Types Of Atherosclerotic Plaques Research Articles

N-Terminal proteomic profiling reveals distinct fragmentation patterns of proteins in different types of human atherosclerotic plaques

N-Terminal proteomic profiling reveals distinct fragmentation patterns of proteins in different types of human atherosclerotic plaques

Drug-interacting gene expression levels differ between atherosclerotic plaque subtypes

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Dutch Heart foundation Recent transcriptomic-based clustering of human atherosclerotic plaques revealed that plaques have a diversity and complexity that cannot be accurately described by classical concepts. Previous plaque RNA sequencing that we performed in 654 lesions identified five major plaque types that reflect different mechanisms of progression of atherosclerotic disease. These include the following plaque subtypes: 0. Fibro-collagenous, 1. Intermediate, 2. Lipo-necrotic, 3. Fibro-inflammatory, and 4. Fibro-cellular. We hypothesize that these different plaque types may respond differentially upon drug treatment. Objective To assess differential expression levels of drug-responsive genes between the earlier described five plaque subtypes. For this in silico experiment, the differential expression of drug-responsive genes was examined after colchicine treatment in smooth muscle cells and endothelial cells. Methods To begin, a web-based search identified 46 published colchicine interacting genes. Then, colchicine was applied to cultured smooth muscle and endothelial cells to verify the publicly reported drug responsive genes. Next, we modelled the effect of colchicine on the five types of human atherosclerotic plaques for those genes that were considered drug responsive. This was achieved by projecting the in vitro derived expression changes onto the gene expression data from the carotid plaques of 654 patients who participated in the ATHERO-EXPRESS study. Besides colchicine, the same experimental approach was applied for atorvastatin and rofecoxib drug treatment. Finally, changes in drug responsive gene expression were validated with mice gene expression data. Results 34 out of the 46 publicly known colchicine interacting genes were differently expressed between plaque types (Figure 1). These genes included established determinants of cell motility and atherosclerosis development (SCD, ITGB1, Tubulins). Furthermore, in-silico colchicine treatment revealed colchicine's strong effect on the atherosclerotic plaques' transcriptome. We are currently assessing if these perturbations may lead to shifts in plaque subtypes and if these changes are reflected in mice transcriptomic data. Conclusion The pilot data demonstrated major differences in drug-interacting gene expression levels in advanced atherosclerotic lesions. Therefore, novel and standard drugs used to treat atherosclerosis may have varying effects depending on the atherosclerotic plaque subtype.

The role of ultrasound in the management of carotid artery disease after head and neck radiotherapy treatment

AbstractHead and neck cancers (HNC) are a significant cause of morbidity and mortality globally. Radiotherapy (RT) is used heavily in the treatment of HNCs and has undergone rapid development since the 1980s which has led to increased survival rates in this patient group. Carotid artery stenosis and an increased incidence of stroke and transient ischaemic attack (TIA) have all been repeatedly described as a side effect of head and neck RT with vascular fibrosis implicated in its pathogenesis. The appearance of RT induced carotid stenosis displays a different phenotype to typical atherosclerotic plaque which can be appreciated both in histology samples and on ultrasound imaging. Ultrasound may also have a role to play in screening HNC patients who undergo RT to identify those at risk of suffering cerebrovascular events.

Biomimicking Atherosclerotic Vessels: A Relevant and (Yet) Sub-Explored Topic.

Atherosclerosis represents the etiologic source of several cardiovascular events, including myocardial infarction, cerebrovascular accidents, and peripheral artery disease, which remain the leading cause of mortality in the world. Numerous strategies are being delineated to revert the non-optimal projections of the World Health Organization, by both designing new diagnostic and therapeutic approaches or improving the interventional procedures performed by physicians. Deeply understanding the pathological process of atherosclerosis is, therefore, mandatory to accomplish improved results in these trials. Due to their availability, reproducibility, low expensiveness, and rapid production, biomimicking physical models are preferred over animal experimentation because they can overcome some limitations, mainly related to replicability and ethical issues. Their capability to represent any atherosclerotic stage and/or plaque type makes them valuable tools to investigate hemodynamical, pharmacodynamical, and biomechanical behaviors, as well as to optimize imaging systems and, thus, obtain meaningful prospects to improve the efficacy and effectiveness of treatment on a patient-specific basis. However, the broadness of possible applications in which these biomodels can be used is associated with a wide range of tissue-mimicking materials that are selected depending on the final purpose of the model and, consequently, prioritizing some materials' properties over others. This review aims to summarize the progress in fabricating biomimicking atherosclerotic models, mainly focusing on using materials according to the intended application.

