Atherosclerotic Plaque Characteristics Research Articles

Associations between carotid atherosclerotic plaque characteristics determined by magnetic resonance imaging and improvement of cognition in patients undergoing carotid endarterectomy.

To determine the predictive value of carotid plaque characteristics for the improvement of cognition in patients with moderate-to-severe carotid stenosis after carotid endarterectomy (CEA), using vessel wall magnetic resonance imaging (MRI). This was a prospective cohort study. Patients with unilateral, moderate-to-severe carotid stenosis referred to the Peking University Third Hospital for CEA were prospectively recruited and underwent carotid vessel wall MRI within 1 week before CEA. We performed Montreal Cognitive Assessment (MoCA) within 1 week before and 3-4 days after CEA. The morphological and compositional characteristics of carotid plaques on MRI were evaluated. Improvement of cognition was defined as >10% increase of the total MoCA score after CEA compared with baseline. Carotid plaque characteristics were compared between patients with and without cognitive improvement. In total, 105 patients (91 males; mean age, 65.5±8.4 years) were included. The volume {48.0 [interquartile range (IQR), 21.0 to 91.6] vs. 16.3 (IQR, 8.1 to 53.1) mm3; P=0.005} and cumulative slice [4.0 (IQR, 3.0 to 7.0) vs. 3.0 (IQR, 2.0 to 5.0); P=0.019] of carotid calcification, and maximum percentage of calcification area [13.1% (IQR, 6.0% to 19.8%) vs. 6.2% (IQR, 3.7% to 10.8%); P=0.004] were significantly smaller in participants with cognitive improvement compared to those without. Univariate logistic regression analysis showed that volume [odds ratio (OR) =0.994; 95% confidence interval (CI): 0.989 to 1.000; P=0.043] and cumulative slice (OR =0.823; 95% CI: 0.698 to 0.970; P=0.020) of carotid calcification, and maximum percentage of calcification area (OR =0.949; 95% CI: 0.909 to 0.991; P=0.018) were significantly correlated with cognitive improvement. After adjusting for confounding factors, these associations remained statistically or marginally significant (volume: OR =0.994; 95% CI: 0.988 to 1.000; P=0.057; maximum percentage of calcification area: OR =0.937; 95% CI: 0.890 to 0.987; P=0.014; and cumulative slice: OR =0.791; 95% CI: 0.646 to 0.967; P=0.022). No significant associations were found between other plaque characteristics and cognitive improvement (all P>0.05). More than half of the participants with unilateral, moderate-to-severe carotid atherosclerotic stenosis had cognitive improvement. The size of calcification might be an effective indicator of cognitive improvement after CEA.

Influence of myocardial bridge on atherosclerotic plaque distribution and characteristics evaluated by near-infrared spectroscopy intravascular ultrasound

This study aims to clarify whether myocardial bridge (MB) could influence atherosclerotic plaque characteristics assessed using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) imaging. One hundred and sixteen patients who underwent percutaneous coronary intervention (PCI) using NIRS-IVUS imaging were included. MB was defined as an echo-lucent band surrounding left anterior descending artery (LAD). In MB patients, LAD was divided into three segments: proximal, MB, and distal segments. In non-MB patients, corresponding three segments were defined based on the average length of the above segments. Segmental maximum plaque burden and lipid content derived from NIRS-IVUS imaging in the section of maximum plaque burden were evaluated in each segment. Lipid content of atherosclerotic plaque was evaluated as lipid core burden index (LCBI) and maxLCBI4mm. LCBI is the fraction of pixels indicating lipid within a region multiplied by 1000, and the maximum LCBI in any 4-mm region was defined as maxLCBI4mm. MB was identified in 42 patients. MB was not associated with maximum plaque burden in proximal segment. LCBI and maxLCBI4mm were significantly lower in patients with MB than those without in proximal segment. Multivariable analysis demonstrated both MB and maximum plaque burden in proximal segment to be independent predictors of LCBI in proximal segment. Lipid content of atherosclerotic plaque assessed by NIRS-IVUS imaging was significantly smaller in patients with MB than those without. MB could be considered as a predictor of lipid content of atherosclerotic plaque when assessed by NIRS-IVUS imaging.

