Early Plaque Research Articles

Ultrasound imaging for risk assessment in atherosclerosis.

Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall; (c) assessing plaque neovascularization and (d) imaging the expression of disease-relevant molecules using molecular imaging.

Veins in plaques of multiple sclerosis patients – a longitudinal magnetic resonance imaging study at 7 Tesla –

To monitor the venous volumes in plaques of patients with multiple sclerosis (MS) compared to an age-matched control group over a period of 3.5 years. Ten MS patients underwent an annual neurological examination and MRI. Susceptibility-weighted imaging (SWI) combined with fluid-attenuated inversion recovery (FLAIR) or FLAIR-like contrast at 7 Tesla (7 T) magnetic resonance imaging (MRI) was used for manual segmentation of veins in plaques, in the normal-appearing white matter (NAWM) and in location-matched white matter of 9 age-matched controls. Venous volume to tissue volume ratio was assessed for each time point in order to describe the dynamics of venous volumes in MS plaques over time. MS plaques, which were newly detected during the study period, showed significantly higher venous volumes compared to the preplaque area 1 year before plaque detection and the corresponding NAWM regions. Venous volumes in established MS plaques, which were present already in the first scans, were significantly higher compared to the NAWM and controls. Our data underpin a relation of veins and plaque development in MS and reflect increased apparent venous calibers due to increased venous diameters or increased oxygen consumption in early MS plaques. • Longitudinal 7 T Magnetic Resonance Imaging study of intralesional veins in MS patients. • Venous volumes are significantly increased in newly detected and established MS plaques. • Venous volumes in established MS plaques show a trend to decrease with time.

Loss of p27 phosphorylation at Ser10 accelerates early atherogenesis by promoting leukocyte recruitment via RhoA/ROCK

Reduced phosphorylation of the tumor suppressor p27Kip1 (p27) at serine 10 (Ser10) is a hallmark of advanced human and mouse atherosclerosis. Apolipoprotein E-null mice defective for this posttranslational modification (apoE−/−p27Ser10Ala) exhibited increased atherosclerosis burden at late disease states. Here, we investigated the regulation of p27 phosphorylation in Ser10 at the very initial stages of atherosclerosis and its impact on endothelial-leukocyte interaction and early plaque formation. Hypercholesterolemia in fat-fed apoE−/− mice is associated with a rapid downregulation of p27-phospho-Ser10 in primary endothelial cells (ECs) and in aorta prior to the development of macroscopically-visible lesions. We find that lack of p27 phosphorylation at Ser10 enhances the expression of adhesion molecules in aorta of apoE−/− mice and ECs, and augments endothelial-leukocyte interactions and leukocyte recruitment in vivo. These effects correlated with increased RhoA/Rho-associated coiled-coil containing protein kinase (ROCK) signaling in ECs, and inhibition of this pathway with fasudil reduced leukocyte-EC interactions to control levels in the microvasculature of p27Ser10Ala mice. Moreover, apoE−/−p27Ser10Ala mice displayed increased leukocyte recruitment and homing to atherosusceptible arteries and augmented early plaque development, which could be blunted with fasudil. In conclusion, our studies demonstrate a very rapid reduction in p27-phospho-Ser10 levels at the onset of atherogenesis, which contributes to early plaque build-up through RhoA/ROCK-induced integrin expression in ECs and enhanced leukocyte recruitment.

The shape of middle cerebral artery and plaque location: high-resolution MRI finding.

The location of plaque may be associated with the vascular geometry. We aimed to examine the relationship between the geometry of middle cerebral artery and the plaque location detected by high-resolution magnetic resonance imaging. Among patients with a single subcortical infarction without a significant middle cerebral artery stenosis on magnetic resonance angiography, those with a plaque detected from high-resolution magnetic resonance imaging were prospectively enrolled. The shape of middle cerebral artery was measured from the coronal view, and was classified as straight, U-shaped, inverted U-shaped, and S-shaped. The location of the plaque was divided into superior and inferior, and analyzed according to the shape of middle cerebral artery. Among the 40 patients, the shape of middle cerebral artery was straight in 7 (17·5%), U-shaped in 10 (15·0%), inverted U-shaped in 11 (27·5%), and S-shaped in 12 patients (30·0%). The superior plaque was more closely associated with straight (85·7%) or U-shaped middle cerebral arteries (90·0%), whereas inverted U-shaped (81·8%) and S-shaped middle cerebral arteries (75·0%) were more often associated with inferior plaque. The prevalence of symptomatic plaque was higher in superior than inferior plaques (70·0% vs. 25·0%, P = 0·004). Multivariate analysis showed that straight and U-shaped middle cerebral artery was the only significant factor associated with the superior plaque. The shape of middle cerebral artery may be a factor determining the location of early atherosclerotic plaque.