Association of ratios of monocyte/high-density lipoprotein cholesterol and neutrophil/high-density lipoprotein cholesterol with atherosclerotic plaque type on coronary computed tomography.

The monocyte/high-density lipoprotein cholesterol (HDL-C) ratio (MHR) and neutrophil/HDL-C ratio (NHR) are markers for inflammation and dyslipidaemia, which are important factors in atherosclerosis. Studies have linked MHR and NHR to the prediction, severity and prognosis of coronary artery disease. However, no study has explored their connection to plaque stability, specifically its calcific or soft/mixed content. Monocyte, neutrophil and HDL-C levels were examined in 99 patients who had coronary computed tomographic angiography (CTA) between January and August 2023. They were divided into three groups: a group of 42 healthy individuals (group 0) with no coronary artery plaque and an Agatson score of 0, an unstable plaque group (group 1) with 31 patients displaying mixed and/or soft plaque on CTA, and a stable plaque group (group 2) with 26 patients showing only calcific plaque. White blood cell (WBC), monocyte and neutrophil counts were significantly higher in group 1 patients compared to group 0 patients (group 0: WBC = 6.31 ± 0.97 × 103 cells/µl, monocytes = 0.40 ± 0.09 × 10³ cells/µl, neutrophils = 3.32 ± 0.81 × 10³ cells/µl; and group 1: WBC = 7.61 ± 1.95 × 10³ cells/µl, monocytes = 0.50 ± 0.11 × 10³ cells/µl, neutrophils = 4.19 ± 1.36 10³ cells/µl; p < 0.05). MHR and NHR were significantly higher in group 1 patients compared to group 0 patients (group 0: MHR = 0.0079 ± 0.0029, NHR = 0.063 ± 0.023 and group 1: MHR = 0.0102 ± 0.003, NHR = 0.085 ± 0.036, p < 0.05). The significant differences in MHR and NHR between the three groups were due to the differences between groups 0 and 1. MHR and NHR were significantly higher in group 1 patients, although there was no statistically significant difference between groups 1 and 2.

Cholesterol crystals induce mechanical trauma, inflammation, and neo-vascularization in solid cancers as in atherosclerosis

Background and aimsCancer and atherosclerosis share common risk factors and inflammatory pathways that promote their proliferation via vascular endothelial growth factor (VEGF). Because CCs cause mechanical injury and inflammation in atherosclerosis, we investigated their presence in solid cancers and their activation of IL-1β, VEGF, CD44, and Ubiquityl-Histone H2B (Ub-H2B), that promote cancer growth. MethodsTumor specimens from eleven different types of human cancers and atherosclerotic plaques were assessed for CCs, free cholesterol content and IL1-β by microscopy, immunohistochemistry, and biochemical analysis. Breast and colon cancer cell lines were cultured with and without CCs to select for expression of VEGF, CD44, and Ub-H2B. Western blot and immunofluorescence were performed on cells to assess the effect of CCs on signaling pathways. ResultsCancers displayed higher CC content (+2.29 ± 0.74 vs +1.46 ± 0.84, p < 0.0001), distribution (5.06 ± 3.13 vs 2.86 ± 2.18, p < 0.001) and free cholesterol (3.63 ± 4.02 vs 1.52 ± 0.56 μg/mg, p < 0.01) than cancer free marginal tissues and similarly for atherosclerotic plaques and margins (+2.31 ± 0.51 vs +1.44 ± 0.79, p < 0.02; 14.0 ± 5.74 vs 8.14 ± 5.52, p < 0.03; 0.19 ± 0.14 vs 0.09 ± 0.04 μg/mg, p < 0.02) respectively. Cancers displayed significantly increased expression of IL1-β compared to marginal tissues. CCs treated cancer cells had increased expression of VEGF, CD44, and Ub-H2B compared to control. By microscopy, CCs were found perforating cancer tumors similar to plaque rupture. ConclusionsThese findings suggest that CCs can induce trauma and activate cytokines that enhance cancer growth as in atherosclerosis.

