Schematic representations of the mechanism of CA. a – normal coronary artery. Coronary tunica intima forms DIT with biglycan accumulations in the outer DIT, which is most distant from the arterial lumen. b – DIT enlarged by cell proliferation and matrix production. Cells in the outer DIT underwent hypoxia due to increased diffusion distance. c – neovascularization of the outer DIT from adventitial vasa vasorum. Newly formed vessels are highly permeable. d – biglycan of the outer DIT comes in direct contact with blood LDL-C, which facilitates binding, retention and deposition of LDL-C in outer DIT, while inner DIT is free from lipoproteins. This schematic stage d corresponds to fatty streak Grade 1 and Grade 2 in the Nakashima et al. study . Please note, in the schematic of a normal coronary artery (a), the number of DIT layers shown is less than my estimation in the text. This alteration was necessary to present half of the arterial circumference and emphasize DIT enlargement at the same time in the picture.