Atherosclerosis is a chronic inflammatory disease of the arterial wall and the main cause of cardiovascular disease and cerebrovascular disease. In recent years, the mortality rate of atherosclerotic diseases has become higher and higher. This article aims to study the dysregulation of atherosclerotic vascular endothelial secretion and smooth muscle cell proliferation, and put forward and practice the pathological research of atherosclerotic disease. This article describes in detail atherosclerosis, endothelial dysfunction, and smooth muscle cell proliferation, and studies the causes of atherosclerosis. Research results indicate that atherosclerotic vascular endothelial dysfunction also has a great influence on the proliferation of smooth muscle cells. Many genes and environmental factors can regulate the functions of endothelial cells, vascular smooth muscle cells, and mononuclear macrophages and affect the formation of atherosclerosis. At the same time, diabetes, hypertension, hyperlipidemia, obesity, etc. are the main causes of atherosclerosis. The number of patients with cardiovascular and cerebrovascular diseases dying from atherosclerosis in the country is increasing, and the proportion is close to 30%.