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HowToPreventHeartDisease.com |
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How Is Efferocytosis Linked To Heart Disease? High Cholesterol is one of the risk factors of heart disease and stroke. Too much cholesterol in the blood stream can builds up in the walls of arteries, which will narrow the arteries and slow down and block the blood flow to the heart muscle. The blood is supposed to carry oxygen to the heart. So, if the heart is not getting sufficient blood and oxygen, one may suffer chest pain. When the blockage completely cut off the blood supply to a portion of the heart, heart attack may occur. Despite of good control of cholesterol and other risk factors, some individuals’ arteries continue to progressively narrow. Obviously, there ought to be other mechanisms beyond the conventional risk factors that cause heart attack and stroke. First, it is necessary to understand a term called “efferocytosis”. Even as one ages, the body is still constantly renew itself: more than one million cells per second. The ageing cells are removed and replaced by newer cells. This process is known as “programmed cell removal” or efferocytosis, which plays an important role in plaque formation within arteries. In the process of efferocytosis, a regulated protocol exists to ensure the body removes only dead cells and does not engulf healthy cells. The dying cell is engulfed by cells called phagocytes. There are several signaling molecules involved in the communication between a dying cell and a phagocyte. These include: “find me” molecules to attract the phagocytes to the site of cell death, “eat me” molecules on the surface of the dying cells, and bridging molecules that have dual roles of making the dying cells more appetizing to the phagocyte and physically linking the phagocyte to the dying cells. Furthermore, there are also the “don’t eat me” molecules present on the surface of healthy cells to avoid removal of healthy cells.
For almost all organs and tissues, the removal process is extremely efficient, except in degeneration of arteries (also called atherosclerosis), especially heart arteries which is narrowed because of accumulation of cell material and cholesterol. Studies have estimated that there is about a 20-fold reduction in efferocytosis capacity in the plaque. Because of the impaired clearance of cell debris, plaque accumulation and instability are increased. When a phagocyte ingests a dying cell, the cholesterol contents of the dying cell cannot be easily embraced and so are expelled through the wall of the phagocyte to other cholesterol carriers in the blood stream. The accumulated cholesterol in the phagocyte transforms the cell into a "foam cell". The high cholesterol content foam cell is an important cause of atherosclerosis and plaque formation. Since the phagocyte fails to remove the dying cell, the cell breaks up before it is ingested, releasing cell contents that will include chemicals to attract other inflammatory cells and weaken the wall of the plaque, thereby promoting instability of the plaque. Current investigations suggest excessive cell death is the cause of the accumulation of cell debris within the plaque. Instead, it is due to reduced capacity for clearance of cell debris by the phagocytes and the dying cell becoming inedible due to inflammation-induced modification of the signaling molecules as well as accumulation of oxidized or "toxic" low density lipoprotein (LDL) cholesterol. Understanding of impaired efferocytosis should open new ways to treat heart disease. Therapies that can reduce inflammation appear to improve efferocytosis, making removal of dying cells efficient and preventing the accumulation of cell debris in arterial wall plaques. Use of anti-inflammatory agent, anti-TNF (Infliximab or Etanercept) has been shown to reduce plaque formation and protect from getting heart attack. The balance between "eat me" and "don't eat me" molecules extends beyond heart arterial plaques to plaques in the neck that predispose to stroke, as well as to the realm of cancer. In cancer therapy, reduction of "don't eat me" molecules on cancer cells can increase their removal. For instance, anti-tumor antibodies (such as rituximab) synergize with therapies that promote efferocytosis to significantly increase the clearance of cancer cells.
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