The Effect of PCSK9 Inhibition on the Stabilization of Atherosclerotic Plaque Determined by Biochemical and Diagnostic Imaging Methods.

Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of atherosclerotic plaque instability (MRI). Cytokines such as osteopontin, osteoprotegerin, and metalloproteinase 9 could be used as the most recent markers to identify and track the efficacy of anti-atherosclerotic therapy. Patients with USG and MRI-verified unstable atherosclerotic plaque were included in the study. Biomarker concentrations were measured and compared before and after PCSK9 inhibitor therapy. Additionally, concentrations prior to treatment were correlated with MRI images of the carotid artery. After treatment with alirocumab, the concentrations of MMP-9 (p < 0.01) and OPN, OPG (p < 0.05) decreased significantly. Furthermore, the results of OPN, OPG, and MMP 9 varied significantly depending on the type of atherosclerotic plaque in the MRI assay. In stable atherosclerotic plaques, the concentrations of OPN and OPG were greater (p < 0.01), whereas the concentration of MMP9 correlated with the instability of the plaque (p < 0.05). We demonstrated, probably for the first time, that alirocumab therapy significantly decreased the serum concentration of atherosclerotic plaque markers. In addition, we demonstrated the relationship between the type of atherosclerotic plaque as determined by carotid MRI and the concentration of these markers.

Image and Laboratory Aspects of Carotid Atherosclerosis

Abstract Carotid atherosclerosis is a main risk factor for ischemic stroke. Plaque instability is determined by the morphological characteristics of the plaque and can be characterized by immunological biomarkers. The study aimed to examine the connection between serum levels of hs-CRP, fibrinogen, ICAM-1, VCAM-1 and carotid atherosclerosis and the different types of atherosclerotic plaques imaged by ultrasound and magnetic resonance. The study involved 120 patients with carotid atherosclerosis and 33 patients without carotid atherosclerosis. Blood samples were collected to analyze the serum level of hs-CRP, fibrinogen, ICAM-1 and VCAM-1. The ultrasound analysis included detection of atherosclerotic plaques in the internal carotid arteries, measurement of artery stenosis in percentage and determination of plaque types by the classification of Gray-Weales/Gerolacus. A small subset of 30 patients with carotid atherosclerosis performed 3T magnetic resonance imaging. Atherosclerotic plaques were classified into 8 types based on the modified MR classification of the American Heart Association. Significantly higher serum levels of hs-CRP (p &lt;0.001) and fibrinogen (p = 0.018) were observed in patients with carotid atherosclerosis compared to patients without atherosclerosis. Criterion values for hs-CRP &gt; 4.13mg/l and for fibrinogen &gt; 3.6 g/l were associated with the presence of carotid plaques with accuracy of 70%. No relation was observed between the investigated biomarkers, the artery stenosis and the types of atherosclerotic plaques determined by ultrasound and magnetic resonance diagnostic methods. Hs-CRP and fibrinogen are reliable serum markers whose increased serum concentrations are connected with the presence of carotid atherosclerosis.

Relationship of Atherosclerotic Plaque Structure with the History of COVID-19 in Patients Undergoing Coronary Computed Tomographic Angiography.