Myeloid LXR (Liver X Receptor) Deficiency Induces Inflammatory Gene Expression in Foamy Macrophages and Accelerates Atherosclerosis.

Cholesterol loaded macrophage foam cells are a prominent feature of atherosclerotic plaques. Single-cell RNA sequencing has identified foam cells as TREM2 (triggering receptor expressed on myeloid cells 2) positive populations with low expression of inflammatory genes, resembling the TREM2 positive microglia of neurodegenerative diseases. Cholesterol loading of macrophages in vitro results in activation of LXR (liver X receptor) transcription factors and suppression of inflammatory genes. To test the hypothesis that LXRs mediate anti-inflammatory effects in Trem2 expressing atherosclerotic plaque foam cells, we performed RNA profiling on plaque cells from hypercholesterolemic mice with myeloid LXR deficiency. Myeloid LXR deficiency led to a dramatic increase in atherosclerosis with increased monocyte entry, foam cell formation, and plaque inflammation. Bulk cell-RNA profiling of plaque myeloid cells showed prominent upregulation of inflammatory mediators including oxidative, chemokine, and chemotactic genes. Single-cell RNA sequencing revealed increased numbers of foamy TREM2-expressing macrophages; however, these cells had reduced expression of the Trem2 gene expression module, including phagocytic and cholesterol efflux genes, and had switched to a proinflammatory and proliferative phenotype. Expression of Trem2 was suppressed by inflammatory signals but not directly affected by LXR activation in bone marrow-derived macrophages. Our current studies reveal the key role of macrophage LXRs in promoting the Trem2 gene expression program and in suppressing inflammation in foam cells of atherosclerotic plaques.

Comparison of carotid atherosclerotic plaque characteristics between symptomatic patients with transient ischemic attack and stroke using high-resolution magnetic resonance imaging

BackgroundThis study aimed to compare the characteristics of carotid plaques between patients with transient ischemic attack (TIA) and ischemic stroke using magnetic resonance (MR) imaging.MethodsPatients with a recent ischemic stroke or TIA who exhibited atherosclerotic plaques of carotid arteries in the symptomatic sides determined by MR vessel wall imaging were recruited. The plaque morphology and compositions including intraplaque hemorrhage (IPH), lipid-rich necrotic-core (LRNC) and calcification were compared between TIA and stroke patients. Logistic regression was performed to relate the plaque characteristics to the types of ischemic events.ResultsA total of 270 patients with TIA or ischemic stroke were recruited. Stroke patients had a significantly higher prevalence of diabetes (42.2% vs. 28.2%, p = 0.021), greater mean wall area (35.1 ± 10.1 mm2 vs. 32.0 ± 7.7 mm2, p = 0.004), mean wall thickness (1.3 ± 0.2 mm vs. 1.2 ± 0.2 mm, p = 0.001), maximum normalized wall index (NWI)(63.9% ± 6.0% vs. 62.2% ± 5.9%, p = 0.023) and %volume of LRNC (9.7% ± 8.2% vs. 7.4% ± 7.9%, p = 0.025) in the carotid arteries compared to those with TIA. After adjustment for clinical factors, above characteristics of carotid arteries were significantly associated with the type of ischemic events. After further adjustment for maximum NWI, this association remained statistically significant (OR, 1.41; CI, 1.01–1.96; p = 0.041).ConclusionsIschemic stroke patients had larger plaque burden and greater proportion of LRNC in carotid plaques compared to those with TIA. This study suggests that ischemic stroke patients had more vulnerable plaques compared to those with TIA.

