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

Abstract

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.

Lysophosphatidylcholine is a Major Component of Platelet Microvesicles Promoting Platelet Activation and Reporting Atherosclerotic Plaque Instability

“…52,55 Using fluorescent angioscopy, LPC has been detected ex vivo in coronary artery plaques. 56 These data were supported by Ménégaut et al, who reported ex vivo increased levels of 2-arachidonoyl-lysophosphatidylcholine in carotid atheroma plaques of diabetic patients. 57 In agreement with these report, we found LPC to be more abundant in atherosclerotic plaques compared with normal arterial tissues.…”

Myeloid Tribbles 1 induces early atherosclerosis via enhanced foam cell expansion

“…Recent studies have established that oxLDL accumulates steadily in both early-stage (growing) and mature-stage (yellow plaque without a necrotic core) human coronary plaques but that, in more advanced vulnerable plaques (yellow plaques with a necrotic core), this lipoprotein is removed either by metabolism or replacement with other substances, including cell debris ( 2 ). These in vivo data dovetail well with the early in vitro work, which showed that while oxLDL promotes macrophage growth and survival in a dose-dependent manner, beyond a certain lipid concentration, cell death ensues, albeit by an unknown mechanism ( 10 ).…”

“…Atherosclerosis, a progressive disease of arterial blood vessels and the main underlying cause of stroke, myocardial infarction, and cardiac death ( 1 ), is initiated by the conversion of plaque macrophages to cholesterol-laden foam cells ( 2 ) in the arterial intima ( 3 ). In the early-stage atherosclerotic plaque, this transformation is induced by the uptake of both low density lipoprotein-cholesterol (LDL-C) and oxidized LDL (oxLDL) ( 2 , 4 ), which may serve a beneficial purpose ( 3 ); but unrestrained, the crucial function of plaque macrophages in resolving local inflammation is compromised, and the development of unstable, advanced lesions ensues ( 3 ). It has been shown that foamy macrophages are not only less effective in clearing apoptotic cells ( 5 ), they are also more prone to apoptosis ( 6 ), thus increasing secondary necrosis and the release of cellular components and lipids that ultimately form the necrotic core of advanced plaques.…”

Combined Use of Angioscopy and Intravascular Ultrasonography for Diagnosis and Evaluation of Surgical Repair of Aortic Disease

“…The cardiac chambers and valves were examined by Uchida. 35,36) Cellular AS, dye-staining AS and molecular AS were developed and used clinically by Uchida et al, 37) Uchida, 38) Uchida et al, 39,40) Uchida and Maezawa, 41) Uchida et al, 42,43) Uchida, 44) Uchida et al, 45,46) Uchida, 22,47,48) Uchida et al, 49,50) Uchida, 51,52) Uchida and Uchida. 53)…”

“…Using this angiomicroscope, foam cells in the disrupted plaque can be clearly discerned in patients. 37,38 a-2 [40][41][42][43]52) This technique may contribute to the understanding and evaluation of molecular targeted therapies of not only for coronary artery disease but also for aortic disease.…”