Although there is no sign of reinfection, individuals who have a history of coronavirus disease 2019 (COVID-19) may experience prolonged chest discomfort and shortness of breath on exertion. This study aimed to examine the relationship between atherosclerotic coronary plaque structure and COVID-19. This retrospective cohort comprised 1269 consecutive patients who had coronary computed tomographic angiography (CCTA) for suspected coronary artery disease (CAD) between July 2020 and April 2021. The type of atherosclerotic plaque was the primary outcome. Secondary outcomes included the severity of coronary stenosis as determined via the Coronary Artery Disease-Reporting and Data System (CAD-RADS) classification and the coronary artery calcium (CAC) score. To reveal the relationship between the history of COVID-19 and the extent and severity of CAD, propensity score analysis and further multivariate logistic regression analysis were performed. The median age of the study population was 52 years, with 53.5% being male. COVID-19 was present in 337 individuals. The median duration from COVID-19 diagnosis to CCTA extraction was 245 days. The presence of atherosclerotic soft plaque (OR: 2.05, 95% confidence interval [CI]: 1.32-3.11, P = 0.001), mixed plaque (OR: 2.48, 95% CI: 1.39-4.43, P = 0.001), and high-risk plaque (OR: 2.75, 95% CI: 1.98-3.84, P < 0.001) was shown to be linked with the history of COVID-19 on the conditional multivariate regression analysis of the propensity-matched population. However, no statistically significant association was found between the history of COVID-19 and the severity of coronary stenosis based on CAD-RADS and CAC score. We found that the history of COVID-19 might be associated with coronary atherosclerosis assessed via CCTA.

Relationship of cardiovascular risk factors, pericardial fat, and carotid thickness with coronary plaque type in patients with diabetes mellitus.

There is paucity of data on the potential predictors of coronary plaque types among patients with diabetes mellitus(DM). To assess the association of cardiovascular risk factors, pericardial fat volume (PFV) assessed by multi-detector CT(MDCT)angiography, and internal carotid intima media thickness with coronary atherosclerotic plaque types in patients with type 2 DM. Patients with suspected coronary artery disease who underwent 64-slice MDCT angiography were enrolled in this retrospective study. A total of 784 patients were enrolled in this study, 198 of whom had DM and 586 of whom did not. The prevalence of calcified and mixed plaques was significantly higher in the DM group than without DM group, while no significant difference was found in the distribution of non-calcified plaque between groups. There was significant association between smoking [OR(CI) = 4(2-10),P = 0.001] and increased age[OR(CI) = 1.1(1-1.3),P = 0.023] and calcified plaque presence. Regarding mixed and non-calcified plaque, increased PFV[OR(CI) = 1.1(1-1.3),P = 0.001] and positive family history[OR(CI) = 4(2-12),P = 0.049] showed a significant association with coronary mixed plaque presence while no significant association was observed between cardiovascular risk factors, PFV, and internal carotid intima media thickness and non-calcified plaque presence in patients with DM. Increased PFV showed significant and independent association with mixed coronary plaques development, which suggests that PFV may be used as an imaging marker for early detection of increased risk for future coronary events in patients with DM.

The Association of TWEAK with Coronary Artery Calcification in Patients with Chronic Kidney Disease.

ResumoFundamento O receptor fraco indutor de apoptose semelhante a fator de necrose tumoral solúvel (sTWEAK) é um membro da superfamília de TNF que tem um papel crítico na proliferação e inflamação na circulação arterial.Objetivos Este estudo prospectivo tem o objetivo de mostrar a relação entre os níveis de sTWEAK e calcificação da artéria coronária (CAC) em pacientes com doença renal crônica (DRC).Métodos Este estudo prospectivo incluiu 139 pacientes consecutivos que passaram por angiografia coronariana por tomografia computadorizada, por qualquer motivo, para síndromes coronarianas agudas, de agosto de 2020 a fevereiro de 2021. Um total de 12 pacientes foi excluído do estudo devido aos critérios de exclusão. Os pacientes foram divididos em dois grupos com base em terem um escore CAC menor que 400 (n=84) ou um escore de 400 ou mais (n=43). A significância foi presumida em p-valor bilateral <0,05.Resultados À medida que o escore CAC aumentou, os níveis de sTWEAK diminuíram de forma estatisticamente significativa e detectou-se uma relação forte entre níveis de sTWEAK e escore CAC (r: -0,779, p<0,001). A análise ROC revelou que o nível de corte ideal de sTWEAK para prever o escore CAC de 400 era 761 pg/mL com uma sensibilidade de 71% e especificidade de 73% (AUC: 0,78; IC 95%: 0,70-0,85; p <0,001).Conclusões Embora os estudos em larga escala tenham demonstrado uma correlação positiva entre os níveis de TFGe e sTWEAK, alguns estudos detectaram que o aumento nos níveis de sTWEAK estão associados a mortalidade e gravidade do sistema da artéria coronária em pacientes com DRC. Nossos resultados comprovam nossa hipótese de que os níveis de sTWEAK mostram calcificação coronária em vez de outros tipos de placas ateroscleróticas.

