Efficient reabsorption of transintestinally excreted cholesterol is a strong determinant for cholesterol disposal in mice

Abstract

Atherosclerosis, which can lead to coronary artery disease and cerebrovascular accidents, accounts for approximately 50% of deaths in Westernized countries, and its prevalence is increasing in low-and middle-income countries (1, 2). The etiology of atherosclerosis is complex, and risk factors are both genetic and environmental. Hypercholesterolemia can contribute to the development of atherosclerosis via the accumulation of cholesterol from LDLs in the arterial vessel wall (2, 3). Treatment options for hypercholesterolemia and atherosclerosis include lifestyle modifications (e.g., ceasing to smoke, increasing physical activity, improving diet quality) (4, 5), as well as drugs targeted at cholesterol metabolism. The most widely prescribed class of drugs are statins that inhibit hepatic cholesterol synthesis. Unfortunately, statins reduce the cardiovascular disease risk only by 15% to 37% (6). Novel proprotein convertase subtilsinkexin type 9 inhibitors show promising results but also limitations (7). Therefore, more effective or adjunct treatments are needed for the prevention and treatment of atherosclerosis.