Effects of Macrophages with Dying Heart Cells

Lecture Centre Concourse

Cardiovascular disease involves degraded or dying cells, caused from myocardial infarction, commonly known as a heart attack. When cardiomyocytes, or heart muscle cells, do not receive a high supply of nutrients and oxygenated blood, proper heart functioning is affected, resulting in MI. One cause of this is atherosclerosis. This is a disease when the arterial lumen becomes narrowed due to plaque build-up. Plaque forms when fat, cholesterol, protein, calcium, and white blood cell deposits gradually build up in the inner artery walls, which progressively impedes the arterial blood flow supply, eventually causing organ cell death. The lipids, and most especially the immune factors in this disease contribute to our immune system. This system is responsible for protecting the body from pathogens by the mechanisms of physical or chemical barriers, innate immunity, and adaptive immunity. During these immune responses, immune cells cause for the death of other cells that have been infected or may be abnormal. Cell death is also influenced by our complement system, which “complements” or “enhances” or innate immune system. Complement system proteins, ranging from C1 to C9, become activated when they encounter a pathogen, and mark them for destruction by phagocytes. Macrophages are phagocytic cells that help the body eliminate invading foreign substances that may be harmful to our bodies. There are three distinct complement pathways that lead to the activation of the complement protein, C3. C3 is responsible for many functions of the complement system. There were two aims of this research study. The first aim was to study the reaction of macrophages when encountering a dying heart cell. The heart cells were injured, mimicking a heart attack situation, then the macrophages were added to see how they react. The second aim was to study if C3 played a role in the cell death of heart muscle cells in hypoxic conditions. In this study, the human cardiomyocyte cell line, AC16, was used to study the developmental regulation of cardiomyocytes. A chemical inducer of hypoxia, cobalt (II) chloride hexahydrate, was used to manipulate the cardiomyocytes to mimic the phenomenon of a myocardial infarction. The cardiomyocytes were also put under the treatment of C3 knockout, meaning lack of C3, and wild type serums and then combined with the macrophages to observe the effects on the heart cells.