Atherosclerosis in Animals is a Separate Type of Atherosclerosis that has Nothing to do with the Two Types of Atherosclerosis in Humans

The article is presented in the form of a review and analysis of the literature, which additionally helps to reveal the mechanisms of the pathogenesis of the development of atherosclerosis in humans. A contemporary vision is refuted that animal models of atherosclerosis are completely similar to the two types of human atherosclerotic lesions. The use of incorrect information about the etiology and pathogenesis of atherosclerotic lesions in humans reduces and even completely interferes with the possibility to carry out effective treatment and prevention of cardiovascular diseases associated with atherosclerosis. The two types of human atherosclerotic plaques have very different characteristics compared to atherosclerotic plaques in animals. They have a completely different etiology, pathogenesis, have a completely different appearance and location relative to the artery wall, have a different structure of the fibrous cap, a different pathway of LDL and macrophages, a different location of lipid core, a different way and time of arterial occlusion, a different type of endothelial dysfunction, they interact in totally different way with the walls of the artery and still have many additional differences that make both human atherosclerotic lesions completely different from atherosclerotic lesion in animals. Types IV atherosclerotic lesions consist of one lipid core with molten extracellular lipid. Type V atherosclerotic lesions type is a long, concentric, soft, strong, elastic, yellow, uniform structure. Due to the large number of inconsistencies between atherosclerotic lesions in animals and the two types of atherosclerotic lesions in humans, it is neither possible nor reasonable to use animal models to study the development of atherosclerotic lesions in humans. The plaques appear in the lumen of the artery in just a few days, in places of a sharp narrowing of the artery caused by hyperstimulation of the nervous system. The plaques consist of LDL, which were glued together with fibrin filaments. It also doesn't allow to detect a very simple mechanism accountable for the pathological increase in LDL levels in people who do not have genetic abnormalities. This mechanism proposed by the author is described in the first article dedicated to the type V atherosclerotic lesions (“Cylindrical cholesterol plaque”).

Transcriptomic based clustering of advanced atherosclerotic plaques: Revisiting the lesion determinants that identify the vulnerable patient.

Background and Aims: The current definition of an advanced atherosclerotic plaque type is predominantly driven by pathology-based descriptions. Histo-pathological studies have been instrumental in revealing key processes leading to plaque thrombosis. However, the diversity of pathology-based lesion types demands the improvement of the discriminative value to identify the arterial segment at risk for a major thrombotic event. We hypothesized that transcriptomic analyses of plaques provide major added value to identify lesions at risk for a major thrombotic event and underlying pathogenetic mechanisms.

Study on the effect of antibiotics application in perioperative period on carotid artery and serum interleukin-6 in periodontitis rats with hyperlipidemia or diabetes

