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

International Journal of Molecular Sciences

Yuval Tal¹  Irit Adini²  PeterM. Kang³  Etty Grad⁴  HaimD. Danenberg⁴  Avner Adini⁵  BenjaminD. Matthews⁵  RobertJ. D’Amato⁵ 

[1] Allergy and Clinical Immunology Unit and Department of Medicine, Hadassah University Medical Center, Jerusalem 91200, Israel;Department of Surgery, Harvard Medical School, The Center for Engineering in Medicine, Mass General Hospital, Shriners Hospitals for Children Boston, Boston, MA 02114, USA;Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA;Interventional Cardiology, Heart Institute, Hadassah Hebrew University Medical Center, Jerusalem 91200, Israel;Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;

关键词: myocardial infarction;    apoptosis;    angiogenesis;    PR1P;    prominin-1;    VEGF;   

DOI  :  10.3390/ijms22105169

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown