Arterial Wall Plaque Research Articles

Automated diagnosis of atherosclerosis using multi-layer ensemble models and bio-inspired optimization in intravascular ultrasound imaging.

Atherosclerosis causes heart disease by forming plaques in arterial walls. IVUS imaging provides a high-resolution cross-sectional view of coronary arteries and plaque morphology. Healthcare professionals diagnose and quantify atherosclerosis physically or using VH-IVUS software. Since manual or VH-IVUS software-based diagnosis is time-consuming, automated plaque characterization tools are essential for accurate atherosclerosis detection and classification. Recently, deep learning (DL) and computer vision (CV) approaches are promising tools for automatically classifying plaques on IVUS images. With this motivation, this manuscript proposes an automated atherosclerotic plaque classification method using a hybrid Ant Lion Optimizer with Deep Learning (AAPC-HALODL) technique on IVUS images. The AAPC-HALODL technique uses the faster regional convolutional neural network (Faster RCNN)-based segmentation approach to identify diseased regions in the IVUS images. Next, the ShuffleNet-v2 model generates a useful set of feature vectors from the segmented IVUS images, and its hyperparameters can be optimally selected by using the HALO technique. Finally, an average ensemble classification process comprising a stacked autoencoder (SAE) and deep extreme learning machine (DELM) model can be utilized. The MICCAI Challenge 2011 dataset was used for AAPC-HALODL simulation analysis. A detailed comparative study showed that the AAPC-HALODL approach outperformed other DL models with a maximum accuracy of 98.33%, precision of 97.87%, sensitivity of 98.33%, and F score of 98.10%.

Abstract 3070: Investigating CD36 Oligomerization In Macrophages

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Atherosclerosis, the main cause of CVD, results from the buildup of cholesterol-filled plaques in artery walls. Accumulation of cholesterol from oxidized low-density lipoprotein (oxLDL) leads to the formation of macrophage foam cells, a process that is mediated by CD36, a scavenger receptor that serves as the primary receptor for oxLDL. The structure of full-length CD36 has not been resolved, nor have the details or role of quaternary structure been fully elucidated. Studies have shown that CD36 has the ability to form homodimers and multimers in some cell types. However, the role of CD36 oligomerization in oxLDL uptake remains unknown. The goal of this study is to investigate CD36 oligomerization in macrophages, a cell type important in the initiation of atherosclerosis. We hypothesize that CD36 oligomerizes in macrophages to facilitate oxLDL uptake. To begin testing this hypothesis, we harvested elicited peritoneal macrophages from wild-type (WT) or CD36 knockout (CD36-KO) mice. We performed crosslinking experiments in which macrophages were incubated with BS3, a membrane-impermeable crosslinker, to stabilize CD36 oligomers. When crosslinked samples were separated by SDS-PAGE electrophoresis, we observed a decrease in monomeric species with increasing crosslinker concentration, however, BS3 also induced aggregation of CD36 rather than oligomer formation. We next turned to Native-PAGE electrophoresis, which lacks detergent entirely, to identify oligomeric species within macrophages, as well as PFO-PAGE electrophoresis, which contains a milder detergent than SDS. Both methods provided evidence of higher-order complexes in WT, but not in CD36-KO macrophages. To further validate our studies, we purified human full-length CD36 using an Sf9 insect cell system and demonstrated that pure CD36 forms homo-oligomers by PFO-PAGE. Together, these experiments provide strong evidence for CD36 oligomerization. Future studies will focus on correlating CD36 oligomerization with its functions in oxLDL binding and uptake. Understanding the higher-order structure of CD36 and how it impacts function will allow us to target CD36 to prevent foam cell formation and atherosclerosis.

Lessons from autopsy: Topographical variability of atherosclerosis plaques.

Atherosclerosis is a complex disease characterized by the accumulation of plaques in arterial walls. Understanding its pathogenesis remains incomplete, with factors like inflammation, oxidative stress, and hypertension playing critical roles. The disease exhibits preferential localization of plaques, with variability observed even within the same individual. Genetic, environmental, and lifestyle factors contribute to its heterogeneity. Histological plaque phenotypes vary widely, prompting classification schemes focusing on systemic and local factors deteriorating fibrous caps. Recent research highlights differences in plaque histology among arterial systems, suggesting unique pathophysiological mechanisms. This study reports on multiple atherosclerotic plaques detected at autopsy in various vascular sites of a single subject, emphasizing their histological diversity and underscoring the systemic nature of atherosclerosis.

Hypochlorous Acid and Chloramines Induce Specific Fragmentation and Cross-Linking of the G1-IGD-G2 Domains of Recombinant Human Aggrecan, and Inhibit ADAMTS1 Activity

Atherosclerosis is a chronic inflammatory disease and a leading cause of mortality. It is characterized by arterial wall plaques that contain high levels of cholesterol and other lipids and activated leukocytes covered by a fibrous cap of extracellular matrix (ECM). The ECM undergoes remodelling during atherogenesis, with increased expression of aggrecan, a proteoglycan that binds low-density-lipoproteins (LDL). Aggrecan levels are regulated by proteases, including a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1). Activated leukocytes release myeloperoxidase (MPO) extracellularly, where it binds to proteins and proteoglycans. Aggrecan may therefore mediate colocalization of MPO and LDL. MPO generates hypochlorous acid (HOCl) and chloramines (RNHCl species, from reaction of HOCl with amines on amino acids and proteins) that damage LDL and proteins, but effects on aggrecan have not been examined. The present study demonstrates that HOCl cleaves truncated (G1-IGD-G2) recombinant human aggrecan at specific sites within the IGD domain, with these being different from those induced by ADAMTS1 which also cleaves within this region. Irreversible protein cross-links are also formed dose-dependently. These effects are limited by the HOCl scavenger methionine. Chloramines including those formed on amino acids, proteins, and ECM materials induce similar damage. HOCl and taurine chloramines inactivate ADAMTS1 consistent with a switch from proteolytic to oxidative aggrecan fragmentation. Evidence is also presented for colocalization of aggrecan and HOCl-generated epitopes in advanced human atherosclerotic plaques. Overall, these data show that HOCl and chloramines can induce specific modifications on aggrecan, and that these effects are distinct from those of ADAMTS1.

Purification and Analysis of Circulating Lipid Particles.

Lipid particles found in circulating extracellular fluids such as blood or lymph are essential for cellular homeostasis, metabolism and survival. Such particles provide essential lipids and fats which enable cells to synthesize new membranes and regulate different biochemical pathways. Imbalance in lipid particle metabolism can cause pathological states such as atherosclerosis. Here, elevated low-density lipoprotein (LDL) accumulation leads to fat-filled lesions or plaques in arterial walls. In this chapter, we provide a detailed set of protocols for the rapid and safe purification of lipid particles from human blood using high-speed ultracentrifugation. We provide a detailed set of assays for further analysis of the biochemical and cellular properties of these lipid particles. By combining these assays, we can better understand the complex roles of different lipid particles in normal physiology and disease pathology.

Characteristics of cerebral ischemic stroke based on moyamoya disease and atherosclerosis-associated intracranial arterial stenosis

To analyze the characteristics of acute ischemic stroke (AIS) resulting from moyamoya disease (MMD) and intracranial large artery atherosclerotic stenosis (LAS). This real-world case control study enrolled imaging-confirmed AIS patients owing to MMD or LAS hospitalized from January 2015 through September 2020 consecutively. The features of risk factors, peripheral blood, and imaging presentations were compared between the two cohorts. A total of 191 eligible patients entered into final analysis, including 70 cases with MMD stroke and 121 with LAS stroke. LAS stroke vs. MMD stroke, the ratios of hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia were higher in the former (65.3 vs.12.9%, 65.3% vs. 4.3%, 39.7% vs. 2.9%, and 43.8% vs.12.9%; all p < 0.01) as well as baseline plasma arachidonic acid (AA) and adenosine diphosphate (ADP)-stimulated maximum platelet aggregation rates (75.3% vs. 60.8% and 73.1% vs.64.9%, respectively, all p < 0.01), which were positively correlated with triglycerides and cholesterol levels, blood glucose, age, and platelet counts (all p < 0.01). Classical watershed infarction (WSI) accounted for 87.14% in MMD stroke and 40.49% in LAS stroke, respectively (p < 0.01). Almost all of the patients with LAS showed plaques in arterial walls on CTA maps and non-homogeneous thickening with irregular luminal narrowing on HRMRI, while plaques were seldom found in MMD besides homogeneous thickening with regular luminal narrowing. Differing from LAS stroke, MMD stroke mainly presents with WSI and does not feature with platelet hyper-aggregation and fragmentation of ulcer plaque. Whereby, focusing on perfusion improvement rather than antiplatelets and statins may be the predominant step in MMD-stroke correction.

A model of chronic inflammation in atherosclerosis

Atherosclerosis is a chronic progressive disease leading to the formation of atherosclerotic plaques in artery walls, narrowing its lumen. In this work, we present a mathematical model of atherosclerosis development for the concentrations of cells and cytokines of innate immunity. This system describes a chronic inflammatory response in the intima of an artery vessel wall. The stationary points and their stability for reduced kinetic systems of two and five ODEs are investigated. The relationship of the obtained results is analyzed, and their biological interpretation is given.

Comparison of non-contrast vessel wall imaging and 3-D time-of-flight MRA for atherosclerotic stenosis and plaque characterization within intracranial arteries

PurposeWe compared the ability of intracranial high-resolution vessel wall imaging (VWI) without gadolinium and 3-D time-of-flight (3D-TOF) MRA techniques to characterize intracranial arterial stenosis and arterial wall plaque consistent with atherosclerotic plaque. MethodsConsecutive intracranial VWI examinations performed within 2 months of a 3D-TOF exam with at least 1 noted plaque was included. Examinations assessed 17 vessel segments for plaque and diameters of stenotic and normal segments using double oblique reformatted images. Results were compared with the VWI and 3D-TOF exams considered the reference standard for plaque and luminal stenosis, respectively. ResultsAssessed segments totaled 286 from 17 patients. Proximal segment sensitivity and specificity for luminal stenosis detection with VWI was 92.5% and 82.1%, respectively, whereas for assessing plaque with 3D-TOF it was 59.4% and 98.3%, respectively. The mean intra-rater difference in luminal diameter measurements between VWI and 3D-TOF at normal segments and at the area of maximal stenosis was 0.02mm (SD 0.51mm) and 0.08mm (SD 0.66mm), respectively. ConclusionsIntracranial VWI demonstrated reasonably high sensitivity and specificity for luminal stenosis assessment using 3D-TOF as a reference standard, while 3D-TOF demonstrated low sensitivity for plaque detection. Our results suggest that VWI can be used for simultaneous assessment of luminal stenosis and plaque in the intracranial arteries.

A NEW APPROACH FOR CLASSIFICATION OF ATHEROSCLEROSIS OF COMMON CAROTID ARTERY FROM ULTRASOUND IMAGES

Background and objectives: The diagnosis of carotid atherosclerosis is of vital importance, as this cardiovascular disease may cause myocardial infarction. One-third of deaths in the world occur due to myocardial infarction, commonly known as heart attack. Atherosclerosis is deposition of plaque in artery wall. It could be detected from the features of intima-media complex of the artery wall. This study proposes a new classification approach to distinguish between symptomatic and asymptomatic plaques using non-invasive carotid B-mode ultrasound images. These two types of plaques have diverse impacts on human life. In the first condition, slowly plaque formation reaches life-threatening condition and the second condition is acute in nature. Hence treatment protocol is to be decided based on the type of plaque. Methods: To locate the intima-media-complex region, the images are segmented using snake-based segmentation algorithm. Several features are extracted using fixed size blocks selected from the segmented region using gray-level co-occurrence matrix. Finally classification is performed using support vector machine. Results: The performance shows improvement in accuracy using lesser number of features than previous works. The reduction in feature size is achieved by incorporating segmentation in the pre-processing stage. In the classifier, 10-fold cross-validation protocol is used for training and testing and an accuracy of 100% is obtained. Conclusion: This proposed technique could work as an adjunct tool in quick decision-making for cardiologists and radiologists.

Radiologic observation of the blood supply changes around the knee with osteoarthritis

To compare blood supply changes around the knee joint between normal and osteoarthritis knee. From June 2014 to June 2015, 30 patients with knee osteoarthritis and 30 healthy adults were recruited. In osteoarthritis group, there were 9 males and 21 females, with a mean age of (65.967±7.132) years old(ranged, 53 to 82 years old), and the mean arterial pressure was(93.462±7.633) mmHg. In control group, there were 9 males and 21 females, with a mean age of (62.867±6.356) years old(ranged, 50 to 75 years old), and the mean arterial pressure was (92.122±9.675) mmHg. Inspection methods included color ultrasonic and computed tomography angiography of lower limbs. The patients were observed with: (1)collateral circulation; (2)artery circuity; (3)artery malformation; (4)artery stenosis; (5)arterial wall plaque formation. Stenosis was divided into 5 levels: level 1 as no narrow, level 2 as mild stenosis (1% to 49%), level 3 as moderate stenosis (50% to 70%), level 4 as severe stenosis (70% to 99%), level 5 as total obstruction. Diameter and blood flow dynamics of popliteal artery, pretibial artery, and posterior tibia artery in two groups were measured and compared. The study was accomplished with complete data collection, none of the patients was eliminated, and there were no loss of follow up. There were 3 cases in OA group and 4 cases in control group with the formation of collateral circulation, and the difference had no statistically significance. There was none in OA group and 2 in control group with the formation of artery circuity, and the difference had no statistically significance. There were no cases in both groups with artery malformation. In OA group, there was mild in 14 cases, moderate in 7 cases, severe in 9 cases. In control group, there was no arterial stenosis in 9 cases, mild in 10 cases, moderate in 6 cases, severe in 4 cases, total obstruction in 1 case. The difference between two groups was statistically significant; artery stenosis in OA group was more severe than that of the control group. Artery plaque formed in 30 cases in OA group and in 20 cases in control group. The difference between two groups was statistically significant; the rate of artery plaque formation in OA group was obviously higher than that of control group. In OA group, plaque calcification rate was 100% while 63% in control group. Difference of pretibial artery diameter was statistically significant, pretibial artery diameter is larger in OA group. Difference of popliteal artery flow velocity was statistically significant; velocity was faster in OA group. Difference of the posterior tibial artery flow velocity was statistically significant; velocity was faster in OA group. The differences of the three arteries had no statistical significances in related to arterial flow. Local artery system changes with the onset of knee joint osteoarthritis. Main pathological changesof local blood vessels were stenosis and plaque formation, but the amount of local artery blood flow was roughly the same as the control group. Possible mechanism is that the local artery stenosis speed up the artery blood flow velocity, resulting local perfusion. The local tissue ischemia and hypoxia caused a series of pathological changes. It is better to improve local vascular lesions than to accelerate the blood flow velocity in clinical treatment. Further more, interventional therapy for vascular pathology will be a new trend of osteoarthritis treatment.

Porphyromonas gingivalis is the most abundant species detected in coronary and femoral arteries

ABSTRACTAn association between oral bacteria and atherosclerosis has been postulated. A limited number of studies have used 16S RNA gene sequencing-based metagenomics approaches to identify bacteria at the species level from atherosclerotic plaques in arterial walls. The objective of this study was to establish detailed oral microbiome profiles, at both genus and species level, of clinically healthy coronary and femoral artery tissues from patients with atherosclerosis. Tissue specimens were taken from clinically non-atherosclerotic areas of coronary or femoral arteries used for attachment of bypass grafts in 42 patients with atherosclerotic cardiovascular disease. Bacterial DNA was sequenced using the MiSeq platform, and sequence reads were screened in silico for nearly 600 oral species using the HOMINGS ProbeSeq species identification program. The number of sequence reads matched to species or genera were used for statistical analyses. A total of 230 and 118 species were detected in coronary and femoral arteries, respectively. Unidentified species detected by genus-specific probes consisted of 45 and 30 genera in coronary and in femoral artery tissues, respectively. Overall, 245 species belonging to 95 genera were detected in coronary and femoral arteries combined. The most abundant species were Porphyromonas gingivalis, Enterococcus faecalis, and Finegoldia magna based on species probes. Porphyromonas, Escherichia, Staphylococcus, Pseudomonas, and Streptococcus genera represented 88.5% mean relative abundance based on combined species and genus probe detections. Porphyromonas was significantly more abundant than Escherichia (i.e. 46.8% vs. 19.3%; p = 0.0005). This study provides insight into the presence and types of oral microbiome bacterial species found in clinically non-atherosclerotic arteries.

Lipid droplet-associated proteins in atherosclerosis (Review).

Accumulation of atherosclerotic plaques in arterial walls leads to major cardiovascular diseases and stroke. Macrophages/foam cells are central components of atherosclerotic plaques, which populate the arterial wall in order to remove harmful modified low-density lipoprotein (LDL) particles, resulting in the accumulation of lipids, mostly LDL-derived cholesterol ester, in cytosolic lipid droplets (LDs). At present, LDs are recognized as dynamic organelles that govern cellular metabolic processes. LDs consist of an inner core of neutral lipids surrounded by a monolayer of phospholipids and free cholesterol, and contain LD-associated proteins (LDAPs) that regulate LD functions. Foam cells are characterized by an aberrant accumulation of cytosolic LDs, and are considered a hallmark of atherosclerotic lesions through all stages of development. Previous studies have investigated the mechanisms underlying foam cell formation, aiming to discover therapeutic strategies that target foam cells and intervene against atherosclerosis. It is well established that LDAPs have a major role in the pathogenesis of metabolic diseases caused by dysfunction of lipid metabolism, and several studies have linked LDAPs to the development of atherosclerosis. In this review, several foam cell-targeting pathways have been described, with an emphasis on the role of LDAPs in cholesterol mobilization from macrophages. In addition, the potential of LDAPs as therapeutic targets to prevent the progression and/or facilitate the regression of the disease has been discussed.

Human umbilical vein endothelial cells promote the inhibitory activation of CD4+CD25+Foxp3+ regulatory T cells via PD-L1

BackgroundAtherosclerosis (AS) is a chronic inflammation characterized by massive infiltration of inflammatory cells in arterial wall plaques. Programmed death ligand-1 (PD-L1), a co-stimulatory molecule, plays a vital role in regulating immune responses. We investigated the role and mechanisms of PD-L1 expressed on oxidized low-density lipoprotein (ox-LDL)-impaired human umbilical vein endothelial cells (HUVECs) in promoting activation and cytokine production of CD4+CD25+ forkhead box P3 (FoxP3) regulatory T cells (Tregs). Methods and resultsTregs were incubated alone, with HUVECs or HUVECs pre-stimulated with ox-LDL in the presence of anti-CD3 monoclonal antibodies (mAbs) for 48 h. HUVECs were shown to upregulate the immune phenotypic markers of Tregs, such as glucocorticoid-induced TNF receptor (GITR), cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 protein (PD-1). Moreover, HUVECs modulated cytokine production of Tregs (e.g., interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1)). HUVECs treated with anti-PD-L1 mAbs were unable to regulate the surface expression and cytokine production of Tregs. The Transwell culture system suggested that interaction between HUVECs and Tregs via PD-L1 requires cell-to-cell contact. ConclusionExpression of the negative co-stimulatory molecule PD-L1 on HUVECs may upregulate the inhibitory activation and cytokine production of CD4+CD25+Foxp3+ regulatory T cells in AS.

Sugar-based amphiphilic nanoparticles arrest atherosclerosis in vivo

Atherosclerosis, the build-up of occlusive, lipid-rich plaques in arterial walls, is a focal trigger of chronic coronary, intracranial, and peripheral arterial diseases, which together account for the leading causes of death worldwide. Although the directed treatment of atherosclerotic plaques remains elusive, macrophages are a natural target for new interventions because they are recruited to lipid-rich lesions, actively internalize modified lipids, and convert to foam cells with diseased phenotypes. In this work, we present a nanomedicine platform to counteract plaque development based on two building blocks: first, at the single macrophage level, sugar-based amphiphilic macromolecules (AMs) were designed to competitively block oxidized lipid uptake via scavenger receptors on macrophages; second, for sustained lesion-level intervention, AMs were fabricated into serum-stable core/shell nanoparticles (NPs) to rapidly associate with plaques and inhibit disease progression in vivo. An AM library was designed and fabricated into NP compositions that showed high binding and down-regulation of both MSR1 and CD36 scavenger receptors, yielding minimal accumulation of oxidized lipids. When intravenously administered to a mouse model of cardiovascular disease, these AM NPs showed a pronounced increase in lesion association compared with the control nanoparticles, causing a significant reduction in neointimal hyperplasia, lipid burden, cholesterol clefts, and overall plaque occlusion. Thus, synthetic macromolecules configured as NPs are not only effectively mobilized to lipid-rich lesions but can also be deployed to counteract atheroinflammatory vascular diseases, highlighting the promise of nanomedicines for hyperlipidemic and metabolic syndromes.