Objective: To investigate the effect of antibiotics application in perioperative period on carotid artery and serum interluekin-6 (IL-6) in chronic periodontitis (CP) rats with hyperlipidemia (HL) or diabetes mellitus (DM). Methods: The models of CP rats with HL or DM were established in different batches. The rats were divided into groups as follows: A and A' were normal control groups, n=7 in each group; B(HL) and B'(DM) were groups of HL and DM, n=7 in each; C(HL+CP) and C'(DM+CP) were groups of CP with HL and CP with DM, n=21 in each. After the establishment of the models, groups C and C' were divided into C1 and C1' non-intervention group, C2 and C2' simple tooth extraction group and C3 and C3' antibiotic-assisted tooth extraction, with 7 rats in each of the groups. Two time interventions were performed to extract experimental teeth (bilateral maxillary first and second molars) in groups C2, C2', C3 and C3'. Serum samples were collected at 5 time points before and after tooth extraction (T1: before the first tooth extraction; T2: one week after the first tooth extraction; T3, T4, T5: the first, third and fifth week after the second tooth extraction), respectively. The absolute content of IL-6 in serum was detected by enzyme-linked immunosorbent assay (ELISA). Ratio of the absolute content in the experimental groups and control groups were calculated as the relative content of IL-6. At the end of the experiments, all rats were euthanasia and the bifurcation vascular tissues of carotid artery were collected for the observation of the carotid artery pathology and plaque formation and the measurement of the thickness of carotid intimal-medial layer (IMT). Results: Carotid artery pathology observation showed the IMT in group C was significantly thickened and the group C2 was the most thickened one (compared with group A, P＜0.01). Elastic fibers in groups C1 and C2 were disordered or even broken and disappeared, presenting typical atherosclerotic plaques, which were diffuse calcium salt deposits in the intimal-medial layers and protrude into the lumen. Elastic fibers in group C3 were ranged in ordered relatively without obvious fracture and the number of plaques was significantly reduced. The vascular walls in rats of groups B' and C' were incomplete, the IMTs had no obvious changes, elastic fibers were ranged disorderly and broken and the smooth muscle cells had vacuolar changes. In group C2', the vascular wall was significantly thinned and calcified plaques appeared in the artery, which showed multiple calcification lesions penetrating through the intimal-medial layer or even the whole layer. The vascular wall of group C3' was integrity and the elastic fibers arranged relatively clutter-free, the number of plaques was reduced. Results of detections of IL-6 showed the relative contents of IL-6 in groups B, B', C1, and C1' increased with time. At T3 time point, the relative contents of IL-6 in groups C2 and C3 reached the peak, C2 was 10.4 times of group A and C3 was 9.5 times of group A, and then decreased to different low levels. At T5 point, comparisons of the relative contents of IL-6 showed C3 < C2 < C1 (3.2 times, 5.4 times, 9.6 times of group A, respectively). The relative contents of IL-6 in groups C2' and C3' reached the peak at T2 point (4.9 times and 4.5 times of group A, respectively), and then decline with time. At T5 point, comparisons of the relative contents of IL-6 showed C3'< C2'< C1' (1.2 times, 1.4 times and 3.1 times of group A, respectively). Conclusions: Blood vessels were observed more obvious thickened in the tooth extraction without antibiotic of HL+CP rats with calcifications increase. Blood vessels of DM+CP rats became thin and fragile and even the integrity was damaged. Perioperative use of antibiotics might reduce the carotid artery lesions and decrease serum levels of inflammatory cytokines.

Coronary Artery Bifurcation Angle Degree; Bifurcation Lesion Development and the Prognostic Impact

Abstract Background: Coronary artery bifurcation lesion is one of the challenges in coronary arteries revascularization. Hemo-dynamic factors, as bifurcation angle is widely recognized for its involvement in atherosclerotic plaque formation. Aim of Work: Our aim of this study was to detect the effect of coronary artery bifurcation angle degree on the development of bifurcation atherosclerosis using Computed Tomography Coronary Angiography [CTCA] and its prognos-tic impact. Patients and Methods: The study was included 221 patients having low and intermediate pretest probability for Coronary Artery Disease [CAD]. Coronary arteries were investigated with CTCA for detection of bifurcation lesions, assessment of bifurcation angle and bifurcation lesion type, then 1 year follow-up period for Acute Coronary Syndrome (ACS). Results: 138 patients were males (62%) and 83 were females (38%). The meanage group was 55.7±9.8 years old. Bifurcation lesions were higher at LAD-LCx (125 patients, 56.5%) than at LAD-major diagonal (104 patients, 47%), than at LCx-OM (56 patients, 25%) (p-value <0.0001). At LAD-LCx sites there were higher bifurcation angles in patients with atherosclerotic bifurcation lesions than patients without bifurcation lesions (77.32o±18.1o vs. 62.24o±18.2o, p-value 0.001), while there was no statistically significant difference as regard bifurcation angels at LAD-diagonal and LCx-OM bifurcation sites. There was no relation between bifurcation angle and type of atherosclerotic plaque at the three studied bifurcation sites. Patients with wider bifurcation angels regardless lesions severity or management protocol had higher rates of ACS. Conclusion: A strong relation between LM bifurcation angel and the development of atherosclerotic lesions was noted, where wider bifurcation angles are more prone for atherosclerotic lesions, and more prone to develop ACS.

