Studying the biological processes that lead to the development of heart disease is essential in the study of preventive and therapeutic approaches to combat the illness.
One in every four deaths in the US is due to heart disease, and the most common type is coronary heart disease caused by arteriosclerosis, a hardening and thickening of the arteries. Studying the biological processes that lead to the development of arterial disease is essential in the study of preventive and therapeutic approaches to combat cardiovascular disease. In vitro methods important for studying disease mechanisms are challenging because explanted endothelial cells can lose their distinctive characteristics.
In an effort to overcome the challenges to growing endothelial cells in vitro, scientists discovered that the use of two transcription factors, MYCN and SOX17, can indefinitely induce and expand cultured CD34 stem cells (arterial endothelial precursors) derived from human umbilical cord blood or adult bone marrow. The researchers observed that some of the cultured CD34 stem cells lose their endothelial traits and take on the characteristics of connective tissue cells through endothelial-to-mesenchymal transition (EndoMT), a process that is key in the development of cardiovascular diseases. Given that some cells do not convert, identifying the molecular differences between these and those that do convert can help in understanding the specific changes leading to EndoMT.
The transitioned mesenchymal cells can easily be identified in culture by their star-shaped appearance and the tendency to clump and stick to one another, a feature that causes the cells to build up in diseased arteries and impede adequate blood flow. The finding that the in vitro CD34 stem cells comprise two types, one that undergoes EndoMT and another that is resistant to transition, can help scientists to better understand the cardiovascular disease progression process and to develop drugs that can prevent the progression.
Results of the in vitro studies is another significant step in uncovering the molecular and cellular differences between transitioned and healthy endothelial cells. Identifying the reprogramming events that lead to EndoMT and the factors that distinguish transitioned and healthy cells could serve as targets of new drug classes that can combat the cardiovascular disease epidemic. Personalized medicine efforts can also be strengthened by more accurately identifying individual disease risk and response to new therapies.
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New stem cell method sheds light on a tell-tale sign of heart disease. (2018). ScienceDaily. Retrieved 18 May 2018, from https://www.sciencedaily.com/releases/2018/01/180109124957.htm