Molecular Imaging of Apolipoprotein B-100 in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy

Abstract

SummaryApolipoprotein B-100 (ApoB-100) 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 ApoB-100 in human coronary artery wall. Deposition of native ApoB-100 in excised human coronary plaques and normal segments classified by conventional angioscopy was investigated by color fluorescent angioscopy (CFA) and microscopy (CFM) using Nile blue dye (NB) which elicits a golden fluorescence characteristic of ApoB-100 as a biomarker. By CFA, the % incidence of ApoB-100 was 20 in 40 normal segments, 38 in 42 white, and 11 in 35 yellow plaques (P < 0.05 versus white plaques). There was no significant difference in detection sensitivity between CFA and luminal surface scan by CFM. By CFM transected surface scan, ApoB-100 deposited in superficial, deep, and/or in both layers. Deposition in both layers was frequently observed in white plaques and yellow plaques without necrotic core (NC), less frequently in normal segments, and rarely in yellow plaques with NC. (1) Taking into consideration the well known process of plaque growth, the results suggest that ApoB-100 begins to deposit before plaque formation, increasingly deposits with plaque growth, and disappears after necrotic core formation. (2) CFA is feasible for imaging of ApoB-100 in human coronary artery wall. (Int Heart J 2013; 54: 68-74) Key words: Nile blue dye, Color fluorescent microscopy I n addition to a role in the formation of low-density lipoprotein (LDL), apolipoprotein B-100 (ApoB-100) is itself a risk factor for cardiovascular events such as coronary artery disease; high plasma levels of ApoB are associated with development of major vascular events; 1,2) the ApoB / ApoA-1 ratio has greater risk of coronary artery disease;3) higher incidence of coronary stent occlusion in patients with high level of ApoB; 4) Apo B is a predictor of fatal cardiovascular events; 5) a high level of ApoB remains at increased cardiovascular events despite lowered levels of LDL in statin-treated patients, 6) and therapies have been directed to reduce plasma levels of this lipid component. 7)To date, molecular imaging of the substances involved in atherosclerosis has been performed by various imaging techniques, [8][9][10][11][12][13][14][15][16]) but visualizing native ApoB-100 in the vascular wall, including that of the coronary artery, has not been successful. Therefore, it is not known in what type of atherosclerotic lesion or where in the vascular wall that ApoB-100 is deposited, or how it participates in atherosclerosis initiation and progression.If it could be visualized in the vascular wall, the role of ApoB-100 in atherosclerosis could be clarified objectively.Color fluorescent angioscopy (CFA) is a high-resolution imaging technique that enables percutaneous two-dimensional imaging of the vascular wall from within. We have successfully used CFA or near-infrared fluorescent angioscopy to image the lipid components, such as oxidized low-density...

High-Resolution Angioscopic Imaging During Endovascular Neurosurgery

“…In the case of atherosclerosis, a significant body of work already exists describing the utility of angioscopic imaging in assessing plaque risk factors such as evidence of hemorrhage and lipid content,4,16,17 which has been collected primarily with crude angioscopes in the coronary arteries. The greatly increased resolution of the SFE may allow for better definition of the marginal extent of an atherosclerotic plaque within the cervical carotid arteries and intracranial vasculature and, with future human studies, may identify features associated with embolic risk beyond the basic size and color metrics known today.…”

Recent Advances in Fluorescent Angioscopy for Molecular Imaging of Human Atherosclerotic Coronary Plaque

“…ApoB-100 as visualized by golden fluorescence was found to be distributed alone or co-distributed with LDL ( Fig. 8 ) 36) . The red fluorescence of LPC with both “A” and “B” imaging was elicited after the administration of TB to both white and yellow plaques detected by conventional angioscopy 27) .…”

“…NB has been used as an electromechanical biosensor of DNA 34) . This dye elicits brown fluorescence of LDL and golden fluorescence of ApoB-100 with “B” imaging 35, 36) . FG elicits a brown fluorescence of HDL and a red fluorescence of LDL and LPC with “B” imaging 37, 38) .…”

“…Constructed using data from our studies [25, 27, 33, 35, 36, 37, 38, 39]. The autopsy subject group differed for substances examined.…”

Dye-Staining Angioscopy for Coronary Artery Disease

“…Also, triglyceride and apolipoprotein B-100, which comprise LDL, also became visible [25]. Further, high-density lipoprotein (HDL) which counteracts with oxLDL became visible (Fig.…”