Overlapping Genetic Background of Coronary Artery and Carotid/Femoral Atherosclerotic Calcification.

Background and objectives: Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary calcification (CAC) might incorporate genetic links between different arteries’ atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet. Materials and Methods: We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries. Results: CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S_hyper) were moderately heritable (0.67 [95% CI: 0.37–1] and 0.69 [95% CI: 0.38–1], respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 [95% CI: 0–0.76]). Age and sex-adjusted phenotypic correlation between CAC and 4segm_hyper was 0.48 [95% CI: 0.30–0.63] and the underlying genetic correlation was 0.86 [95% CI: 0.42–1]. Conclusions: Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization.

Spectral Differences Between Normal and Atherosclerotic Aorta

Ischemic heart disease associated with coronary artery atherosclerosis is a leading cause ofdeath in the world today. In addition to standard treatments such as balloon angioplasty, laser mediated angioplasty is being considered as a potential adjuvant or replacement. Nevertheless, experiments and clinical experience have demonstrated that laser angioplasty is associated with damage to normal vessel tissue, which can cause serious complications. To study the possibility of minimizing these effects by directing laser energy more specifically to atherosclerotic lesions, data concerning the spectral characteristics of normal and diseased artery are necessary. In the current study, the absorbance, reflection and fluorescence spectra of normal and atherosclerotic aortic wall tissue are defined, revealing that (i) spectral characteristics of atherosclerotic aorta wall samples are significantly differed from that of healthy vascular wall samples and (ii) based on a spectral analysis of vascular wall, it is possible to distinguish morphological types of atherosclerotic plaques (i.e., lipidic, calcified). The current study contributes to a more complete understanding of laser-tissue interactions that may, following more experimentation and technique development, result in an improvement of clinical laser angioplasty technique.

The accuracy and interobserver variability in the assessment of coronary atherosclerotic plaques by optical frequency domain imaging: involving five observers with different levels of coronary imaging

Abstract Background Whether optical frequency domain imaging (OFDI) images can realize pathological diagnosis of coronary atherosclerotic plaques, and whether its diagnostic accuracy of lesion types varies depending on the personal experience of the clinician caring for coronary intervention have not been elucidated. Purpose This study investigated the interobserver variability in characterizing atherosclerotic plaque types by OFDI for multiple OFDI observers with levels of different experience. Methods Three-hundred-thirty-three histological cross-sections from 21 autopsy hearts were co-registered with the corresponding OFDI images. Histological cross-sections were classified into the following 7 lesion types according to the modified AHA atherosclerosis classification by a single experienced pathologist blinded for OCT findings: adaptive intimal thickening (AIT), intimal xanthoma (IX), pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), calcified nodule (CN), and healed erosion/rupture (HER). The five OFDI observers, unaware of the histological diagnosis, provided a single diagnosis for each corresponding OFDI image. The OFDI observer 1 was an expert interventional cardiologist with sufficient experience in OFDI imaging, followed by the OFDI observer 2, 3, and 4 as middle career interventional cardiologists who had completed training ten, seven, and four years. The OFDI observer 5 was a young career interventional cardiologist. The diagnostic accuracy of lesion types for each OFDI observer was determined taking histology as a gold standard. Results On histological analysis, 13% of histological cross-sections were diagnosed as AIT, 5% as IX, 23% as PIT, 25% as FA, 27% as FC, 2% as CN, and 5% as HER. The overall agreement between OFDI diagnosis and histopathologic diagnosis for OFDI observer 1 to 5 was 77%, 62%, 61%, 56%, and 46% (k values of 0.71, 0.54, 0.54, 0.45, and 0.33), respectively. Although the performance for characterizing AIT and FC was excellent and comparable among all OFDI observers, the sensitivity and positive predictive value for characterizing IX, PIT and FA varied depending on the OFDI observers' years of experience (Table). The main causes of false-positive or -negative diagnosis of FA were IX and PIT for all OFDI observers. Conclusion The diagnostic accuracy of atherosclerotic tissue properties from OFDI images correlated with the observers' years of experience, subspecialty training in coronary imaging, which suggests that the interpretation of OFDI images requires expertise and can be challenging to a less experienced reader. Table 1 Funding Acknowledgement Type of funding source: None

