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[动脉生成治疗性刺激的机制与潜力]

[Mechanisms and potential of the therapeutic stimulation of arteriogenesis].

作者信息

Schirmer S H, van Royen N, Laufs U, Böhm M

机构信息

Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar.

出版信息

Dtsch Med Wochenschr. 2009 Feb;134(7):302-6. doi: 10.1055/s-0028-1123996. Epub 2009 Feb 5.

Abstract

The stimulation of collateral artery growth (arteriogenesis) is a promising alternative approach to non-invasively treat arterial obstructive disease, such as coronary, peripheral or cerebral artery disease. Patients unable to undergo conventional revascularization strategies may benefit from adaptive arteriogenesis. Underlying mechanisms are experimentally validated and include an increase in shear stress after obstruction or occlusion of a major artery; monocyte adhesion, transmigration and perivascular accumulation, secretion of growth factors; and smooth muscle and endothelial cell proliferation and growth of pre-existent collateral arteries. Therapeutic stimulation of arteriogenesis with cytokines has been successfully performed in experimental models. Translation into clinical practice, however, has hitherto been problematic. Reasons for this include differences between the healthy laboratory animal and an often severely diseased patient, possible harmful effects of pro-arteriogenic therapies and unsuitable clinical endpoints for the detection of collateral artery growth. Recent investigations of human arteriogenesis demonstrate significant inter-individual differences and point towards the importance of anti-arteriogenic mechanisms in patients with impaired adaptive arteriogenesis and high cardiovascular risk factors.

摘要

刺激侧支动脉生长(动脉生成)是一种有前景的非侵入性治疗动脉阻塞性疾病的替代方法,如冠状动脉疾病、外周动脉疾病或脑动脉疾病。无法接受传统血管重建策略的患者可能会从适应性动脉生成中获益。其潜在机制已在实验中得到验证,包括主要动脉阻塞或闭塞后剪切应力增加;单核细胞黏附、迁移和血管周围聚集、生长因子分泌;以及平滑肌和内皮细胞增殖以及已有侧支动脉的生长。在实验模型中,用细胞因子对动脉生成进行治疗性刺激已成功实施。然而,将其转化为临床实践迄今仍存在问题。原因包括健康实验动物与通常病情严重的患者之间的差异、促动脉生成疗法可能产生的有害影响以及检测侧支动脉生长的不合适临床终点。最近对人类动脉生成的研究表明个体间存在显著差异,并指出在适应性动脉生成受损且有高心血管危险因素的患者中,抗动脉生成机制的重要性。

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