Date of Award
Doctor of Philosophy (PhD)
Dr. Suhail Al Salam
Dr. Abderrahim Nemmar
Dr. Abdu Adem
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 galactoside 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 levels 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 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 vii 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 microenvironment 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.
I would like to express my sincere gratitude to my supervisor Dr. Suhail Al-Salam. He has been a tremendous mentor. I wish to thank him for his continuous encouragement, support and trust in my capabilities which helped me grow as a scientist. I have learned a lot from him about life and his advice has been priceless. I would also like to thank my advisory committee members, Professor Abdu Adem, Professor Nemmar, and Professor Bassam Ali for their brilliant suggestions and for facilitating my work by providing all the help I needed from their laboratories. A special thanks to my friend, Naheed who has been my teacher, my confidante and my critic all at the same time. I am deeply grateful to Loay, Azeem, Dr. Lammers, Shekar and Mr. Singh for teaching me the required research techniques. I am also thankful to Hiba and Manjusha for assisting me in our lab. I am grateful to my fellow PhD students and friends, especially Amal and Nadia A. I was new to the UAE and did not know anyone here but they made me feel like one of their own and during our times of tribulations of PhD we forged a deep friendship that I will cherish forever. I am indebted to my parents for giving me a wonderful environment to grow up in and develop my confidence. They have always supported and encouraged me to find and realize my full potential. I am also grateful to my mother-in-law for her prayers and her help with my children in my hours of need. Thanks to my dear husband, Ehtisham, whose unconditional love and support made it possible for me to successfully complete my PhD. It was through his patience and practical help that I was able to meet the challenges of being a wife and a mother along with competing demands of research, study and personal development. Last but not the least, I owe a lot to my two sons, Maaz and Raaid. They are the joy of my life and they make everything worthwhile.
Hashmi, Satwat, "HYPOXIC SIGNALS IN THE ISCHEMIC MYOCARDIUM: ROLE OF GALECTIN-1 AND GALECTIN-3" (2014). Dissertations. 25.