Predictive value of HDL function in patients with coronary artery disease: relationship with coronary plaque characteristics and clinical events

Background HDL is endowed with several metabolic, vascular, and immunoinflammatory protective functions. Among them, a key property is to promote reverse cholesterol transport from cells back to the liver. The aim of this study was to estimate the association of scavenger receptor class B type I (SR-BI)- and ATP binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux (the two major routes for cholesterol efflux to HDL) with the presence, extent, and severity of coronary artery disease (CAD), vascular wall remodelling processes, coronary plaque characteristics, and the incidence of myocardial infarction in the different subgroups of patients from the CAPIRE study. Methods Patients (n = 525) from the CAPIRE study were divided into two groups: low-risk factors (RF), with 0–1 RF (n = 263), and multiple-RF, with ≥2 RFs; within each group, subjects were classified as no-CAD or CAD based on the segment involvement score (SIS) evaluated by coronary computed tomography angiography (SIS = 0 and SIS > 5, respectively). SR-BI- and ABCA1-mediated cholesterol efflux were measured using the plasma of all patients. Results SR-BI-mediated cholesterol efflux was significantly reduced in patients with CAD in both the low-RF and multiple-RF groups, whereas ABCA1-mediated cholesterol efflux was similar among all groups. In CAD patients, multivariable analysis showed that SR-BI-mediated cholesterol efflux <25th percentile predicted cardiovascular outcome (odds ratio 4.1; 95% CI: 1.3–13.7; p = .019), whereas ABCA-1-mediated cholesterol efflux and HDL-C levels significantly did not. Despite this finding, reduced SR-BI-mediated cholesterol efflux was not associated with changes in high-risk plaque features or changes in the prevalence of elevated total, non-calcified, and low-attenuation plaque volume. Conclusion SR-BI-mediated cholesterol efflux capacity is lower in patients with diffuse coronary atherosclerosis. In addition, a lower SR-BI-mediated cholesterol efflux capacity is associated with the worst clinical outcomes in patients with CAD, independently of atherosclerotic plaque features. Key Messages Increased cholesterol efflux capacity, an estimate of HDL function, is associated with a reduced CVD risk, regardless of HDL-C levels. HDL-C levels are significantly lower in patients with CAD. Lower SR-BI-mediated cholesterol efflux capacity is observed in patients with diffuse coronary atherosclerosis and is associated with the worst clinical outcomes in patients with CAD, independently of atherosclerotic plaque features.

Significance of Insignificant Left Main Disease

Significance of Insignificant Left Main Disease

Correlation between characteristics of intracranial atherosclerotic plaques and ischemic stroke in high-resolution vascular wall MRI.

Intracranial atherosclerotic stenosis is a major cause of ischemic stroke, accounting for 30% of ischemic strokes in Asian populations. To investigate the relationship between the degree of arterial stenosis and enhancement grade of intracranial atherosclerotic disease (ICAD), the plaque characteristics in different remodeling patterns, and its potential impact. A total of 210 patients diagnosed with ICAD were enrolled in this retrospective study. Patients were divided into the middle cerebral artery (MCA) group (101 cases), posterior cerebral artery (PCA) group (14 cases), basilar artery (BA) group (71 cases), and intracranial segment of vertebral artery (VA) group (90 cases) according to the difference of diseased vessels. Data on presence or absence of ischemic infarction, intracranial vascular position of lesions, plaque characteristics, ICAD enhancement grade, remodeling index, and degree of arterial stenosis were collected for analysis. The incidence of ischemic infarction in enhancement grade 2 was significantly higher than that in enhancement grade 1 in MCA group (P = 0.019). Enhancement grade 2 of ICAD was an independent risk factor for the development of ischemic infarction (odds ratio = 4.60; 95% confidence interval: 1.91-11.03; P = 0.001). There was no significant statistical difference in infarct rate between different remodeling modalities (P>0.05). Enhancement grade of ICAD is significantly associated with the degree of stenosis and the occurrence of ischemic stroke, which varies in different intracranial vessels. The pattern of vascular remodeling varies among different intracranial vessels, and the pattern of vascular remodeling has a significant impact on plaque characteristics.

Analysis methods of coronary artery intravascular images: A review

Coronary artery disease is among one of the diseases human suffer most. Intravascular coronary arterial image analysis consists of denoising, segmentation, detection, and three-dimensional reconstruction, having a significant meaning for auxiliary diagnosis and treatment of coronary artery disease. Intravascular ultrasound (IVUS) and intravascular optical coherence tomography (IVOCT) are the two most commonly applied intravascular coronary arterial imaging techniques. Based on these fundamental imaging techniques, in recent years, many advanced technologies from traditional machine learning algorithms to deep learning methods were employed in the analysis of intravascular coronary arterial images and made huge progress in this field. In this survey, we reviewed more than one hundred papers published in top journals or conferences such as Neural Networks and MICCAI. These papers proposed approaches or schemes for the intravascular coronary arterial image analysis, including lumen border segmentation, atherosclerotic plaque characterization, media-adventitia segmentation, stent strut detection, and three-dimensional reconstruction. Our survey began with introducing coronary artery intravascular imaging techniques, essential neural networks, and deep learning and then presented an across-the-board review of methods, applications, and trends of intravascular image analysis. This survey is more comprehensive than other articles not only for its scope and reference number but also for discussing the future direction in this field. Compared to other review papers in this field, this article could assist beginners in constructing a basic knowledge frame of coronary artery intravascular image analysis methods and brought state-of-the-art progress in this field to fellow researchers. We hope this paper could benefit either the beginners for coronary arterial image analysis or experienced researchers.

Cylindrical Transducer Array for Intravascular Shear Wave Elasticity Imaging: Preliminary Development.

We present an intravascular ultrasound (IVUS) transducer array designed to enable shear wave elasticity imaging (SWEI) of arteries for the detection and characterization of atherosclerotic soft plaques. Using a custom dicing fixture, we have fabricated single-element and axially-segmented array transducer prototypes from 4.6-Fr to 7.6-Fr piezoceramic tubes, respectively. Focused excitation of the array prototype at 4 MHz yielded a focal gain of 5× in intensity, for an estimated 60 mW/cm2 [Formula: see text] and 1.6-MPa negative peak pressure at 4.5-mm range in water. The single-element transducer generated a peak radial displacement of [Formula: see text] in a uniform elasticity phantom, with axial shear waves detectable by an external linear array probe up to 5 mm away from the excitation plane. In a vessel phantom with a soft inclusion, the array prototype generated peak displacements of 2.2 and [Formula: see text] in the soft inclusion and vessel wall regions, respectively. A SWEI image of the vessel phantom was reconstructed, with measured shear wave speed (SWS) of 1.66 ± 0.91 m/s and 0.97 ± 0.59 m/s for the soft inclusion and vessel wall regions, respectively. The array prototype was also used to obtain a SWEI image of an ex vivo porcine artery, with a mean SWS of 3.97 ± 1.12 m/s. These results suggest that a cylindrical intravascular ultrasound (IVUS) transducer array could be made capable of SWEI for atherosclerotic plaque detection in coronary arteries.

Large Culprit Plaque and More Intracranial Plaques Are Associated with Recurrent Stroke: A Case-Control Study Using Vessel Wall Imaging.

Intracranial atherosclerotic plaque features are potential factors associated with recurrent stroke, but previous studies only focused on a single lesion, and few studies investigated them with perfusion impairment. This study aimed to investigate the association among whole-brain plaque features, perfusion deficit, and stroke recurrence. Patients with ischemic stroke due to intracranial atherosclerosis were retrospectively collected and categorized into first-time and recurrent-stroke groups. Patients underwent high-resolution vessel wall imaging and DSC-PWI. Intracranial plaque number, culprit plaque features (such as plaque volume/burden, degree of stenosis, enhancement ratio), and perfusion deficit variables were recorded. Logistic regression analyses were performed to determine the independent factors associated with recurrent stroke. One hundred seventy-five patients (mean age, 59 [SD, 12] years; 115 men) were included. Compared with the first-time stroke group (n = 100), the recurrent-stroke group (n = 75) had a larger culprit volume (P = .006) and showed more intracranial plaques (P < .001) and more enhanced plaques (P = .003). After we adjusted for other factors, culprit plaque volume (OR, 1.16 per 10-mm3 increase; 95% CI, 1.03-1.30; P = .015) and total plaque number (OR, 1.31; 95% CI, 1.13-1.52; P < .001) were independently associated with recurrent stroke. Combining these factors increased the area under the curve to 0.71. Large culprit plaque and more intracranial plaques were independently associated with recurrent stroke. Performing whole-brain vessel wall imaging may help identify patients with a higher risk of recurrent stroke.