Segmentation of Intima Media Complex ofCommon Carotid Artery

Atherosclerosis is a disease of blood vessels caused by the formation of plaques in artery walls. Its diagnosis is one of the most important medical examinations for the prevention of cardiovascular events, like myocardial infarction and stroke. The segmentation of the intima-media complex (IMC) of the common carotid artery (CCA) wall is important for the evaluation of the intima media thickness (IMT) on B-mode ultrasound (US) images. IMT is considered an important marker in the evaluation of the risk for the development of atherosclerosis. Carotid intima media thickness (IMT), which is the distance between the lumen-intima and the media-adventitia interfaces, is a measure of early atherosclerosis. segmentation algorithm is based on active contours and active contours without edges and provides information to achieve accurate segmentation. The level set formulation by Chan and Vese model provides a segmentation of the CCA US images into different distinct regions, one of which corresponds to the carotid wall region below the lumen and includes the far wall IMC.

OTC Antioxidant Products for the Treatment of Cardiovascular and other Disorders: Popular Myth or Fact?

Cardiovascular disease (CVD) is the number one cause of mortality worldwide as reported by World Health Organization (WHO), Centers for Disease Control (CDC) and American Heart Association (AHA). The role of micronutrients has been studied extensively as CVD risk minimizing intervention. Among these, dietary supplements antioxidants available over the counter are highly commercialized but scientific evidences and clinical trials supporting their use is not conclusive yet [1]. The beneficial effects of these antioxidants are focused mainly against pathogenesis of atherosclerosis, as the primary contributor to coronary artery disease and resulting cardiovascular complications. Atherosclerosis is chronic inflammatory process of deposition of fatty cholesterol filled plaque in arterial wall which narrows the diameter and obstructs blood flow down the length of coronary artery and throughout its branches. Hyperlipidemia (high HDL: LDL ratio), high blood pressure, toxins from tobacco are assumed to be the major risk factor of atherosclerosis. If plasma LDL exceeds the regulatory capacity of endothelial cells, LDL crosses the endothelial barrier and trapped in sub-endothelial space where they are susceptible for oxidation by reactive oxygen species (ROS) - superoxide anion (·O2−), hydroxyl radical (OH·), hydrogen peroxide (H2O2), reactive nitrogen species (RNS), nitric oxide (NO) and peroxynitrite (ONOO·) released by endothelial cells and macrophages [2]. These modified LDL stimulates endothelial cells to express various cell adhesion molecules (VCAM-I, P-selectin etc.) and chemotactic factors (monocyte chemotactic factor-1, MCP-1) for the recruitment of monocytes. Monocyte attachment is initiated by P-selectin on endothelial cell upon binding with P-selectin glycoprotein ligand-1 (PSGL-1) on the monocytes leading to rolling and prolonging the contact of monocyte on the arterial wall and initiate diapedesis across endothelial layers. Monocytes differentiate into macrophages under the influence of monocyte colony stimulating factor (M-CSF). Oxidized LDL is then engulfed in an unregulated fashion by macrophage scavenger receptor resulting in intracellular accumulation of cholesterol and forms foam cell formation [3,4]. Macrophages are also involved in activation of T cells to amplify the inflammatory response by secreting TNF-α and INF-γ. Finally, smooth muscle cells proliferate and migrate from tunica media and shield the fatty plaque and synthesize collagen to form a fibrous cap [5–7].

Is it time to revise the HDL cholesterol hypothesis?

Formation of plaques in artery walls, or atherogenesis, is known to lead to cardiovascular disease risk and heart disease. Low-density lipoproteins (LDLs), which deliver cholesterol to inflammatory cells in blood vessels, are linked to disease, which is commonly managed using cholesterol-lowering therapies. Whether increasing levels of high-density lipoproteins (HDLs), which remove cholesterol from the circulation, can be cardioprotective has not been clear, despite early clinical studies showing evidence for a positive effect in cardiovascular disease. In 'Bench to Bedside', Daniel J. Rader and Alan R. Tall discuss how the field should focus on promoting reverse cholesterol transport that would result in cholesterol efflux from macrophages to biliary excretion rather than simply trying to increase HDL cholesterol levels. Understanding how different molecular mechanisms operate in this 'HDL flux hypothesis' will uncover ways to develop HDL-targeted therapeutics that will protect from cardiovascular and heart disease. In 'Bedside to Bench', Jay W. Heinecke peruses clinical studies to propose better and simpler ways to measure reverse cholesterol transport in the clinic. Genetic alterations and factors involved in HDL functionality may be useful for quantifying HDL function and finding effective drugs to lower cardiovascular disease risk.