Association of the Total White Blood Cell, Neutrophils, and Monocytes Count With the Presence, Severity, and Types of Carotid Atherosclerotic Plaque.

Background: Previous studies have indicated that white blood cells (WBCs) might contribute to the development of atherosclerosis. However, the associations of WBCs and WBC subgroups with carotid atherosclerotic plaque (CAP) have not been compared.Methods: A cross-sectional study including 3,569 healthy Chinese adults was conducted between January 2016 and December 2018 in Zhengzhou, China, to explore the associations of WBC and WBC subtypes with the presence, severity, and types of CAPs. Fasting peripheral venous blood was collected for measurement of the total WBC and WBC subtype counts. The size, composition, and types of CAPs in the common carotid artery, the internal carotid artery, and the external carotid artery were measured bilaterally using B-mode ultrasound.Results: The total WBC, neutrophil, and monocyte counts showed significant associations with the presence of CAPs in men, but not in women, with the adjusted odds ratios (95% CI) in the highest (compared to the lowest) quartile 1.99 (1.33–2.97), 1.65 (1.10–2.47), and 2.17 (1.41–3.18) (Ptrend = 0.004, Ptrend = 0.004, and Ptrend < 0.001), respectively. The three leukocyte counts were also significantly associated with the severity of CAPs, as judged by the count of CAPs, maximal internal carotid plaque thickness, and the plaque score (all P < 0.01, Ptrend < 0.05). Compared with individuals without CAPs, those with echolucent plaques had significantly increased total WBC and neutrophil counts, whereas those with polytype plaques had a significantly increased monocyte count.Conclusion: WBC, neutrophil, and monocyte counts were significantly associated with the presence, severity, and types of CAPs in a healthy Chinese population.

Effects of castration on atherosclerosis in Yucatan minipigs with genetic hypercholesterolemia.

Low plasma testosterone, either spontaneous or as a result of androgen deprivation therapy for prostate cancer, is associated with an increased risk of cardiovascular events. The underlying mechanism in humans is not understood. Experimental studies in mice have shown that castration facilitates atherogenesis and may increase signs of plaque vulnerability. Pigs used for translational atherosclerosis research have frequently been castrated for practical or commercial reasons, but the effect of castration on atherosclerosis has never been systematically evaluated in pigs. To study the effect of castration on atherosclerotic plaque burden and type in genetically modified minipigs with hypercholesterolemia. Newborn male Yucatan minipigs with transgenic overexpression of a human gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 were randomized to undergo orchiectomy (n = 8) or serve as controls (n = 6). Minipigs were started on high-fat diet at 3 months of age and the amount and composition of atherosclerotic lesions were analyzed at 12 months of age. Plasma lipid profiles and behavioral parameters were also assessed. Plasma lipids were slightly affected to a more atherogenic profile by orchiectomy, but atherosclerotic lesion size was unaltered in the LAD, thoracic aorta, abdominal aorta, and iliac arteries. The distribution of lesion types (xanthomas, pathological intimal thickening and fibroatheromas) were also not statistically different between groups in any of the examined vascular territories. The abdominal aorta developed the most advanced stages of disease with reproducible fibroatheroma formation, and here it was found that the area of necrotic core was significantly increased in orchiectomized pigs compared with controls. Orchiectomy also reduced aggressive behavior. Castration does not alter the burden of atherosclerosis in hypercholesterolemic Yucatan minipigs, but may increase necrotic core area in fibroatheromas.