetry in response to endothelium-dependent (local skin heating; acetylcholine iontophoresis, ACh) and -independent (sodium nitroprusside iontophoresis, SNP) stimuli. In vitro experiments in HCAEC were completed to assess the effects of 5-FU on eNOS gene expression. 5-FU presented with diminished microvascular reactivity following eNOS-dependent local heating compared to CON (P = 0.001). Iontophoresis of the eNOS inhibitor L-NAME failed to alter the heating response in 5-FU (P = 0.95), despite significant reductions in CON (P = 0.03). These findings were corroborated by lower eNOS gene expression in 5-FU treated HCAEC (P < 0.01) compared to control. Peak vasodilation to ACh (P = 0.58) nor SNP (P = 0.39) were different between groups. The present findings suggest diminished microvascular function along the eNOS-NO vasodilatory pathway in patients with cancer undergoing treatment with 5-FU-based chemotherapy regimens and thus, may provide insight into the underlying mechanisms of 5-FU cardiotoxicity.
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DOI：
10.1152/ajpheart.00446.2017
发表时间：
2018-02-01
影响因子：
4.8
作者：
Alba, Billie K.;Greaney, Jody L.;Alexander, Lacy M.
通讯作者：
Alexander, Lacy M.
影响因子：
8.3
作者：
Green, Daniel J.;Dawson, Ellen A.;Thijssen, Dick H. J.
通讯作者：
Thijssen, Dick H. J.
影响因子：
3.3
作者：
Bruning, Rebecca S.;Santhanam, Lakshmi;Holowatz, Lacy A.
通讯作者：
Holowatz, Lacy A.
影响因子：
1.8
作者：
Buechel, Barbara;Rhyn, Peter;Largiader, Carlo R.
通讯作者：
Largiader, Carlo R.
影响因子：
7.3
作者：
Altieri, Paola;Murialdo, Roberto;Spallarossa, Paolo
通讯作者：
Spallarossa, Paolo