Paclitaxel Mortality in Peripheral Artery Disease

Abstract

Peripheral artery disease is a matter of global concern that affects 200 million people and is associated with decreased arterial perfusion in the extremities. The most plausible pathomechanism involves the formation of atheromas which subsequently cause occlusive atherosclerosis that impinge blood supply. Atheroma formation involves endothelial dysfunction with an accumulation of LDL (Low-density lipoprotein) that subsequently become oxidized and consumed by macrophages to form foam cells. The foam cells will release factors such as MMPs (Matrix metalloproteinases) and PDGF (platelet derived growth factor) that induce the proliferation and migration of smooth muscle cells, forming atheroma. Furthermore, endothelial cell damage can cause a loss of protective mechanisms, such as a reduction in the release of protective vasodilatory prostaglandins and Nitric Oxide. Atherosclerosis formation also decreases oxygen diffusion to the arterial media, resulting in atrophy in the vessel wall and ischemia. Additionally, chronic transmural inflammation cyclically releases increased MMPs and elastases that expand the arterial wall while degrading the protective collagen.