An alternative perspective on the challenges facing science today
Your cells die every day. Don’t worry, your body is protecting itself. In a process known as apoptosis or programmed cell death, cells that are no longer needed commit suicide. Some cells are only required for a short time, they maybe infected by a virus or develop harmful cancerous mutations. Cell death is also an essential part of development from an embryo. For example mouse paws begin as spade-like structures and only form the individual digits as the cells in between die [1]. During apoptosis the cells fragment into smaller apoptotic bodies, and their cell surface is flipped open to display lipid molecules called phosphatidylserines, which act as an “eat me” signal to recruit cells called macrophages to engulf them, before their contents spill out and damage the surrounding tissue. This is a process known as efferocytosis.
However cell death is not always so orderly. Some cells suffer premature death known as necrosis, where they burst open for various reasons such as infection, physical trauma or extreme temperatures. However as the cell’s contents are released into the open, an inflammatory response is triggered, so the macrophages sent to engulf these cells release substances that can damage the surrounding tissue, resulting in a build-up of dead cells. It is this damaging chain of events that often occurs in atherosclerosis; the build-up of fatty plaques which can block arteries or trigger blood clots leading to heart attacks, strokes or tissue death, known as ischaemia. As fatty lipid molecules (primarily LDL or ‘bad’ cholesterol) build up in arteries, they act like damage signals. Macrophages recognise these damage signals as if it is phosphatidylserine, and engulf the lipids to become what is known as a foam cell; a cell full of lipid. A healthy macrophage can repackage the LDL into larger HDL cholesterol, which is released back into the bloodstream to be excreted by the liver. The foam cell can also leave the atherosclerotic plaque to be disposed of via lymphatic vessels, thus shrinking the plaque. However, foam cells can be overwhelmed by engulfing excess cholesterol, increasing harmful inflammatory signals, stress and apoptosis. But all is not lost here. If other macrophages clear the dying foam cells, less harm will be done. The problem is the increased inflammation renders efferocytosis defective, resulting in a process called secondary necrosis. Here apoptotic bodies swell and burst open, as they haven’t been cleared in time. As a result, a large amount of cell debris builds up inside the atherosclerotic plaque, creating what is referred to as a necrotic core. The core is pro-thrombotic when it is exposed to clotting factors in the bloodstream.
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AuthorDr. Anusha Seneviratne This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Categories
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March 2020
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