Endogenous activated angiotensin-(1-7) plays a protective effect against atherosclerotic plaques unstability in high fat diet fed ApoE knockout mice

Background and objectiveWe recently found that exogenous angiotensin-(1-7) [Ang-(1-7)] inhibits Angiotensin II (Ang-II)-induced atherosclerotic lesion formation and enhances plaque stability. Our objective was to evaluate the role of endogenous activated Ang-(1-7) during atherosclerosis. Methods and resultsIn mice, the effects of endogenous Ang-(1-7) on atherogenesis in early stage and plaque stability in late stage were observed in ApoE knockout (ApoE−/−) mice fed with a high fat diet. Blockage of endogenous Ang-(1-7) with A779, an Ang-(1-7) antagonist, did not increase early plaque lesion formation, however, it remarkably enhanced contents of lipids and macrophages and decreased contents of vascular smooth muscle cells (VSMCs) and collagens in late lesions. The expressions of proinflammatory cytokines, and the expressions and activities of matrix metalloproteinases were significantly elevated in A779-treated group than those in vehicle-treated group in late lesions. Exogenous Ang-(1-7) treatment attenuated early atherosclerotic plaque formation and enhanced late plaques stability in this model. The contents of Ang-II and Ang-(1-7) and activity of ACE2 in late atherosclerotic plaques were higher than those of early atherosclerotic lesions. ConclusionEndogenous activated Ang-(1-7) enhanced late atherosclerotic plaques stability but did not affect early atherosclerotic plaque formation. Therapies to elevate endogenous Ang-(1-7) may be a potentially effective approach to attenuate atherosclerotic plaques vulnerability.

Clinical Review of Current Techniques of Magnetic Resonance Imaging of Atherosclerosis

Cardiovascular disease (CVD), notably atherosclerosis, is the leading cause of morbidity and mortality worldwide, commonly caused by thrombotic occlusion of a vulnerable plaque. Early assessment of atherosclerotic lesions is an important diagnostic goal in order to decrease the coronary artery siases burden. The purpose of this article is to review current MRI techniques on atherosclerosis and explore their clinical applications. First, this article will review the pathogenesis of atherosclerosis and describe various vulnerable plaque features i.e. intraplaque hemorrhage, lipid rich necrotic core, thin fibrous caps, neovascularization, and plaque inflammation. A comparison of different noninvasive in vivo imaging of atherosclerosis, specifically ultrasound, computer tomography, and magnetic resonance imaging will be discussed. This article will argue that MRI is best suited for detecting early plaque lesions. Next, the current MR imaging techniques in atherosclerosis will be introduced. Then this article will examine the clinical impact of MRI on atherosclerotic burden based on their vascular location. Lastly, new strategies in MRI imaging of atherosclerosis will be revealed.

MRI, the technology for imaging of thrombi and inflammation.

Atherosclerosis and its sequelae have a major impact on morbidity and mortality. The rupture of an inflamed atherosclerotic plaque is a crucial event, since it can result in acute thrombotic closure of an arterial vessel, resulting e. g. in myocardial infarction or stroke. Not only detection of early plaque rupture with imminent closure is therefore of clinical interest, but also timely detection of vascular inflammation and atherosclerotic plaque progression. However, plaque inflammation or even plaque rupture without vessel occlusion is not reliably detectable by current imaging techniques. Coronary angiography is the gold standard for evaluation of the coronary vessels, but only allows visualization of the vessel lumen without characterizing the important pathophysiology of the vessel wall. Therefore, highly inflamed and rupture prone plaques can be missed, or appear as a minor vessel narrowing. Although currently available techniques such as intravascular ultrasound or optical coherence tomography allow a further characterization of atherosclerotic plaques, it would be desirable to detect plaque inflammation, early plaque rupture or vascular thrombosis by non-invasive techniques such as magnetic resonance imaging (MRI), since they could allow early identification of patients at risk or triage of symptomatic patients. In this manuscript, different strategies for detection of vascular inflammation, plaque-rupture and thrombosis by MRI will be discussed, with a special focus on molecular imaging contrast agents.

