Molecular Mechanisms of Flow-dependent Arterial Remodeling in Peripheral Arterial Disease

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Abstract Due to both aging and the improved longevity of patients with cardiovascular disease, the US population is at an ever-increasing risk of developing peripheral arterial disease. Patients with peripheral arterial disease have stiffened arteries, and peripheral arterial disease doubles patients' cardiovascular mortality. Importantly arterial stiffening is thought to be reversible. While there are a number of factors that lead to atherosclerosis, we propose that there are unique molecular signatures in arteries of patients with PAD that are related to the stiffness and flow conditions of these arteries. We have identified an important role for thrombospondin-1 in these conditions. Here we will identify and test the modifiability of these pathways using in vitro and in vivo models of PAD conditions. In order to test translation of this work, human tissue will be used to test critical findings. Positive results will be useful in developing targeted strategies that disrupt these pathways and improve arterial health in our patients.