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

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.