Atherothrombosis: Epidemiology, Pathophysiology, and Prevention

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).

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“…1 Atherosclerosis was once viewed primarily as a lipid disorder. Recently, it has come to be viewed more as an inflammatory disease.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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“…The disease starts as an endothelial dysfunction, which initiates recruitment of inflammatory cells and lipids within the arterial wall [1]. This, together with smooth muscle hyperplasia, leads to the development of slowly growing atherosclerotic plaques that become clinically symptomatic when they cause significant haemodynamic stenosis.…”

Section: Introductionmentioning

confidence: 99%

Anatomical-based model for simulation of HIFU-induced lesions in atherosclerotic plaques

Almekkaway

Shehata

Ebbini

2015

International Journal of Hyperthermia

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Purpose: The aim of this study was to simulate the effect of high intensity focused ultrasound (HIFU) in non-homogenous medium for targeting atherosclerotic plaques in vivo. Materials and methods: A finite-difference time-domain heterogeneous model for acoustic and thermal tissue response in the treatment region was derived from ultrasound images of the treatment region. A 3.5 MHz dual mode ultrasound array suitable for targeting peripheral vessels was used. The array has a lateral and elevation focus at 40 mm with fenestration in its centre through which a 7.5 MHz diagnostic transducer can be placed. Two cases were simulated where seven adjacent HIFU shots ($5000 W/cm 2 , 2-s exposure time) were targeted on the plaque tissue within the femoral artery. The transient bioheat equation with a convective term to account for blood flow was used to predict the thermal dose. The results of the simulation model were then validated against the histology data. Results: The simulation model predicted the HIFU-induced damage for both cases, and correlated well with the histology data. For the first case thermal damage was detected within the targeted plaque, while for the second case thermal damage was detected in the pre-focal region. Conclusion: The results suggest that a realistic, image-based acoustic and thermal model of the treatment region is capable of predicting the extent of thermal damage to target plaque tissue. The model considered the effect of the wall thickness of large arteries and the heat-sink effect of flowing blood. The model is used for predicting the size and pattern of HIFU damage in vivo.

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“…2,3 The underlying CI pathology involves the formation of a thrombus over an unstable atherosclerotic plaque. 4 Smooth muscle cells (SMCs) are well-accepted players in the evolution of atherosclerotic plaque in addition to participating in the establishment of conditions that facilitate plaque rupture and/or thrombus formation via several activities, including vasospasm and synthesis of extracellular matrix components or proteolytic enzymes. Remodeling and deformation of the intima through tensile force generation by SMCs might also be instrumental in this plaque rupture process.…”

Section: Introductionmentioning

confidence: 99%

Association of the smoothelin (SMTN) gene with cerebral infarction in men: A haplotype-based case–control study

et al. 2012

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Smoothelin is a specific type of cytoskeletal protein found in smooth muscle cells (SMCs). Several previous research studies have examined the relationship between smoothelin and atherosclerotic plaque. The aim of the present study was to further assess the association between the human SMTN gene and cerebral infarction (CI) using a haplotypebased case-control study. A total of 168 CI patients and 259 supercontrols were genotyped for the five single-nucleotide polymorphisms (SNPs) used as genetic markers for the human SMTN gene (rs2074738, rs5997872, rs56095120, rs9621187 and rs10304). Data were analyzed for three separate groups that included total subjects, men and women. The genotypic distribution of rs10304 for men showed a significant difference between the control and CI groups. In addition, the frequency of the C-T-T-A haplotype (established by rs5997872, rs56095120, rs9621187 and rs10304) was significantly higher in the CI versus the control group (p = 0.013), while the frequency of the C-A-T-G haplotype (established by rs5997872, rs56095120, rs9621187 and rs10304) in the CI group was significantly lower than that seen in the controls (p = 0.021). In conclusion, we confirmed that the haplotype constructed using rs5997872, rs56095120, rs9621187 and rs10304 was a useful genetic marker of CI in Japanese men.

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Atherothrombosis: Epidemiology, Pathophysiology, and Prevention

Cited by 64 publications

References 75 publications

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

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

Anatomical-based model for simulation of HIFU-induced lesions in atherosclerotic plaques

Association of the smoothelin (SMTN) gene with cerebral infarction in men: A haplotype-based case–control study

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