Molecular Imaging of Low-density Lipoprotein in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy

Abstract

ObjectivesLow-density lipoprotein (LDL) is an important risk factor for coronary artery disease. However, its localization in human coronary plaques is not well understood. The present study was performed to visualize LDL in human coronary artery wall.Methods(1) The fluorescence characteristic of LDL was investigated by color fluorescent microscopy (CFM) with excitation at 470-nm and emission at 515-nm using Nile blue dye (NB) as a biomarker. (2) Native LDL in 40 normal segments, 42 white plaques and 35 yellow plaques (20 with necrotic core) of human coronary arteries was investigated by color fluorescent angioscopy (CFA) and CFM.Results(1) NB elicited a brown, golden and red fluorescence characteristic of LDL, apolipoprotein B-100, and lysophosphatidylcholine/triglyceride, respectively. (2) The % incidence of LDL in normal segments, white, and yellow plaques was 25, 38 and 14 by CFA and 42, 42 and 14 by CFM scan of their luminal surface, respectively, indicating lower incidence (p<0.05) of LDL in yellow plaques than white plaques, and no significant differences in detection sensitivity between CFA and CFM. By CFM transected surface scan, LDL deposited more frequently and more diffusely in white plaques and yellow plaques without necrotic core (NC) than normal segments and yellow plaques with NC. LDL was localized to fibrous cap in yellow plaques with NC. Co-deposition of LDL with other lipid components was observed frequently in white plaques and yellow plaques without NC.Conclusions(1) Taken into consideration of the well-known process of coronary plaque growth, the results of the present study suggest that LDL begins to deposit before plaque formation; increasingly deposits with plaque growth, often co-depositing with other lipid components; and disappears after necrotic core formation. (2) CFA is feasible for visualization of LDL in human coronary artery wall.

Localization of Oxidized Low-Density Lipoprotein and Its Relation to Plaque Morphology in Human Coronary Artery

“…In contrast, in this and our previous studies using CFA and CFM, dot-like deposition of lipoproteins, apolipoproteins, cholesterol or cholesterol esters was rare [25], [26], [35], [36]. The difference is possibly related to the cut-off of the low-intensity portions of the obtained images to enhance the high-intensity portions, leading to a dot-like distribution in spectroscopy.…”

Polymer Nanoassemblies With solvato- and halo-fluorochromism for Drug Release Monitoring and Metastasis Imaging

“…NB was selected as a model fluorophore with fluorochromism that changes fluorescence wavelengths depending on the amount of drugs entrapped in nanoparticles as well as the pH of solvents in which nanoparticles are present. Solvato-fluorochromic molecules have been used to detect changes in environmental polarity [33]. Pyrene is a fluorochromic dye commonly used to detect the hydrophobic micelle core environment [34].…”

Imaging of Native High-Density Lipoprotein in Human Coronary Plaques by Color Fluorescent Angioscopy

“…11 FG (Wako Co, Osaka, Japan) was diluted in distilled water to a concentration of 10 −5 mol/L (the maximum concentration at which FG does not precipitate) at 37°C and then added to each of the major substances that comprise atherosclerotic plaque. 13 The consequently evoked fluorescence was photographed at ×40 magnification.…”

“…We have successfully used CFA to image the lipid components of human coronary plaques, such as oxLDL, 11 lysophosphatidylcholine (LPC), 12 LDL 13 and ApoB-100, which comprises low-density lipoprotein (LDL), 13 both in vitro and/or in vivo, but have not attempted imaging native HDL because of the lack of an appropriate, high plasma level of high-density lipoprotein (HDL) is associated with decreased risk of coronary artery disease, 1 and elevating the plasma level of HDL by fibrates is associated with a lower incidence of coronary artery disease. 2 The mechanisms by which anti-atherogenic HDL reduces atherosclerosis include facilitating cholesterol uptake from cholesterol-loaded macrophage-foam cells in plaque for transport back to the liver, 3,4 a role as an antiinflammatory lipoprotein, decreasing the level of oxidized low-density lipoprotein (oxLDL), increasing nitric oxide synthesis, 5 improving endothelial function, and as an antithrombotic agent.…”