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缺血性疾病中的血管生成疗法。

Angiogenesis therapy in ischemic disease.

作者信息

Silvestre J S, Lévy B I

机构信息

INSERM U541, hôpital Lariboisière, institut fédératif de recherche circulation-Paris 7, université Paris 7-Denis Diderot, 75475 Paris.

出版信息

Arch Mal Coeur Vaiss. 2002 Mar;95(3):189-96.

Abstract

The ability of organisms to spontaneously develop collateral vessels represents an important response to vascular occlusive diseases that determines the severity of residual tissue ischemia. Neovascularization of ischemic cardiac or skeletal muscle may be sufficient to preserve tissue integrity and/or function, and may thus be considered to be therapeutic. Innovative gene technologies and advances in animal modeling have enabled research scientists to develop therapeutic angiogenesis strategies applied in animal models of limb or myocardial ischemia and in treatment of patients with peripheral vascular obstruction or coronary artery diseases. Several therapeutic strategies have been proposed and tested even at the clinical level. Recent studies have established the feasibility of using recombinant angiogenic growth factors (mainly VEGF and FGF) to enhance angiogenesis in patients with limb or myocardial ischemia. Angiogenesis therapies using cells as a support for growth factor delivery or using endothelial progenitor cells which may directly participate in the angiogenic process have also been developed. Finally, one potential alternative strategy may be the use of drugs with pro-angiogenic activity, available in an oral formulation and which are currently administered to patients for treatment of different pathologies. All strategies of angiogenesis therapy currently being tested have the potential to be effective in the treatment of ischemic disease. However, such strategies may cause harmful side effects which emphasize the need to be aware of the biological effects of each angiogenic agent proposed for clinical studies.

摘要

生物体自发形成侧支血管的能力是对血管闭塞性疾病的一种重要反应,它决定了残余组织缺血的严重程度。缺血心肌或骨骼肌的新生血管形成可能足以维持组织完整性和/或功能,因此可被视为具有治疗作用。创新的基因技术和动物模型的进展使研究科学家能够开发出应用于肢体或心肌缺血动物模型以及治疗外周血管阻塞或冠状动脉疾病患者的治疗性血管生成策略。甚至在临床层面也已经提出并测试了几种治疗策略。最近的研究证实了使用重组血管生成生长因子(主要是VEGF和FGF)来增强肢体或心肌缺血患者血管生成的可行性。还开发了以细胞作为生长因子递送载体的血管生成疗法,或者使用可能直接参与血管生成过程的内皮祖细胞的疗法。最后,一种潜在的替代策略可能是使用具有促血管生成活性的药物,这些药物有口服制剂,目前已用于治疗不同病症的患者。目前正在测试的所有血管生成治疗策略都有可能有效治疗缺血性疾病。然而,这些策略可能会引起有害的副作用,这凸显了了解每种拟用于临床研究的血管生成剂的生物学效应的必要性。

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