Molecular Imaging of Native Low-Density Lipoprotein by Near-Infrared Fluorescent Angioscopy in Human Coronary Plaques

Uchida, Yasumi; Yoshida, Tomoe; Shimoyama, Ei; Uchida, Yukiko

doi:10.1016/j.amjcard.2015.12.004

Cited by 7 publications

(10 citation statements)

References 19 publications

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“…The in vivo incidence of LDL observed by NIRFA using ICG as a biomarker was similar to that in the ex vivo NIRFA study ( Fig. 11 ) 42) . HDL was also visualized in patients by CFA using FG as a biomarker with a result similar to that in the ex vivo study 37, 38) .…”

Section: Fluorescent Angioscopy In Patients With Coronary Heart Diseasesupporting

confidence: 80%

“…The percent (%) incidence of LDL increased with plaque growth and decreased in the mature stage as in CFA study. The peak incidence of LDL with NIRFA was higher than that with CFA, probably because of the difference in visualization depth (i.e., 700 µm with NIRFA vs. 200 µm with CFA 42) . There was no significant difference in the incidence of LDL between NIRFA and immunohistochemical staining 42) .…”

Section: Molecular Imaging Of Lipoproteins In Coronary Plaques By Nirmentioning

confidence: 93%

“…LDL exhibits a NIRF in the presence of ICG 42) . Cholesterol, cholesteryl esters, and calcium phosphate individually do not exhibit NIRF but do so in the presence of β -carotene, which is known to co-deposit with lipotropic substances in atherosclerotic lesions.…”

Section: Fluorescence Of the Major Substances Comprising Atheroscleromentioning

confidence: 99%

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

Uchida¹

2017

JAT

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Purpose of Review: In vivo imaging of the native substances, including lipoproteins, that comprise human atherosclerotic plaques is currently beyond the scope of any available imaging techniques. Color and near-infrared fluorescent angioscopy (CFA and NIRFA, respectively) systems have been recently developed for molecular imaging of lipoproteins within the human coronary arterial wall ex vivo and/or in vivo. The author reviews recent findings on lipoprotein deposition in human coronary plaques obtained by these imaging techniques.Recent Findings: Using specific biomarkers, native pro-atherogenic substances such as oxidized low-density lipoprotein (ox-LDL), LDL, triglycerides (TG), apolipoprotein B-100 (ApoB-100), and lysophosphatidylcholine (LPC), and the anti-atherogenic substance such as high-density lipoprotein (HDL) were visualized by CFA, and LDL and cholesterol by NIRFA, in coronary plaques obtained from autopsy subjects. The relationship between incidence and plaque morphology differed for each substance. The incidence of ox-LDL and LDL on color fluorescence microscopy correlated well with that observed using immunohistochemical techniques. During coronary catheterization in patients, ox-LDL, LDL, and HDL in coronary plaques were visualized by CFA or NIRFA.Conclusions: Using CFA or NIRFA, the distribution of the major native pro-atherogenic and antiatherogenic lipoproteins and their components within human coronary plaques can be evaluated ex vivo and/or in vivo. Fluorescent angioscopy could help our understanding of the molecular mechanisms of coronary atherosclerosis and in the evaluation of the effects of therapy targeting the substances comprising atherosclerotic coronary plaques.

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Section: Fluorescent Angioscopy In Patients With Coronary Heart Diseasesupporting

confidence: 80%

Section: Molecular Imaging Of Lipoproteins In Coronary Plaques By Nirmentioning

confidence: 93%

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

Uchida¹

2017

JAT

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“…TG did not autofluoresce, but it presented a brown fluorescence in the presence of 3-ANA. This fluorescent color was not exhibited by any of the other major known substances that comprise atherosclerotic plaques, 2,4 indicating that this fluorescent color was characteristic of just TG. Figure 1 shows a white plaque by conventional angioscopy.…”

