Cardioprotective effects of alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom, on hypoxia-reoxygenation-induced injury in fish

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2019-01, Vol.215, p.67-75
• Main Authors: Monteiro, D.A., Kalinin, A.L., Selistre-de-Araújo, H.S., Nogueira, L.A.N., Beletti, M.E., Fernandes, M.N., Rantin, F.T.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inducing Agents - administration & dosage; Angiogenesis Inducing Agents - therapeutic use; Animals; Aquaculture; Bothrops; Cardiac function; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - therapeutic use; Characiformes; Collagen - metabolism; Coronary Vessels - drug effects; Coronary Vessels - pathology; Coronary Vessels - physiopathology; Crotalid Venoms - chemistry; Desintegrin; Disease Models, Animal; Disintegrins - administration & dosage; Disintegrins - therapeutic use; Excitation Contraction Coupling - drug effects; Excitation-contraction coupling; Fish Proteins - metabolism; Heart - drug effects; Heart - physiology; Heart - physiopathology; Hypoxia/reoxygenation; Injections, Intra-Arterial; Myocardial Contraction - drug effects; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Neovascularization, Physiologic - drug effects; Reptilian Proteins - administration & dosage; Reptilian Proteins - therapeutic use; Snake venom
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2018.10.003

Alternagin-C (ALT-C) is a disintegrin-like peptide purified from Rhinocerophis alternatus snake venom with the property of inducing vascular endothelial growth factor (VEGF) expression, endothelial cell proliferation and migration, and angiogenesis. Therefore, this protein could be interesting as a new approach for ischemic heart diseases, an imbalance between myocardial oxygen supply and demand, leading to cardiac dysfunction. We investigated the effects of a single dose of alternagin-C (0.5 mg kg−1, via intra-arterial), after 7 days, on hypoxia/reoxygenation challenge in isolated ventricle strips and on morphological changes and density of blood vessels of the heart, using fish as an alternative experimental model. ALT-C treatment provided protection of cardiomyocytes against hypoxia/reoxygenation-induced negative inotropism. ALT-C also stimulated angiogenesis and improved excitation-contraction coupling during hypoxic conditions. Our results provide a new insight into a functional role of ALT-C against hypoxia/reoxygenation-induced cardiomyocyte injury pointing out to a potential therapeutic strategy for ischemia-related diseases. [Display omitted] •ALT-C protects against hypoxia/reoxygenation-induced cardiomyocyte negative inotropism.•ALT-C stimulates cardiac angiogenesis.•ALT-C improves the cardiac function increasing the contraction force during hypoxic condition.