The role of smooth muscle cells in calcification of atherosclerotic plaques

To date, cardiovascular disease poses the foremost cause of global mortality, accounting for more than every third death worldwide. Severe symptoms like strokes are often caused by atherosclerotic carotid artery occlusion, affecting three quarters of the population at 65 years and older. Innovative medicine has the responsibility to reduce hospitalizations and expensive surgical procedures by improving routine diagnostics as well as patient specific medical care. The results presented in this thesis demonstrate that biological processes similar to bone healing can be connected to clinical risk reduction in cases of late stage human atherosclerosis. Moreover, detailed computational analysis of existing noninvasive clinical imaging was utilized to model the impact of patient specific plaque structures on vessel wall stability and cellular composition. Thereby creating a potential pipeline for future predictive vascular disease diagnostics. Proteoglycan 4 emerged as a specific target, marking the onset of osteogenic transformation in atherosclerotic disease progression, with the capacity to modulate smooth muscle cell differentiation. Together, these findings contribute to a better understanding of vessel wall remodeling and vulnerability in patients suffering from atherosclerosis, consequently with the potential to improve diagnostic accuracy and individual risk prediction, warranting further clinical evaluations