Section: Resultsmentioning

confidence: 89%

“…This in vitro study was carried out with the approval of the Ethical Committees of Japan Foundation for Cardiovascular Research, Funabashi-Futawa Hospital and Toho University. After obtaining the written informed consent of the families concerned, 29 coronary arteries (17 left anterior descending arteries, 5 left circumflex arteries, and 7 right coronary arteries) were excised from 19 successive autopsy cases from April 1, 2008, to November 1, 2014 (age 61 AE 3 years, 7 women and 12 men): death from acute myocardial infarction (4), aortic dissection (2), diabetic nephropathy (5), cerebral infarction (2), pancreatic carcinoma (1), hepatocellular carcinoma (3), and gastric cancer (2). The remaining 28 arteries were difficult to excise or used for other purpose.…”

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confidence: 99%

Imaging of Triglycerides in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy

Uchida

Hiruta

et al. 2016

The American Journal of Cardiology

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Native triglycerides (TG) deposited in the human vascular wall is not measurable or visible in vivo to date. We discovered that by exciting fluorescence at 345 nm and emitting at 420 nm, 3-amino-4-hydroxy-5-nitrobenzene sulfonic acid monohydrate (3-ANA) elicits a brown fluorescence that is characteristic of just TG. Therefore, localization of TG in coronary plaques and normal segments that were obtained from 19 human autopsy cases was examined by color fluorescent angioscopy (CFA) and microscopy using 3-ANA as a biomarker of TG. By CFA, the percentage (%) incidence of TG in 23 normal segments, 13 white plaques without lipid deposition, 18 white plaques (growth stage) with lipid deposition, 11 yellow plaques without necrotic core (mature stage), and 12 yellow plaques with necrotic core (advanced mature stage) was 95, 92, 50, 27, and 25, respectively. By color fluorescent microscopy, TG deposited mostly in the fibrotic area of the plaques. Contrary to the general belief that TG amount increases with plaque maturation, the results indicated that TG was deposited in most of the normal coronary segments, but the amount decreased with plaque maturation. If 3-ANA becomes applicable clinically, the CFA system could be used for imaging TG within coronary plaques in patients in vivo.

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Fluorescent angioscopic imaging of calcium phosphate tribasic: precursor of hydroxyapatite, the major calcium deposit in human coronary plaques

Kobayashi

Nakagawa

Shirai

et al. 2017

Int J Cardiovasc Imaging

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Coronary calcification is a risk factor for ischemic heart disease. Hydroxyapatite that is formed by polymerization from calcium phosphate tribasic (CPT) is the major constituent of coronary calcium deposits. If CPT could be visualized, coronary calcification could be predicted and prevented. We discovered that when CPT and collagen I, the main constituent of collagen fibers, are mixed with lac dye (LD) and then exposed to fluorescent light excited at 345 ± 15 nm and emitted at 420 nm, a purple fluorescence that is characteristic of CPT only is elicited. So, we examined localization of CPT and its relation to plaque morphology by color fluorescent angioscopy (CFA) or microscopy (CFM) in 24 coronary arteries obtained from 12 autopsy subjects. By CFA, the incidence (%) of CPT as confirmed by purple fluorescence in 15 normal segments, 25 white plaques, 14 yellow plaques without necrotic core (NC) and 8 yellow plaques with NC was 20, 36, 64 and 100 (p < 0.05 vs. normal segments), respectively. By CFM, the CPT was either deposited alone amorphously or surrounded hydroxyapatite that was identified by Oil Red O, methylene blue and von Kossa’s stain. The results suggested that CFA using LD is feasible for imaging CPT, that is a precursor of hydroxyapatite, in human coronary plaques, and this technique would help prediction and discovery of a preventive method of coronary calcification.Electronic supplementary materialThe online version of this article (doi:10.1007/s10554-017-1142-y) contains supplementary material, which is available to authorized users.

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Molecular Imaging of Native Low-Density Lipoprotein by Near-Infrared Fluorescent Angioscopy in Human Coronary Plaques

Cited by 7 publications

References 19 publications

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

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

Imaging of Triglycerides in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy

Fluorescent angioscopic imaging of calcium phosphate tribasic: precursor of hydroxyapatite, the major calcium deposit in human coronary plaques

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