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确定对内皮细胞功能障碍和高血压的缓解策略,以应对VEGF受体抑制剂
Nicholas D Camarda1,2, Qing Lu1, Dawn M Meola3
1Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, U.S.A.
Clinical science (London, England : 1979)
|September 16, 2024
概括
血管内皮生长因子受体抑制剂 (VEGFRis) 通过内皮细胞 (EC) 功能障碍引起高血压. 像多克萨佐辛这样的α阻断剂保护ECs,而利西诺普里尔直接针对高血压,为管理癌症治疗副作用提供了双重策略.
科学领域:
- 心脏瘤学是一门专业.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 血管内皮生长因子受体抑制剂 (VEGFRis) 改善癌症存活率,但诱导高血压,与内皮细胞 (EC) 功能障碍有关.
- 目前对VEGFRi诱导的高血压的治疗策略有限.
研究的目的:
- 为了确定减轻VEGFRi诱导的EC功能障碍的药物.
- 在临床前模型和狗癌症患者中评估已识别的药物的疗效.
主要方法:
- 用VEGFRi处理的ECs的基蛋白质分析,以选保护性药物.
- 在初级大动脉EC,小鼠和狗癌症患者中的验证.
- 在犬癌患者的随机临床试验中,比较了多克萨佐辛和利西诺普里尔.
主要成果:
- 在小鼠和狗中,VEGFRi治疗增加了血压,并导致内皮和功能障碍.
- 阿尔法上腺抗剂,特别是多克萨佐辛,被确定为EC功能障碍的强效缓解剂.
- 多克萨索辛保护了ECs,但并没有完全消除小鼠的高血压;利西诺普里尔降低了血压,但没有影响ECs.
- 多克萨佐辛和利西诺普里尔都有效地降低了缩血压在犬癌患者.
结论:
- 仅仅逆转EC功能障碍是不足以完全缓解VEGFRi诱导的高血压.
- 多克萨佐辛和利西诺普里尔是VEGFRi诱导的高血压的安全有效的抗高血压药.
- 蛋白组学是识别心脏瘤学保护剂的宝贵工具.
- 狗模型为加速临床发展提供了一个翻译平台.
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