Original ArticleCardioprotective Effect of VEGF and Venom VEGF-like Protein in Acute Myocardial Ischemia in Mice: Effect on Mitochondrial FunctionMessadi, Erij VMD, PhD*,‡,§; Aloui, Zohra PhD§,¶; Belaidi, Elise PhD‖; Vincent, Marie-Pascale MSc*; Couture-Lepetit, Elisabeth PharmD‖; Waeckel, Ludovic PhD*; Decorps, Johanna PhD‖; Bouby, Nadine PhD*; Gasmi, Ammar PhD†,§,¶; Karoui, Habib PhD§,¶; Ovize, Michel MD, PhD‖; Alhenc-Gelas, François MD, PhD*; Richer, Christine PharmD, PhD*Author Information *INSERM U872, Centre de Recherche des Cordeliers, Paris, France; Université Paris-Descartes; Université Pierre and Marie Curie, Paris, France; ‡Institut Pasteur de Tunis, Laboratoire des venins et biomolécules thérapeutiques, Tunis, Tunisia; §Université Tunis El Manar, Tunis, Tunisia; ¶Institut Pasteur de Tunis, Laboratoire d’Epidémiologie moléculaire et Pathologie expérimentale appliquée aux maladies infectieuses LR11IPT04, Tunis, Tunisia; and ‖INSERM U1060-CarMeN, Lyon, France. Reprints: Christine Richer-Giudicelli, PharmD, PhD, INSERM U872, Centre de Recherches des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France (e-mail: email@example.com). Supported by INSERM, Paris-Descartes and Pierre et Marie Curie Universities, the Institut Pasteur de Tunis, the Réseau International des Instituts Pasteur (RIIP), and the Ministère de l’Enseignement Supérieur et de la Recherche de Tunisie. E. Messadi was supported by a grant-in-aid from the Pasteur Institutes Network. The authors report no conflicts of interest. † Deceased. Received September 24, 2013 Accepted November 01, 2013 Journal of Cardiovascular Pharmacology: March 2014 - Volume 63 - Issue 3 - p 274-281 doi: 10.1097/FJC.0000000000000045 Buy Metrics Abstract Abstract: Coronary endothelial dysfunction is involved in cardiac ischemia–reperfusion (IR) injury. Vascular endothelial growth factor (VEGF) activates endothelial cells and exerts cardioprotective effects in isolated hearts. The recently discovered viper venom protein called increasing capillary permeability protein (ICPP) exerts VEGF-like effects in endothelial cells. We examined whether VEGF or ICPP can influence IR outcome in vivo in mice. Dosages of VEGF and ICPP were determined by preliminary blood pressure study. In IR, both the proteins administered intravenously at reperfusion reduced infarct size (IS) by 57% for VEGF and 52% for ICPP (P < 0.01). Pretreatment with a selective VEGFR2 receptor antagonist abolished the reduction in IS. VEGF and ICPP induced ERK phosphorylation in the myocardium. IR triggered mitochondrial pore opening and impaired mitochondrial respiratory function. These effects of IR were prevented by VEGF or ICPP, which increased mitochondrial calcium retention capacity by 37% compared with saline (P < 0.05) and improved mitochondrial respiratory function (by 71% and 65%, respectively for state 3, and 51% and 38% for state 4, P < 0.01 for VEGF). Thus, intravenous administration of VEGF or ICPP at reperfusion largely reduces IS in IR, through stimulation of VEGFR2 receptors. This effect is mediated, at least in part, by improvement of IR-induced mitochondrial dysfunction. © 2014 by Lippincott Williams & Wilkins.