Therapeutic Angiogenesis Using Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor Using Various Delivery Strategies.

Laham, Garcia, Baim, Post, Simons
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Abstract

Therapeutic angiogenesis is a novel technique that may provide a treatment strategy for ischemic heart diseasepatients who are not candidates for standard revascularization procedures. It works by promoting the growth of blood vessels provide new venues for blood flow. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are the most widely studied angiogenic agents. They have been shown to induce functionally significant angiogenesis in various animal models of chronic myocardial ischemia using various delivery strategies. Preclinical and clinical studies using these growth factors are reviewed with an emphasis on the different delivery strategies,including intracoronary and intravenous delivery; left atrial injections; intrapericardial administration; local intravascular and perivascular delivery; and intramyocardial delivery using single bolus delivery, repeated administration, gene therapy, and sustained delivery. Although intracoronary and intravenous delivery may be preferred for their ease of use and their applicability to a large patient population, systemic recirculation and lack of sustained tissue exposure to these therapeutic agents may limit the usefulness of this approach. Intrapericardial and intramyocardial administration, sustained local delivery, and second-generation gene therapy vectors may allow a safer and more sustained administration and may be preferable for clinical use. However, only well-designed randomized, double-blind placebo-controlled trials using outcome measures tailored to myocardial angiogenesis will determine the feasibility and effectiveness of this treatment modality.

使用不同递送策略的碱性成纤维细胞生长因子和血管内皮生长因子治疗血管生成。
治疗性血管生成是一种新技术,可以为不适合标准血运重建手术的缺血性心脏病患者提供治疗策略。它的工作原理是促进血管的生长,为血液流动提供新的场所。碱性成纤维细胞生长因子(bFGF)和血管内皮生长因子(VEGF)是研究最广泛的血管生成因子。在慢性心肌缺血的各种动物模型中,它们已被证明可以通过不同的递送策略诱导功能显著的血管生成。本文回顾了使用这些生长因子的临床前和临床研究,重点介绍了不同的给药策略,包括冠状动脉内和静脉内给药;左心房注射;intrapericardial管理;局部血管内和血管周围分娩;心内给药采用单丸给药、重复给药、基因治疗和持续给药。虽然冠状动脉内和静脉内给药可能因其易于使用和适用于大量患者而成为首选,但全身再循环和缺乏持续的组织暴露于这些治疗药物可能限制了这种方法的有效性。心包内和心包内给药、持续局部给药和第二代基因治疗载体可能使给药更安全、更持久,可能更适合临床使用。然而,只有经过精心设计的随机、双盲安慰剂对照试验才能确定这种治疗方式的可行性和有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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