Association of symptomatic atherosclerotic carotid arteries with plaque areas showing low densities on computed tomographic angiography

Intraplaque hemorrhage is a key feature of vulnerable carotid atherosclerotic plaque (CAP), associated with low densities (<25 Hounsfield units [HU]) on computed tomographic angiography (CTA). This study aimed to analyze CAP on routine CTA performed in patients with symptomatic and asymptomatic carotid stenosis undergoing carotid endarterectomy (CEA) by assessing HU of the CAP area showing the lowest density (CAPALD) using radiological tools available in daily clinical practice, and to compare CAPALD values between symptomatic and asymptomatic carotids. We retrospectively screened preoperative CTA scans of 206 consecutive adult patients undergoing CEA for symptomatic or asymptomatic stenosis. CAPALD values were compared between symptomatic and asymptomatic carotids. Asymptomatic carotids included arteries contralateral to the symptomatic CEA artery, and asymptomatic stenotic arteries undergoing CEA and their contralateral arteries. Carotids were excluded when there was <30% stenosis, or when CAP could not be identified or CAPALD could not be measured. In total, 95 symptomatic and 112 asymptomatic carotids (derived from 174 patients) were analyzed. In multivariate analysis, symptomatic arteries showed more severe stenosis (median 70% vs. 67%, p=0.0228) and lower CAPALD values (median 17 vs. 25 HU, p=0.049), whereas degree of stenosis and CAPALD values were not correlated (rho=-0.02, p=0.77). HU values of <25 were more frequent in symptomatic than asymptomatic carotids (68% vs. 47%, p=0.0022). On CTA, symptomatic carotids are associated with CAP areas with low densities. CTA analysis of CAP may be interesting to help identify vulnerable plaques at risk for future stroke, especially in patients lacking strict indications for CEA based on the current guidelines.

ZEB2 Shapes the Epigenetic Landscape of Atherosclerosis.

Smooth muscle cells (SMCs) transition into a number of different phenotypes during atherosclerosis, including those that resemble fibroblasts and chondrocytes, and make up the majority of cells in the atherosclerotic plaque. To better understand the epigenetic and transcriptional mechanisms that mediate these cell state changes, and how they relate to risk for coronary artery disease (CAD), we have investigated the causality and function of transcription factors at genome-wide associated loci. We used CRISPR-Cas 9 genome and epigenome editing to identify the causal gene and cells for a complex CAD genome-wide association study signal at 2q22.3. Single-cell epigenetic and transcriptomic profiling in murine models and human coronary artery smooth muscle cells were used to understand the cellular and molecular mechanism by which this CAD risk gene exerts its function. CRISPR-Cas 9 genome and epigenome editing showed that the complex CAD genetic signals within a genomic region at 2q22.3 lie within smooth muscle long-distance enhancers for ZEB2, a transcription factor extensively studied in the context of epithelial mesenchymal transition in development of cancer. Zeb2 regulates SMC phenotypic transition through chromatin remodeling that obviates accessibility and disrupts both Notch and transforming growth factor β signaling, thus altering the epigenetic trajectory of SMC transitions. SMC-specific loss of Zeb2 resulted in an inability of transitioning SMCs to turn off contractile programing and take on a fibroblast-like phenotype, but accelerated the formation of chondromyocytes, mirroring features of high-risk atherosclerotic plaques in human coronary arteries. These studies identify ZEB2 as a new CAD genome-wide association study gene that affects features of plaque vulnerability through direct effects on the epigenome, providing a new therapeutic approach to target vascular disease.

Pathophysiology and Role of Coronary CT Angiography in Stable Angina

관상동맥질환의 임상적인 개념은 지난 10년 동안 패러다임의 변화를 보여왔다. 관상동맥질환은 대부분 진행성 질환이며, 관상동맥질환 환자는 질병 진행의 어느 시점에서도 급성 관상동맥 증후군에 직면할 수 있다. 이러한 임상적 맥락에서 2019년 유럽심장학회 가이드라인에서는 조기 진단과 꾸준한 관리가 필요한 관상동맥질환의 임상적인 중요성을 반영하여 “만성 관상동맥증후군”이라는 용어의 사용을 발표하였다. 최근 관상동맥 전산화단층촬영 혈관조영술을 이용한 관상동맥질환의 평가는 많은 발전을 이루었고, 안정형 협심증 또는 만성 관상동맥증후군 환자에서 관상동맥 전산화단층촬영 혈관조영술의 임상적 유용성은 초기 무증상 관상동맥질환의 발견에서부터 죽상경화판의 특성 분석 및 관상동맥질환의 치료 전략 결정에 도움을 주는 역할까지 관상동맥질환의 다양한 단계에 걸쳐 입증되고 있다. 이 종설에서는 안정형 협심증 환자의 이해를 돕는 병태생리를 설명하고 이에 대한 관상동맥 전산화단층촬영의 임상적 적용과 역할에 대해 알아보고자 한다.

Morphologic Characterization of Atherosclerotic Plaque of Coronary Arteries Diseases by Multidetector Computed Tomography (MDCT)

A multidetector row computed tomography (MDCT) image is being considered as a possible alternative to current imaging methods for evaluating vessel anatomy and morphology of atherosclerotic plaques in a variety of arterial beds. It is possible to evaluate the entire arterial vasculature using MDCT. Furthermore, MDCT is capable of visualizing the vessel wall and of quantifying calcified and noncalcified plaques. In total, 72 patients (56.9% male and 43.1% female) with consecutive ages ranging fro

Macrophage-Specific IGF-1 Overexpression Reduces CXCL12 Chemokine Levels and Suppresses Atherosclerotic Burden in Apoe-Deficient Mice.

IGF-1 (insulin-like growth factor 1) exerts pleiotropic effects including promotion of cellular growth, differentiation, survival, and anabolism. We have shown that systemic IGF-1 administration reduced atherosclerosis in Apoe-/- (apolipoprotein E deficient) mice, and this effect was associated with a reduction in lesional macrophages and a decreased number of foam cells in the plaque. Almost all cell types secrete IGF-1, but the effect of macrophage-derived IGF-1 on the pathogenesis of atherosclerosis is poorly understood. We hypothesized that macrophage-derived IGF-1 will reduce atherosclerosis. Approach and Results: We created macrophage-specific IGF-1 overexpressing mice on an Apoe-/- background. Macrophage-specific IGF-1 overexpression reduced plaque macrophages, foam cells, and atherosclerotic burden and promoted features of stable atherosclerotic plaque. Macrophage-specific IGF1 mice had a reduction in monocyte infiltration into plaque, decreased expression of CXCL12 (CXC chemokine ligand 12), and upregulation of ABCA1 (ATP-binding cassette transporter 1), a cholesterol efflux regulator, in atherosclerotic plaque and in peritoneal macrophages. IGF-1 prevented oxidized lipid-induced CXCL12 upregulation and foam cell formation in cultured THP-1 macrophages and increased lipid efflux. We also found an increase in cholesterol efflux in macrophage-specific IGF1-derived peritoneal macrophages. Macrophage IGF-1 overexpression reduced atherosclerotic burden and increased features of plaque stability, likely via a reduction in CXCL12-mediated monocyte recruitment and an increase in ABCA1-dependent macrophage lipid efflux.

Characterization of atherosclerotic plaques in blood vessels with low oxygenated blood and blood pressure (Pulmonary trunk): role of growth differentiation factor-15 (GDF-15)

