A Novel Preclinical Model of Peripheral Artery Disease in Swine for Investigating Flow-Induced Angiogenesis.

IF 2.3 4区医学 Q3 PERIPHERAL VASCULAR DISEASE

Journal of Vascular Research Pub Date : 2025-01-01 Epub Date: 2025-08-07 DOI:10.1159/000547455

Grzegorz Jodlowski, May Dvir, Colin Price, Amy Benike, Joanna Jaroch, Jonathan J Morrison

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引用次数: 0

Abstract

Introduction: Peripheral artery disease (PAD) affects over 200 million people globally and remains a therapeutic challenge, particularly in patients who are not candidates for standard revascularization. While shear stress-induced angiogenesis holds promise as a novel therapeutic strategy, translational platforms to evaluate its efficacy are lacking.

Methods: We developed a large-animal model of PAD using familial hypercholesterolemic miniature swine fed an atherogenic diet to induce metabolic syndrome. Hindlimb ischemia was surgically induced by excising the right external iliac artery with collateral ligation. After a 3-4 week ischemic phase, targeted retrograde perfusion was delivered via a miniaturized extracorporeal centrifugal pump to generate sustained flow-mediated shear stress. Functional, imaging, and molecular endpoints were assessed throughout the protocol.

Conclusion: This reproducible swine model offers a metabolically relevant platform for investigating perfusion-driven angiogenesis and evaluating novel flow-based revascularization therapies for PAD. It addresses a critical translational gap in preclinical vascular research.

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一种用于研究血流诱导血管生成的猪外周动脉疾病的新型临床前模型。

外周动脉疾病（PAD）影响全球超过2亿人，仍然是一个治疗挑战，特别是对于那些不适合标准血运重建术的患者。虽然剪切应力诱导的血管生成有望作为一种新的治疗策略，但缺乏评估其疗效的翻译平台。方法：采用家族性高胆固醇血症的小型猪饲喂致动脉粥样硬化饮食诱导代谢综合征，建立大动物PAD模型。手术切除右髂外动脉并发侧支结扎诱导后肢缺血。缺血3-4周后，通过小型体外离心泵进行定向逆行灌注，以产生持续的血流介导的剪切应力。在整个方案中评估功能、成像和分子终点。结论：这种可重复的猪模型为研究灌注驱动的血管生成和评估新的血流重建治疗PAD提供了一个代谢相关的平台。它解决了临床前血管研究中一个关键的翻译缺口。

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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来源期刊

Journal of Vascular Research 医学-生理学

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.