The most common cause of peripheral arterial disease is the buildup of plaque inside blood vessels called arteries. Plaque is made up of excess cholesterol, calcium, and other substances in your bloodstream. Over time, plaque builds up in the walls of the arteries, including the arteries that feed your legs. The plaque deposits decrease the space through which oxygen- and nutrient-rich blood can flow. Poor blood flow "starves" the muscles and other tissues in the lower body.