INVESTIGATING THE ROLE OF APOPTOSIS IN CALCIFICATION OF THE AORTIC VALVULAR INTERSTITIAL CELLS

Jebeli, Mahvash

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INVESTIGATING THE ROLE OF APOPTOSIS IN CALCIFICATION OF THE AORTIC VALVULAR INTERSTITIAL CELLS

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Calcification of the aortic valve is a significant source of mortality in the elderly in the US. Even as a serious disease, calcification does not have any permanent therapeutics. Valvular interstitial cells, fibroblastic in nature and located in the middle layer of the aortic valve, are mainly involved in the pathology of this disease. Apoptosis, i.e., programmed cell death, is a crucial phenomenon in the body to maintain homeostasis. Apoptosis is a biological phenomenon that is affected by the collective behavior of the cells, as cells’ behavior defers in the proximity of others. In the early stages of apoptosis, the phosphate head of phosphatidylserine, a phospholipid in the cell membrane, translocates to the outside of the cell. Although a correlation between calcification and apoptosis is shown, no definite reason behind this correlation has been introduced so far. Here, we show how the collective behavior develops, as multicellular bands, in aggregates of valvular interstitial cells and how it leads to changes in mechanical states of the cells demonstrated by the biological markers of low-stress environments such as higher apoptosis. Then, we examine the effect of phosphatidylserine on calcification, indicating the possible role of phosphatidylserine exposure during the early stages of apoptosis in the initiation of calcification. The knowledge obtained from this thesis expands our understanding of fibroblastic collective behavior that leads to different biological phenomena, such as the development of higher apoptosis rates. Further, the results from this research could assist in further investigations on phosphatidylserine's role in calcification. Also, the results of this study could be applied to other fibroblasts, such as human dermal fibroblasts, and similar diseases, such as atherosclerosis.

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