The Prominin-1-Derived Peptide Improves Cardiac Function Following Ischemia

Abstract

Myocardial infarction (MI) remains the leading cause of death in the western world. Despite advancements in interventional revascularization technologies, many patients are not candidates for them due to comorbidities or lack of local resources. Non-invasive approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been effective in animal models but not in humans likely due to its short half-life and systemic toxicity. Here, we tested the hypothesis that PR1P, a small VEGF binding peptide that we developed, which stabilizes and upregulates endogenous VEGF, could be used to improve outcome from MI in rodents. To test this hypothesis, we induced MI in mice and rats via left coronary artery ligation and then treated animals with every other day intraperitoneal PR1P or scrambled peptide for 14 days. Hemodynamic monitoring and echocardiography in mice and echocardiography in rats at 14 days showed PR1P significantly improved multiple functional markers of heart function, including stroke volume and cardiac output. Furthermore, molecular biology and histological analyses of tissue samples showed that systemic PR1P targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium. We conclude that PR1P is a potential non-invasive candidate therapeutic for MI.

Specific bio‐functionalCBD‐PR1Ppeptide bindingVEGFto collagen hydrogels promotes the recovery of cerebral ischemia in rats

“…27 The specific peptide-PR1P had been shown to promote angiogenesis by targeted binding VEGF and enhancing endogenous VEGF activity, which facilitated the repair of corneal, choroid, ear wound healing and hind limb ischemia. 19 Then PR1P peptides was revealed to 20 and in a mouse model of emphysema, it reduced acute lung injury by promoting the binding of VEGF to endothelial cells. 28 Studies on ONC model showed that PR1P peptide could enhance the effect of VEGF in promoting neuronal survival and ameliorating the neurodegeneration.…”

“…19 And they were also showed to capture and upregulate endogenous VEGF in vivo, so that improved the angiogenesis and functional recovery in hind limb ischemia and myocardial ischemia. 19,20 In addition, a recent study in optic nerve compression (ONC) model, PR1P were demonstrated to enhance the survival of VEGF-driven neurons. 21 Whether these PR1P peptides could serve as anchor for VEGF sustained release?…”

“…These PR1P peptides specifically bond with VEGF and promoted angiogenesis through enhancing the binding of VEGF to its receptor‐VEGF receptor 2 (VEGFR2) and neuropilin‐1 (Nrp1) 19 . And they were also showed to capture and upregulate endogenous VEGF in vivo , so that improved the angiogenesis and functional recovery in hind limb ischemia and myocardial ischemia 19,20 . In addition, a recent study in optic nerve compression (ONC) model, PR1P were demonstrated to enhance the survival of VEGF‐driven neurons 21 .…”

Functional recovery of myocardial infarction by specific EBP‐PR1P peptides bridging injectable cardiac extracellular matrix and vascular endothelial growth factor

“…PR1P could specifically interact with VEGF, stabilize VEGF, and increase the binding of VEGF to its receptors via potentiation of VEGF dimer formation 15 . In different animal models, PR1P was showed to enhance the repair of wound healing, hind limb ischemia and MI, reduced acute lung injury and protected neuron survival 16–18 . PR1P was also used to modify biomaterial scaffold.…”

“…15 In different animal models, PR1P was showed to enhance the repair of wound healing, hind limb ischemia and MI, reduced acute lung injury and protected neuron survival. [16][17][18] PR1P was also used to modify biomaterial scaffold. By chemical covalent coupling, RP1P could immobilize VEGF on nano glasses effectively and increase the bioactivity of material scaffolds.…”