BackgroundGrowth differentiation factor (GDF)-15 is linked to inflammation, cancer, and atherosclerosis. GDF-15 is expressed in most tissues but is extremely induced under pathological conditions. Elevated serum levels are suggested as a risk factor and a marker for cardiovascular diseases. However, the cellular sources and the effects of GDF-15 on the cardiovascular system have not been completely elucidated including progression, and morphology of atherosclerotic plaques. Thus, this work aimed to characterize the influence of GDF-15 deficiency on the morphology of atherosclerotic plaques in blood vessels with low-oxygen blood and low blood pressure as the pulmonary trunk (PT), in hypercholesterolemic ApoE−/− mice.MethodsGDF-15−/− ApoE−/− mice were generated by crossbreeding of ApoE−/−- and GDF-15−/− mice. After feeding a cholesterol-enriched diet (CED) for 20 weeks, samples of the brachiocephalic trunk (BT) and PT were dissected and lumen stenosis (LS) was measured. Furthermore, changes in the cellularity of the PT, amounts of apoptosis-, autophagy-, inflammation- and proliferation-relevant proteins were immunohisto-morphometrically analyzed. Additionally, we examined an atherosclerotic plaque in a human post mortem sample of the pulmonary artery.ResultsAfter CED the body weight of GDF-15−/−ApoE−/− was 22.9% higher than ApoE−/−. Double knockout mice showed also an 35.3% increase of plasma triglyceride levels, whereas plasma cholesterol was similar in both genotypes. LS in the BT and PT of GDF-15−/−ApoE−/− mice was significantly reduced by 19.0% and by 6.7% compared to ApoE−/−. Comparing LS in PT and BT of the same genotype revealed a significant 38.8% (ApoE−/−) or 26.4% (GDF-15−/−ApoE−/−) lower LS in the PT. Immunohistomorphometry of atherosclerotic lesions in PT of GDF-15−/−ApoE−/− revealed significantly increased levels (39.8% and 7.3%) of CD68 + macrophages (MΦ) and α-actin + smooth muscle cells than in ApoE−/−. The density of TUNEL + , apoptotic cells was significantly (32.9%) higher in plaques of PT of GDF-15−/−ApoE−/− than in ApoE−/−. Analysis of atherosclerotic lesion of a human pulmonary artery showed sm-α-actin, CD68+, TUNEL+, Ki67+, and APG5L/ATG+ cells as observed in PT. COX-2+ and IL-6+ immunoreactivities were predominantly located in endothelial cells and subendothelial space. In BT and PT of GDF15−/−ApoE−/− mice the necrotic area was 10% and 6.5% lower than in ApoE−/−. In BT and PT of GDF15−/−ApoE−/− we found 40% and 57% less unstable plaques than ApoE−/− mice.ConclusionsAtherosclerotic lesions occur in both, BT and PT, however, the size is smaller in PT, possibly due to the effect of the low-oxygen blood and/or lower blood pressure. GDF-15 is involved in atherosclerotic processes in BT and PT, although different mechanisms (e.g. apoptosis) in these two vessels seem to exist.

Risk factors for carotid plaque progression after optimising the risk factor treatment: substudy results of the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the carotid Bifurcation Plaque Study (ANTIQUE)

Background and aimCarotid plaque progression contributes to increasing stroke risk. The study aims to identify factors influencing carotid plaque thickness progression after changing the preventive treatment to the ‘treating arteries...

Serum Biomarkers in Carotid Artery Disease.

Carotid artery disease is considered a major cause of strokes and there is a need for early disease detection and management. Although imaging techniques have been developed for the diagnosis of carotid artery disease and different imaging-based markers have been proposed for the characterization of atherosclerotic plaques, there is still need for a definition of high-risk plaques in asymptomatic patients who may benefit from surgical intervention. Measurement of circulating biomarkers is a promising method to assist in patient-specific disease management, but the lack of robust clinical evidence limits their use as a standard of care. The purpose of this review paper is to present circulating biomarkers related to carotid artery diagnosis and prognosis, which are mainly provided by statistical-based clinical studies. The result of our investigation showed that typical well-established inflammatory biomarkers and biomarkers related to patient lipid profiles are associated with carotid artery disease. In addition to this, more specialized types of biomarkers, such as endothelial and cell adhesion, matrix degrading, and metabolic biomarkers seem to be associated with different carotid artery disease outputs, assisting vascular specialists in selecting patients at high risk for stroke and in need of intervention.

