Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target

- Consensus hypothesis on pathogenesis of coronary atherosclerosis incorporates misconceptions about human coronary morphology and initial patterns of lipid deposition.
- Initial lipid depositions occur in the deepest region of the coronary tunica intima, making the accepted pathogenesis hypothesis implausible.
- Excessive intimal hyperplasia occurred before lipid depositions, causing hypoxia of deep intimal cells, neovascularization from adventitial vasa vasorum and direct lipid extraction from blood.
- Excessive intimal hyperplasia in the human coronary artery is the initiation of coronary atherosclerosis and constitutes a therapeutic target.

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.