Mechanism of ceroid formation in atherosclerotic plaque: in situ studies using a combination of Raman and fluorescence spectroscopy

Abstract

Abstract. Accumulation of the lipid-protein complex ceroid is a characteristic of atherosclerotic plaque. The mechanism of ceroid formation has been extensively studied, because the complex is postulated to contribute to plaque irreversibility. Despite intensive research, ceroid deposits are defined through their fluorescence and histochemical staining properties, while their composition remains unknown. Using Raman and fluorescence spectral microscopy, we examine the composition of ceroid in situ in aorta and coronary artery plaque. The synergy of these two types of spectroscopy allows for identification of ceroid via its fluorescence signature and elucidation of its chemical composition through the acquisition of a Raman spectrum. In accordance with in vitro predictions, low density lipoprotein (LDL) appears within the deposits primarily in its peroxidized form. The main forms of modified LDL detected in both coronary artery and aortic plaques are peroxidation products from the Fenton reaction and myeloperoxidase-hypochlorite pathway. These two peroxidation products occur in similar concentrations within the deposits and represent ∼40 and 30% of the total LDL (native and peroxidized) in the aorta and coronary artery deposits, respectively. To our knowledge, this study is the first to successfully employ Raman spectroscopy to unravel a metabolic pathway involved in disease pathogenesis: the formation of ceroid in atherosclerotic plaque. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

Clinical Characterization of Coronary Atherosclerosis With Dual-Modality OCT and Near-Infrared Autofluorescence Imaging

“…Based on the findings of this study and information gleaned from the literature (21,22), various hypotheses can be made about the potential sources of NIRAF in atherosclerotic plaques and its potential relationship to coronary wall inflammation. NIRAF in atherosclerotic plaque may arise from the modification of lipids and lipoproteins by oxidative stress (21,22).…”

“…Based on the findings of this study and information gleaned from the literature (21,22), various hypotheses can be made about the potential sources of NIRAF in atherosclerotic plaques and its potential relationship to coronary wall inflammation. NIRAF in atherosclerotic plaque may arise from the modification of lipids and lipoproteins by oxidative stress (21,22). Studies have shown that ceroid, a protein-lipid oxidation byproduct found in atherosclerotic plaque, has a yellow fluorescence spectrum (22) and it is possible that the tail of ceroid's fluorescence emission may extend into the NIR.…”

Pathology of human plaque vulnerability: Mechanisms and consequences of intraplaque haemorrhages

“…Sudanophilic ceroids could be also stained by Oil Red O on deparaffinised sections, providing evidence of lipid entrapment in insoluble bodies. Ceroids can colocalize with iron deposits within cells and tissue [49] and the presence of Fenton-dependent and myeloperoxidasedependent LDL peroxidation products, free cholesterol and cholesteryl esthers, haemoglobin and collagen has been recently identified in ceroids by Raman and fluorescence spectroscopy [50] suggesting that the different components of RBC are involved in ceroid genesis. Ceroids can remain present within the tissue, even when other RBC signatures have partly or completely disappeared.…”

Behavior of the thermal diffusivity of native and oxidized human low-density lipoprotein solutions studied by the Z-scan technique

“…3,4 Furthermore, studies have shown that atherosclerosis is associated with higher concentrations of modified LDL (moLDL) in the bloodstream. 5,6 Recently, Haka et al 7 used a combination of Raman and fluorescence spectroscopies to investigate the atherosclerotic plaque formation.…”