Abstract 14060: Gender Difference in Atherosclerotic Plaque Characteristics and Vascular Morphology Features by Coronary CTA in Coronary Artery Disease With and Without Ischemia (CREDENCE Substudy)

Introduction: It is unknown whether gender differences exist in the atherosclerotic plaque characteristics (APCs) and vessel morphology of patients with and without ischemia. Hypothesis: There are no gender differences in the APCs or vessel morphology of patients with and without ischemia. Methods: The 303 patients in the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) trial were enrolled following referral for non-emergent invasive coronary angiography with 3-vessel FFR and subsequently underwent CCTA per study protocol. Ischemic vessels were defined by FFR &lt; 0.8 or vessel diameter stenosis &gt; 90% on invasive investigation. A blinded quantitative analysis using artificial intelligence software was used to quantify APCs visualized on CCTA throughout the coronary tree (Cleerly Labs, Cleerly Inc., New York). APCs and vessel morphology data were stratified by gender for further analysis. Results: Among the 303 patients in the study cohort, 162 (53.4%) patients (22.8% females) had ischemic vessels and 141 (46.6%) patients (36.2% females) had non-ischemic vessels. While men were more likely to use tobacco ( p &lt;0.0001), there were no other gender differences in the age or comorbidity profile of the cohort. On imaging, men had more total plaque (non-ischemic group only) ( p =0.018), low-density non-calcified plaque and non-calcified plaque (NCP) volume, as well as greater lesion length, and lumen volume than females. There were no gender differences in calcified plaque, remodeling, high risk plaques, stenosis diameter, or APCs normalized for vessel volume (PAV). Conclusion: In patients with and without ischemia, men have a higher prevalence of low-density NCP and total NCP volume, with no significant differences in remodeling or other atherosclerotic features. These composition plaque differences may be useful to determine gender-specific risks of coronary ischemia as compared to invasive FFR.

Abstract 10940: Leptin Treatment Protects the Endothelium from Inflammation, Increased Permeability and Endothelial-to-Mesenchymal Transition

Introduction: Patients with lipodystrophy (LD) are characterized by a loss of adipose tissue and are associated with a higher risk for cardiovascular diseases (CVD). As a consequence of adipose tissue reduction in LD patients, the systemic concentration of the adipokine leptin decreases, representing the pathological cause of this disease. Hypothesis: We hypothesized that the reduction of leptin may impair endothelial cells, leading to the development of CVD. Therefore, we analyzed the effects of leptin treatment on vascular inflammation, endothelial-to-mesenchymal transition (EndMT), endothelial permeability and atherosclerotic plaque characteristics. Methods &amp; Results: Treatment of endothelial cells with leptin (200 ng/ml, 6 h) potently reduced IL1β-induced inflammation, as measured by expression of ICAM1 (-25.1%) and E-Selectin (-22.7%), (both p&lt;0.05). Leptin further reduced the induction of EndMT, as determined by expression of calponin (-41.3%) and SM22 (-23.8%), (both p&lt;0.05), as well as the EndMT-induced endothelial permeability (-20.7%, p&lt;0.05). These data were confirmed in a combined lipodystrophic and atherosclerosis prone mouse model (LDLR -/- ;aP2-nSREBP). Treatment with leptin (3.0 mg/kg) for 8 w reduced the number of EndMT-positive endothelial cells (-69%, p&lt;0.05) as well as the total number of mesenchymal cells in the atherosclerotic lesions (-34.8%), (both p&lt;0.05). Further analysis of the atherosclerotic lesions revealed a reduction of atherosclerotic plaque protrusion into the vessel lumen (-31%) and reduced macrophage infiltration (-21.9%) (p&lt;0.05), which is a hallmark of instable atherosclerotic plaques that are prone to rupture, whereas the total plaque area was not affected. The expression of the leptin receptor (LepR) was reduced in endothelial cell inflammation, EndMT (-69%, p&lt;0.05) and in atherosclerotic lesions, suggesting reduced leptin effects under these conditions. Conclusions: Leptin treatment exerts beneficial effects protecting endothelial function and identity in lipodystrophy. Downregulation of the leptin receptor in diseased endothelial cells is likely to reduce the identified positive vascular effects of leptin signaling in lipodystrophy.