The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer – endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendothelial lipoprotein retention initiates the disease. Facts showed: (i) normal tunica intima invariably consists of multiple cellular layers; and (ii) initial lipid depositions occurred in the deepest layers of tunica intima. This review suggests that coronary atherosclerosis starts with pathological intimal expansion, resulting in intimal hypoxia and neovascularization from adventitial vasa vasorum, facilitating lipoprotein extraction by previously avascular deep intimal tissues. Until the hypothesis incorporates real knowledge, our efforts will probably be off-target.

Vladimir M. Subbotin studied biology and medicine at the Novosibirsk Medical School, Russia, and obtained his MD degree in 1969. He received his PhD in 1973 on the study of the human placenta under his mentor and father M.Ya. Subbotin. Later he worked at the Russian Academy of Sciences (Академгородок), and as a volunteer at the Novosibirsk Zoo. Upon immigration to the USA in 1991, Vladimir worked at the University of Pittsburgh, Department of Pathology and Thomas E. Starzl Transplantation Institute. In 2000 he joined Mirus Bio Corporation (now Arrowhead Pharmaceuticals) Madison WI, USA, working on preclinical pathology, drug delivery and theoretical approaches to coronary atherosclerosis and cancer.