Non-oxidative Modified Low-density Lipoproteins: The Underappreciated Risk Factors for Atherosclerosis

Atherosclerosis, the pathological basis of most cardiovascular diseases, is a main risk factor causing about 20 million deaths each year worldwide. Oxidized low-density lipoprotein is recognized as the most important and independent risk factor in initiating and promoting atherosclerosis. Numerous antioxidants are extensively used in clinical practice, but they have no significant effect on reducing the morbidity and mortality of cardiovascular diseases. This finding suggests that researchers should pay more attention to the important role of non-oxidative modified low-density lipoprotein in atherosclerosis with a focus on oxidized low-density lipoprotein. This review briefly summarizes several important non-oxidative modified low-density lipoproteins associated with atherosclerosis, introduces the pathways through which these non-oxidative modified low-density lipoproteins induce the development of atherosclerosis in vivo, and discusses the mechanism of atherogenesis induced by these non-oxidative modified low-density lipoproteins. New therapeutic strategies and potential drug targets are provided for the prevention and treatment of atherosclerotic cardiovascular diseases.