Research conducted at the University of Virginia School of Medicine highlights various false beliefs and assumptions doctors have regarding the basic composition and formation of atherosclerotic plaques. The findings, published online in the journal Nature Medicine, outline new theories regarding the treatment and management of atherosclerosis, and hopes that the new discoveries will force researchers to reconsider their previous strategies.
Atherosclerosis is a condition where plaques build up in the arteries and cause blockages in the flow of blood and oxygen, causing strokes and heart attacks. Gary K. Owens, PhD, from UVA’s Robert M. Berne Cardiovascular Research Center elaborated that complications resulting from atherosclerosis – most commonly the end-stage of the disease where the plaque ruptures the vessels – was the leading cause of death around the world. Rupturing of a plaque leads to the formation of a big clot that blocks the flow of blood downstream, eventually inducing a heart attack. Moreover, the clot may also travel to and block a blood vessel in the brain, resulting in a stroke. Thus, understanding the mechanisms that keep the plaques stable is very important.
Presently, doctors believed that smooth muscle cells enhances elasticity in the blood vessels) helped manage things. They would travel from their normal position within the walls of blood vessels into the plaque, in an attempt to seal off accumulating fats, dead cells and harmful compounds. It was believed that the more smooth muscle there were – especially in the innermost layer of the blood vessel (fibrous cap) – the more stable the plaques would be.
The present research has revealed the prior concepts as inadequate. “Eighty-two percent of the smooth muscle cells within advanced atherosclerotic lesions cannot be identified using the typical immunostaining detection methods because the lesion cells down-regulate smooth muscle cell markers”, remarked Owen. “This shows that we have grossly underestimated how many smooth muscle cells are in the lesion”. The findings suggest that they themselves might be involved in forming the plaque.
What makes things more complicated is the fact that a certain amount of smooth muscle cells were being misidentified as macrophages (immune cells), whereas certain macrophage-derived cells were camouflaged as smooth muscles cells. Some of the latter were also seen converting into cells similar to myofibroblasts and stem cells. Owens stated that these discoveries have created a complex situation for scientists.
Discovery Of Novel Findings About Atherosclerosis
Laura S. Shankman, a PhD student in Owens lab managed to overcome the limitations of conventionally used methods for identifying smooth muscle cells in plaques. By genetically tagging the cells in their early developmental stages in mice, she was able to track them and their descendants, even if they changed forms. Atherosclerosis was then allowed to develop and its progress, along with the cells, was monitored.
Furthermore, Shankman identified a vital gene – Klf4 – that might be associated with regulating the transitions of smooth muscle cells. Selectively, knocking out this gene in smooth muscle cells significantly decreases the surface area of atherosclerotic plaques and seems to enhance their stability. More interestingly, loss of the gene did not affect the amount of smooth muscle cells in the plaques, rather it altered their functional properties to become more beneficial in disease pathogenesis.
Both of Shankman’s findings raise pertinent questions about previous beliefs and studies regarding atherosclerosis and its management. Most importantly, they highlight that controlling smooth muscle cells within the lesions could be extremely effective in treating the disease.