Hypoxic signals in the Ischemic Myocardium: Role of Galectin-1 and Galectin-3
Abstract
Myocardial Infarction is the most serious manifestation of coronary artery disease and the cause of significant levels of mortality and morbidity worldwide. Galectin-1 (GAL-1) and Galectin-3 (GAL-3) are beta galoctoside binding lectins with diverse functions. Hypoxia inducible factor-1 alpha (HIF-1α) is a transcription factor mediating early and late responses to myocardial ischemia. We aim to study the direct effects of ischemia on GAL-1, GAL-3 and HIF-1α in the heart. Male C57B6/J and GAL-3 knockout mice were used for our two disease models. In the myocardial infarction (MI) model, the left anterior descending artery of the heart is permanently ligated to create ischemia in the anterior myocardium. In the Ischemia Reperfusion model (IR), the artery is temporarily ligated for a specific period of time and then reperfusion is established. Heart samples were processed for immunohistochemical and immunofluorescent labeling, western blotting, enzyme linked immunosorbent assay and quantitative real time PCR. Inflammatory, Apoptotic and Oxidative stress markers were also studied. We show for the first time that GAL-1, GAL-3 and HIF-1α in the left ventricle are raised in early ischemic period in conjunction with a predominant antiapoptotic activity in the heart. Our identification of the pattern of expression of GAL-1, GAL-3 and HIF-1α levels in the heart during the first 24 hours following acute MI has helped in understanding early molecular changes in this event and may provide methods to overcome serious complications. Our work further showed that GAL-3 acted as a regulator of proinflammatory and antiapoptotic mechanisms in the myocardium after myocardial infarction that will shape the future course of the disease. GAL-3 was also shown to interfere with redox pathways controlling cell survival and death and plays a protective role in the pathogenesis of ischemia reperfusion injury in the heart. Our work has contributed in understanding the local in which GAL-3 works in the heart after ischemia/infarction or ischemia-reperfusion and has opened a new window in understanding the exact role of GAL-3 in the heart.