SummaryHigh-density lipoprotein (HDL) plays a key role in reverse cholesterol transport, and halts the progression of atherosclerosis. However, its localization in human vascular wall is not well understood. We discovered that by exciting at 470-nm and emitting at 515-nm light wavelengths, Fast green dye (FG) elicits brown fl uorescence characteristic of HDL only. Therefore, the localization of native HDL in normal segments and plaques in excised human coronary artery was investigated by scanning their transected surface with color fl uorescent microscopy (CFM) using FG as a biomarker, and the relationships between the localization of HDL and morphology of plaques and normal segments classifi ed by conventional angioscopy and histology were examined. The % incidence of HDL in 13 normal segments (NS) with thin is associated with decreased risk of coronary heart disease. 1) Elevating the plasma level of HDL by fibrates is associated with a lower incidence of coronary heart disease.2) Mechanisms by which antiatherogenic HDL reduces atherosclerosis include facilitating cholesterol uptake from cholesterol-loaded macrophage-foam cells in plaques for transport back to the liver, 3,4) a role as an anti-infl ammatory lipoprotein, decreasing oxidized low-density lipoprotein (oxLDL), increasing nitric oxide synthesis, 5) improving endothelial function, and as an antithrombotic agent. 5) Infusions of HDL or its major component, apolipoprotein A-1 (Apo A-1), halt the progression or induce the regression of atherosclerosis. [6][7][8] The relationship between the plasma HDL levels and atherosclerotic lesions has been extensively investigated. Traffi cking HDL movement was performed using gadolinium methianethiosulfonate-labeled ApoA-1 in animal liver and kidney, 9) and using nanocrystals such as Au-HDL and FeO-HDL in the mouse aorta, 10) but imaging of native HDL in the human vascular wall has not been successful to date. Therefore, it is not known in what type(s) of atherosclerotic plaques native HDL deposits, whether this substance deposits in the normal vascular wall, how this substance acts against atherosclerotic plaque growth and destabilization, and whether or not its concentration changes in parallel with that in the plasma. If HDL could be visualized in the vascular wall, the molecular mechanisms by which HDL causes regression of atherosclerosis and whether or not the amount of HDL in the vascular wall is increased by HDL-raising compounds could be clarified more objectively.We recently discovered that Fast green dye (FG), which is used clinically to stain oral mucosal micronuclei for detection of the genotoxicity of antihyperglycemic drugs in patients with diabetes mellitus, 11) intraocular membrane staining, 12) and subchondral bone staining, 13) elicits a brown fl uorescent color from HDL when fl uorescence is excited at 420 ± 20-nm and emitted at 515-nm light wavelengths. Therefore, in the present study, color fluorescent microscopic (CFM) scanning of the transected surface of the excised human coronary artery (bo...