Hypertrophic lichen sclerosus sine sclerosis: clues to histopathologic diagnosis when presenting as psoriasiform lichenoid dermatitis.

The histopathologic diagnosis of lichen sclerosus (LS) is usually facilitated by a subepidermal zone of sclerosis. In the absence of sclerosis, LS mostly presents itself as a psoriasiform lichenoid dermatitis that may be difficult to distinguish from other diseases. We sought to assess histopathologic findings that allow recognition of LS in the absence of sclerosis. We studied 28 criteria in 100 biopsy specimens of LS from genital or perianal skin, including 55 cases with marked sclerosis, 16 cases with mild sclerosis confined to foci of the papillary dermis and 29 cases without sclerosis. Fifteen cases each of the early plaque stage of mycosis fungoides, lichen planus and lichen simplex chronicus were studied for comparison. Some histopathologic hallmarks of LS were seen chiefly in sclerotic lesions and, therefore, did not contribute to the diagnosis of difficult cases, such as dissolution of elastic fibers. Others were seen rarely in non-sclerotic lesions but might be helpful in individual cases, including follicular hyperkeratosis and thickening of the basement membrane. Findings that were more common and may be utilized as clues to the histopathologic diagnosis of non-sclerotic LS include tiny foci of homogenized tissue in dermal papillae, marked fibrosis with thickening of the papillary dermis, marked thickening of individual collagen fibers, lymphocytes aligned in rows between those fibers, necrotic keratinocytes, often with preserved pyknotic nuclei, in all reaches of the epidermis, including the cornified layer, clustering of necrotic keratinocytes above elongated dermal papillae and vertical columns of parakeratosis with distinct dyskeratotic parakeratotic cells. In the absence of sclerosis, histopathologic diagnosis of LS depends on findings that are less distinctive. Nonetheless, a constellation of those findings allows a specific diagnosis to be made.

Vulnerable Carotid Artery Plaque Evaluation: Detection Agreement between Advanced Ultrasound, Computed Tomography, and Magnetic Resonance Imaging: A Phantom Study

PurposeImaging plaque morphology, in addition to luminal grading, may improve stroke risk-management by identifying structural atherosclerotic plaques alterations responsible for cerebrovascular events. The purpose of this study was to evaluate the agreement between our enhanced ultrasound (US) imaging method and high-resolution cross-sectional imaging modalities, such as multidetector-row computed tomography (CT) and magnetic resonance imaging (MRI), in the characterization of vulnerable plaques. MethodsSixty tissue-like phantoms were created to simulate various types of diseased plaque segments. We prospectively assessed each sample with US, CT, and MRI. Plaque characteristics considered included surface irregularity, ulceration, fissure, and presence of internal fluid core(s). We evaluated the agreement between and among the three modalities, as well as the accuracy of each compared with the true pathology. ResultsThere was moderate to substantial agreement among the three modalities in the detection of morphologic characteristics. There was no significant difference in accuracy between US and CT in the presence of ulceration(s) (P = .23), lucency (P = .23), or fissures (P = .07); however, US was significantly more accurate than MRI for each of these characteristics (P = .0001, P = .0001, P = .02, respectively). None of the three modalities did display any significant difference in accuracy in the identification of irregular surface. There was substantial agreement among the three radiologists (intraclass correlation coefficient, 0.61; 95% confidence interval, 0.46–0.74) in their assessment of plaque subtype, ranging from 80%–85% accuracy in identifying the plaque subtypes for each classification. ConclusionsEnhanced plaque imaging can identify potentially significant plaque characteristics and provide insight into early causative conditions of carotid atherosclerosis. Our results suggest that the types of plaque pathologies derived from our US method showed good agreement with CT and surpass information gathered on MRI. This imaging protocol could potentially shift the paradigm in early carotid plaque imaging likely to predict the onset of vulnerable plaques, thus improving preventative management of atherosclerosis.

Early canine plaque biofilms: characterization of key bacterial interactions involved in initial colonization of enamel.

Periodontal disease (PD) is a significant problem in dogs affecting between 44% and 63.6% of the population. The main etiological agent for PD is plaque, a microbial biofilm that colonizes teeth and causes inflammation of the gingiva. Understanding how this biofilm initiates on the tooth surface is of central importance in developing interventions against PD. Although the stages of plaque development on human teeth have been well characterized little is known about how canine plaque develops. Recent studies of the canine oral microbiome have revealed distinct differences between the canine and human oral environments and the bacterial communities they support, particularly with respect to healthy plaque. These differences mean knowledge about the nature of plaque formation in humans may not be directly translatable to dogs. The aim of this study was to identify the bacterial species important in the early stages of canine plaque formation in vivo and then use isolates of these species in a laboratory biofilm model to develop an understanding of the sequential processes which take place during the initial colonization of enamel. Supra-gingival plaque samples were collected from 12 dogs at 24 and 48 hour time points following a full mouth descale and polish. Pyrosequencing of the 16S rDNA identified 134 operational taxonomic units after statistical analysis. The species with the highest relative abundance were Bergeyella zoohelcum, Neisseria shayeganii and a Moraxella species. Streptococcal species, which tend to dominate early human plaque biofilms, had very low relative abundance. In vitro testing of biofilm formation identified five primary colonizer species, three of which belonged to the genus Neisseria. Using these pioneer bacteria as a starting point, viable two and three species communities were developed. Combining in vivo and in vitro data has led us to construct novel models of how the early canine plaque biofilm develops.

Abstract 15768: Mitochondria-Targeted DNA Repair Glycosylase Ogg1 Suppresses Early Stage of Atherogenesis in Ogg1 Deficient Mice

Introduction: Reactive oxygen species (ROS) play a key role in the development of atherosclerosis. Mitochondria are a main source of endogenous ROS in the cell. Mitochondrial DNA (mtDNA) is sensitive to oxidation and our previous results from cultured cell and intact animal models suggest that increasing mtDNA repair prevents both oxidative mtDNA damage and associated cytotoxicity and cellular dysfunction. Involvement of oxidative mtDNA damage in disorders characterized by chronic oxidative stress has been less thoroughly studied. Hypothesis: In the present study we tested the hypothesis that transgenic modulation of Ogg1, a DNA glycosylase mediating the first step in the base excision repair of oxidative mtDNA damage, coordinately regulates atherogenesis in mice fed a high fat diet. Methods: Wild type (WT) mice, Ogg1 knock-out (KO) mice and KO mice transgenically overexpressing mitochondria-targeted Ogg1 (KO-Tg) were fed pro-atherogenic Western type diet for 14 weeks and analyzed for mtDNA damage and signs of atherogenesis. Results: KO mice fed a high fat diet had increased oxidative mtDNA damage in cardiac tissue, whereas KO-Tg animals did not differ from WT mice (WT: 0.18 ± 0.04; KO: 0.35 ± 0.04; KO-Tg: 0.15 ± 0.01 lesions per 10 4 bp; n=3, P<0.05; quantitative Southern blot analysis). We did not observe significant atherosclerotic plaque formation in the aortic valve of animals from any group; however appearance of fatty streaks, indicative of early plaque development, was more evident in KO mice (WT: 179 ± 20; KO: 384 ± 59 pixels, n=4, P<0.05; immunohistochemistry for Fc receptor - general marker of inflammatory cells). This effect was completely blocked in KO-Tg mice. We found increased number of apoptotic cells in the aortic valve of KO, but not KO-Tg mice (WT: 2.00 ± 0.50; KO: 4.25 ± 0.48; KO-Tg: 2.14 ± 0.85 apoptotic cells, n=4, P<0.05; TUNEL assay). Conclusion: Our data demonstrate that Ogg1 deficiency in mice fed a high fat diet leads to increased oxidative mtDNA damage, appearance of fatty streaks and cell apoptosis. In contrast, enhancement of mtDNA repair with mitochondria-targeted Ogg1 reduces fatty streaks formation and apoptosis induced by a high fat diet. These results suggest mtDNA damage and repair could be important targets for atheroprotection.

RP105 deficiency attenuates early atherosclerosis via decreased monocyte influx in a CCR2 dependent manner

Objective: Toll like receptor 4 (TLR4) plays a key role in inflammation and previously it was established that TLR4 deficiency attenuates atherosclerosis. RadioProtective 105 (RP105) is a structural homolog of TLR4 and an important regulator of TLR4 signaling, suggesting that RP105 may also be an important effector in atherosclerosis. We thus aimed to determine the role of RP105 in atherosclerotic lesion development using RP105 deficient mice on an atherosclerotic background. Methods and results: Atherosclerosis was induced in Western-type diet fed low density lipoprotein receptor deficient (LDLr−/−) and LDLr/RP105 double knockout (LDLr−/−/RP105−/−) mice by means of perivascular carotid artery collar placement. Lesion size was significantly reduced by 58% in LDLr−/−/RP105−/− mice, and moreover, plaque macrophage content was markedly reduced by 40%. In a model of acute peritonitis, monocyte influx was almost 3-fold reduced in LDLr−/−/RP105−/− mice (P = 0.001), while neutrophil influx remained unaltered, suggestive of an altered migratory capacity of monocytes upon deletion of RP105. Interestingly, in vitro stimulation of monocytes with LPS induced a downregulation of CCR2, a chemokine receptor crucially involved in monocyte influx to atherosclerotic lesions, which was more pronounced in LDLr−/−/RP105−/− monocytes as compared to LDLr−/− monocytes. Conclusion: We here show that RP105 deficiency results in reduced early atherosclerotic plaque development with a marked decrease in lesional macrophage content, which may be due to disturbed migration of RP105 deficient monocytes resulting from CCR2 downregulation.

PKCε deficits in Alzheimer's disease brains and skin fibroblasts.

In Alzheimer's disease (AD) transgenic mice, activation of synaptogenic protein kinase C ε (PKCε) was found to prevent synaptotoxic amyloid-β (Aβ)-oligomer elevation, PKCε deficits, early synaptic loss, cognitive deficits, and amyloid plaque formation. In humans, to study the role of PKCε in the pathophysiology of AD and to evaluate its possible use as an early AD-biomarker, we examined PKCε and Aβ in the brains of autopsy-confirmed AD patients (n = 20) and age-matched controls (AC, n = 19), and in skin fibroblast samples from AD (n = 14), non-AD dementia patients (n = 14), and AC (n = 22). Intraneuronal Aβ levels were measured immunohistochemically (using an Aβ-specific antibody) in hippocampal pyramidal cells of human autopsy brains. PKCε was significantly lower in the hippocampus and temporal pole areas of AD brains, whereas Aβ levels were significantly higher. The ratio of PKCε to Aβ in individual CA1 pyramidal cells was markedly lower in the autopsy AD brains versus controls. PKCε was inversely correlated with Aβ levels in controls, whereas in AD patients, PKCε showed no significant correlation with Aβ. In autopsy brains, PKCε decreased as the Braak score increased. Skin fibroblast samples from AD patients also demonstrated a deficit in PKCε compared to controls and an AD-specific change in the Aβ-oligomer effects on PKCε. Together, these data demonstrate that the relationship between Aβ levels and PKCε is markedly altered in AD patients' brains and skin fibroblasts, reflecting a loss of protective effect of PKCε against toxic Aβ accumulation. These changes of PKCε levels in human skin fibroblasts may provide an accurate, non-invasive peripheral AD biomarker.

A numerical study of the effect of varied blood pressure on the stability of carotid atherosclerotic plaque.

BackgroundBlood pressure (BP) is associated with early atherosclerosis and plaque rupture because the BP variability can significantly affect the blood flow velocity and shear stress over the plaque. However, the mechanical response of BP variability to the plaque remains unclear. Therefore, we investigated the correlation between different maximum systolic blood pressure (SBP) and the stress distribution on plaque, as well as the stress over the plaque and blood velocity around the plaque using different BP variations, which are the BP variability in different phases during one cardiac cycle and beat-to-beat BP variability.MethodWe established a two-dimensional artery model with stenosis at the degree of 62.5%. Eight combinations of pulsatile pressure gradients between the inflow and outflow were implemented at the model. Three levels of fibrous cap thickness were taken into consideration to investigate the additional effect on the BP variability. Wall shear stress and stress/strain distribution over the plaque were derived as well as the oscillation shear index (OSI) to analyze the impact of the changing rate of BP.ResultThe stresses at diastole were 2.5% ± 1.8% lower than that at systole under the same pressure drop during one cycle. It was also found that elevated SBP might cause the immediate increment of stress in the present cycle (292% ± 72.3%), but slight reduction in the successive cycle (0.48% ± 0.4%).ConclusionThe stress/strain distribution over the plaque is sensitive to the BP variability during one cardiac cycle, and the beat-to-beat BP variability could cause considerable impact on the progression of atherosclerosis in long-term.

Leukocyte cathepsin C deficiency attenuates atherosclerotic lesion progression by selective tuning of innate and adaptive immune responses.

The protein degrading activity of cathepsin C (CatC), combined with its role in leukocyte granule activation, suggests a contribution of this cystein protease in atherosclerosis. However, no experimental data are available to validate this concept. CatC gene and protein expression were increased in ruptured versus advanced stable human carotid artery lesions. To assess causal involvement of CatC in plaque progression and stability, we generated LDLr(-/-)//CatC(-/-) chimeras by bone marrow transplantation. CatC(-/-) chimeras presented attenuated plaque burden in carotids, descending aorta, aortic arch and root, at both the early and advanced plaque stage. CatC was abundantly expressed by plaque macrophages and foam cells. CatC expression and activity were dramatically downregulated in plaques of CatC(-/-) chimeras, supporting a hematopoietic origin of plaque CatC. Our studies unveiled an unexpected feedback of CatC deficiency on macrophage activation programs and T helper cell differentiation in as much as that CatC expression was upregulated in M1 macrophages, whereas its deficiency led to combined M2 (in vitro) and Th2 polarization (in vivo). Our data implicate CatC has a role in the selective tuning of innate and adaptive immune responses, relevant to a chronic immune disease, such as atherosclerosis.

Current Animal Models of Alzheimer’s Disease: Challenges in Translational Research

GENERAL COMMENTARY article Front. Neurol., 29 September 2014Sec. Neuropharmacology https://doi.org/10.3389/fneur.2014.00182

Identified early stage mycosis fungoides from psoriasis and atopic dermatitis using non-invasive color contrast enhancement by LEDs lighting

Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma (CTCL) and may progress internally over time. MF is clinically categorized as poorly defined areas of erythema, flat patches, thin plaques, and tumors. The diagnosis of early stage of MF (patch and early plaque mycosis fungoides) has been a major diagnostic challenge in dermatology because of the lack of highly characteristic immunophenotypical markers and the heterogeneity of clinical presentations of MF. In this study, the spectrum of each picture element of the patient’s skin image was obtained by multi-spectral imaging technology (MSI). Spectra of normal or pathological skin were collected from 30 patients (10 early stage MF, 10 psoriasis vulgaris, and 10 atopic dermatitis). An algorithm combined with multi-spectral imaging and color reproduction technique is applied to find the best enhancement of the difference between normal and abnormal skin regions. Accordingly, an illuminant with specific intensity ratio of red, green, and blue LEDs is proposed, which has optimal color enhancement for MF detection. Compared with the fluorescent lighting commonly in the use now, the color difference between normal and inflamed skin can be improved from 11.8414 to 17.4002 with a 47 % increase, 8.7671 to 12.8544 with a 26.3 % increase, and 11.0735 to 17.2634 with a 34.3 % increase for MF, psoriasis, and atopic dermatitis patients, respectively, thus making medical diagnosis more efficient, so helping patients receive early treatment.

Relation of Obstructive Sleep Apnea to Coronary Artery Calcium in Non-Obese Versus Obese Men and Women Aged 45–75 Years

Sleep apnea and obesity are strongly associated, and both increase the risk for coronary artery disease. Several cross-sectional studies have reported discrepant results regarding the role obesity plays in the relation between sleep apnea and coronary artery calcium (CAC), a marker of subclinical coronary disease. The aim of the present study was to investigate the association between sleep apnea and the presence of CAC in a community cohort of middle-aged men and women without preexisting cardiovascular disease, stratified by body mass index (<30 vs ≥30 kg/m(2)). Participants underwent electron-beam computed tomography to measure CAC and underwent home sleep testing for sleep apnea. The presence of CAC was defined as an Agatston score >0. Sleep apnea was analyzed categorically using the apnea-hypopnea index. The sample was composed of primarily men (61%) and Caucasians (56%), with a mean age of 61 years. The prevalence of CAC was 76%. In participants with body mass indexes <30 kg/m(2) (n = 139), apnea-hypopnea index ≥15 (vs <5) was associated with 2.7-fold odds of having CAC, but the effect only approached significance. Conversely, in participants with body mass indexes ≥30 kg/m(2), sleep apnea was not independently associated with CAC. In conclusion, sleep apnea is independently associated with early atherosclerotic plaque burden in nonobese patients.

Perforin Expression in Plaque Psoriasis: An Immunohistochemical Study

ABSTRACTPsoriasis (PsO) is T-cell-mediated disease resulting from aberrant activation of both innate and adaptive immunity. Perforin is a multi-domain, pore-forming protein. It is located within the cytoplasm of CD 8 cytotoxic T cells (CTLs) and natural killer cells (NK). The aim of this study was to evaluate the immunohistochemical (IHC) expression of perforin in lesional and perilesional skin of chronic plaque psoriatic patient and correlate its expression with the standard clinico-pathological variables. This prospective case–control study was conducted on 50 PsO patients and 30 age- and gender-matched healthy subjects as a control group. There were high-significant differences between lesional and perilesional skin of plaque PsO patients as regards to IHC perforin status and localization (p < 0.001 for both). There was a high-significant difference between positive and negative perforin cases as regards to psoriasis area severity index (PASI) (p < 0.000). There were significant differences between mild and moderate-to-severe intensity of IHC perforin expression as regards to triggering factors and PASI (p = 0.02 and 0.03, respectively). Localization of IHC perforin positive lymphocytes in both epidermis and dermis was significantly associated with higher degree of acanthosis and higher degree of inflammatory infiltrates in comparison with positive cells located in dermis (p = 0.001 for both). Perforin might have a putative signaling in early and late plaque PsO. Plaque psoriatic patients with positive perforin expression could be a candidate for a future target therapy to stop the proposed scenario and achieve a therapeutic response.

Advancements toward a systems level understanding of the human oral microbiome.

Oral microbes represent one of the most well studied microbial communities owing to the fact that they are a fundamental part of human development influencing health and disease, an easily accessible human microbiome, a highly structured and remarkably resilient biofilm as well as a model of bacteria-bacteria and bacteria-host interactions. In the last 80 years since oral plaque was first characterized for its functionally stable physiological properties such as the highly repeatable rapid pH decrease upon carbohydrate addition and subsequent recovery phase, the fundamental approaches to study the oral microbiome have cycled back and forth between community level investigations and characterizing individual model isolates. Since that time, many individual species have been well characterized and the development of the early plaque community, which involves many cell–cell binding interactions, has been carefully described. With high throughput sequencing enabling the enormous diversity of the oral cavity to be realized, a number of new challenges to progress were revealed. The large number of uncultivated oral species, the high interpersonal variability of taxonomic carriage and the possibility of multiple pathways to dysbiosis pose as major hurdles to obtain a systems level understanding from the community to the gene level. It is now possible however to start connecting the insights gained from single species with community wide approaches. This review will discuss some of the recent insights into the oral microbiome at a fundamental level, existing knowledge gaps, as well as challenges that have surfaced and the approaches to address them.