What Is Atherosclerosis?
Atherosclerosis is the leading cause of death and disability in developed nations. A variety of risk factors predispose to the development of atherosclerosis, which subsequently affects various regions of the circulation with significant clinical manifestations depending on the circulatory bed affected. Atherosclerosis of the coronary arteries can lead to myocardial infarction and angina pectoris, whereas atherosclerosis of the arteries supplying the central nervous system may cause a life-threatening stroke.
Atherosclerosis
The major risk factors associated with atherosclerosis are hyperlipidemia, diabetes, hypertension, and endothelial injury etc. A recent study reports that there may be unregulated cell growth that could be the major driving factor behind atherosclerosis, contradicting the previously hypothesized plaque formation from lipid accumulation in sites of endothelial injury.
Blood vessel proliferation associated with Atherosclerosis
Researchers from the Stanford School of Medicine have shed light on a newly identified major risk factor for the development of atherosclerosis. Unregulated multiplication of inflamed vascular smooth muscle may be the initiating factor responsible for the formation of atherosclerotic plaques.
An atherosclerotic plaque is composed of accumulated dead tissue, inflammatory cells, and cholesterol. Rupture of these plaques can lead to fatal thrombotic plaques, leading to sudden death from stroke or cardiovascular disease.
However, this risk factor is not a newly proposed finding. In 1973, atherosclerotic vessel plaques were found to be made predominantly of arterial smooth muscle cells, which replicated in an unregulated manner over time. In spite of this, the idea has not been researched until now.
Researching An Old Concept
Leeper, along with his colleague, renewed interest in this concept and even went on to demonstrate that the vessels affected by atherosclerosis inhibited the immune system from phagocytosis of the plaques. This finding led the researchers to believe that the blood vessels may be a part of the disease process itself.
In order to find out how the rapidly proliferating blood vessel cells arise, the researchers examined the muscle cells with a plaque by using mice. A cell marked with the color red is observed for multiplication as its progeny divides with the same color. With this method, the researchers discovered that a single cell proliferates in an abnormal manner, constricting blood flow.
In normal situations, these abnormally proliferating cells are removed by the immune system. But due to loss of normal regulatory function, the smooth muscle cells of the atherosclerotic vessels display a marker on their cell surface, CD47, which is a marker that tells the immune cells to recognize the cells as self and prevent immune clearance.
“The combination of hyperproliferative growth and increased expression of ‘don’t eat me’ signals that frustrate immune mechanisms that would otherwise control them gives these cells a competitive advantage over normal smooth muscle cells,” said Leeper.
References
Wang, Y., Nanda, V., Direnzo, D., Ye, J., Xiao, S., Kojima, Y., Howe, K. L., Jarr, K., Flores, A. M., Tsantilas, P., Tsao, N., Rao, A., Newman, A. A. C., Eberhard, A. V., Priest, J. R., Ruusalepp, A., Pasterkamp, G., Maegdefessel, L., Miller, C. L., […] & Leeper, N. J. (2020). Clonally expanding smooth muscle cells promote atherosclerosis by escaping efferocytosis and activating the complement cascade. Proceedings of the National Academy of Sciences of the United States of America, 117(27), 15818–15826. https://doi.org/10.1073/pnas.2006348117