Exacerbation of Susac Syndrome Retinopathy by Interferon Beta-1a

Susac syndrome features the triad of multiple branch retinal artery occlusions, hearing loss due to microinfarctions of the cochlea, and encephalopathy due to brain microangiopathy.1 Initial misdiagnosis as multiple sclerosis (MS) is not uncommon.1,2 Magnetic resonance imaging evidence of microinfarctions of the corpus callosum and multiple yellow retinal arterial wall plaques on fundus examination are helpful in differentiating this condition from demyelinating diseases.2,3

Retinal and Optic Nerve Head Pathology in Susac's Syndrome

This article describes the first retinal histopathologic findings in a patient with Susac's syndrome (SS). Observational case report. A 51-year-old white woman diagnosed with SS. Eyes from a 51-year-old white woman diagnosed with SS were obtained at autopsy. One retina was dissected and processed for adenosine diphosphatase (ADPase) flat embedding. Selected areas were processed further for transmission electron microscopy. Histopathologic examination using ADPase flat-embedding technique. There were vaso-occlusive changes in the retinal periphery resulting in small areas of capillary dropout. Cross-sections demonstrated serous filled spaces between the retinal blood vessels and the internal limiting membrane. Lumens adjacent to these spaces appeared compressed and sometimes closed, but without thrombosis. Decreased ADPase activity in some peripheral blood vessels suggested endothelial cell dysfunction and vaso-occlusion. In the optic nerve head, numerous corpora amylacea were observed in the vicinity of capillaries with thickened walls and narrow lumens. Transmission electron microscopy demonstrated thickened and amorphous vascular basal lamina and open endothelial cell junctions in some retinal blood vessels. The serous deposits with compression of retinal vessel lumens observed histologically probably represent the so-called string of pearls described clinically in SS. Chronic extension of these serous deposits along the vessel wall possibly are the cause of retinal arterial wall plaques as described by Gass and other investigators. In the optic nerve head, corpora amylacea are probably a result of microinfarcts resulting from optic nerve head capillary angiopathy. Accumulation of amorphous material in the basal lamina, loss of viable endothelial cells, and capillary dropout suggest that SS may be an endotheliopathy.

Relationship between the enhanced intensity of carotid plaques in contrast-enhanced ultrasonography and the risk of cerebral infarction

Objective To assess the relationship between the enhanced intensity of carotid plaque and risk of cerebral infarction using contrast-enhanced ultrasonography(CEUS). Methods Eighty one patients with cerebral infarction and 95 patients without cerebral infarction were enrolled in this study. All the patients were performed using CEUS. The characteristics of plaque enhancement was categorized: grade Ⅰ , non-enhancement;grade Ⅱ , the arterial wall vasa vasorum enhancement; grade Ⅲ. the arterial wall vasa vasorum and plaque shoulder enhancement; grade Ⅳ , extensive and internal plaque enhancement. The data between the two groups was compared and analysed. Results Plaque enhancement presented with grade Ⅰ in 7 cases of 81 patients and 26 cases of 95 controls,grade Ⅱ in 14 and 37,grade Ⅲ in 26 and 17,grade Ⅳ in 34 and 15. The percentage of stroke in grade Ⅰ was 21.2% (7/33),grade Ⅱ was 27.5%(14/51), grade Ⅲ was 60.5% (26/43) and grade Ⅳ was 69.4% (34/49). The percentage of stroke in grade Ⅲ was significantly higher than that in grade Ⅰ and Ⅱ ( P = 0. 001, P = 0. 001 ), and there was no significant difference between grade Ⅲ and Ⅳ ( P = 0.370). The sensitivity and specificity for grade of plaque enhancement (AUC = 0. 721, cutoff value > grade Ⅱ ) were 74. 1 % and 66. 3% respectively. Conclusions The grade of enhancement of carotid plaques in CEUS is a valid indicator to anticipate cerebral infarction. The higher the grade of enhancement of carotid plaques,the higher the risk of cerebral infarction. Key words: Ultrasonography; Microbubbles; Brain infarction; Carotid stenosis