Atherosclerotic Plaque Composition Research Articles

Cardiovascular Protective Properties of GLP-1 Receptor Agonists: More than Just Diabetic and Weight Loss Drugs.

Owing to their potent glucose-lowering efficacy and substantial weight loss effects, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now considered part of the frontline therapeutic options to treat both type 2 diabetes mellitus and nondiabetic overweight/obesity. Stemming from successful demonstration of their cardiometabolic modulation and reduction of major adverse cardiovascular events in clinical outcome trials, GLP-1 RAs have since been validated as agents with compelling cardiovascular protective properties. Studies spanning from the bench to preclinical and large-scale randomised controlled trials have consistently corroborated the cardiovascular benefits of this pharmacological class. Most notably, there is converging evidence that they exert favourable effects on atherosclerotic ischaemic endpoints, with preclinical data indicating that they may do so by directly modifying the burden and composition of atherosclerotic plaques. This narrative review examines the underlying pharmacology and clinical evidence behind the cardiovascular benefits of GLP-1 RAs, with particular focus on atherosclerotic cardiovascular disease. It also delves into the mechanisms that underpin their putative plaque-modifying actions, addresses existing knowledge gaps and therapeutic challenges and looks to future developments in the field, including the use of combination incretin agents for diabetes and weight loss management.

Cross-species single-cell RNA sequencing reveals divergent phenotypes and activation states of adaptive immunity in human carotid and experimental murine atherosclerosis.

The distinct functions of immune cells in atherosclerosis have been mostly defined by preclinical mouse studies. Contrastingly, the immune cell composition of human atherosclerotic plaques and their contribution to disease progression is only poorly understood. It remains uncertain whether genetic animal models allow for valuable translational approaches. Single cell RNA-sequencing (scRNA-seq) was performed to define the immune cell landscape in human carotid atherosclerotic plaques. The human immune cell repertoire demonstrated an unexpectedly high heterogeneity and was dominated by cells of the T-cell lineage, a finding confirmed by immunohistochemistry. Bioinformatical integration with 7 mouse scRNA-seq data sets from adventitial and atherosclerotic vascular tissue revealed a total of 51 identities of cell types and differentiation states, of which some were only poorly conserved between species and exclusively found in humans. Locations, frequencies, and transcriptional programs of immune cells in mouse models did not resemble the immune cell landscape in human carotid atherosclerosis. In contrast to standard mouse models of atherosclerosis, human plaque leukocytes were dominated by several T-cell phenotypes with transcriptional hallmarks of T-cell activation and memory formation, T-cell receptor-, and pro-inflammatory signaling. Only mice at the age of 22 months partially resembled the activated T-cell phenotype. In a validation cohort of 43 patients undergoing carotid endarterectomy, the abundance of activated immune cell subsets in the plaque defined by multi-color flow cytometry associated with the extend of clinical atherosclerosis. Integrative scRNA-seq reveals a substantial difference in the immune cell composition of murine and human carotid atherosclerosis - a finding that questions the translational value of standard mouse models for adaptive immune cell studies. Clinical associations suggest a specific role for T-cell driven (auto-) immunity in human plaque formation and -instability.

Amyloid beta is associated with carotid wall echolucency and atherosclerotic plaque composition

Circulating amyloid-beta 1–40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.

Development of a Neutron Activation Analysis Method for Studying the Elemental Composition of Atherosclerotic Plaques

Development of a Neutron Activation Analysis Method for Studying the Elemental Composition of Atherosclerotic Plaques

Deficiency of Abca1 and Abcg1 mediated cholesterol efflux pathways in smooth muscle cells enhances vasoconstriction but does not affect atherosclerosis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): VIDI grant from Netherlands Organization of Scientific Research (NWO). Rosalind Franklin Fellowship from the University Medical Center Groningen. Both to Marit Westerterp, PhD Smooth muscle cells (SMCs) regulate blood flow distribution and blood pressure via vasoconstriction mediated by α-adrenergic receptors (α-ARs). Plasma membrane cholesterol may affect α1-AR signaling, but consequences for SMC-mediated vasoconstriction are unclear. Cholesterol loading promotes SMC-to-macrophage transition in vitro, which may enhance atherosclerotic plaque vulnerability. The cholesterol transporters ATP Binding Cassette A1 and G1 (ABCA1/ABCG1) are highly expressed by SMCs and mediate cholesterol efflux to apolipoprotein A1 and high-density lipoprotein (HDL), respectively. The role of ABCA1/ABCG1-mediated cholesterol efflux pathways in SMC-mediated vasoconstriction and atherogenesis remains poorly understood. We generated mice with SMC-specific Abca1/Abcg1 deficiency on the low-density lipoprotein receptor deficient (Ldlr-/-) background by crossbreeding Abca1fl/flAbcg1fl/flLdlr-/- mice with Myh11-CreERT2 transgenic mice and feeding them tamoxifen-diet. To induce SMC cholesterol accumulation and atherogenesis, we fed Myh11-CreERT2Abca1fl/flAbcg1fl/flLdlr-/- and Myh11-CreERT2Ldlr-/- mice Western-type diet (WTD) for 16 weeks. Combined SMC-Abca1/Abcg1 deficiency increased vasoconstriction in aortic rings induced by the α1-AR agonist phenylephrine, with reversal by methyl-β-cyclodextrin, substantiating its cholesterol-dependency. Unexpectedly, SMC-Abca1/Abcg1 deficiency induced urinary bladder enlargement by &amp;gt;20-fold, resembling bladder outlet obstruction (BOO). This was reversed by the α1-AR antagonist tamsulosin, indicating its dependence on bladder neck SMC constriction. Moreover, SMC-Abca1/Abcg1 deficiency decreased SMC markers and increased macrophage- and fibroblast-markers in the bladder wall, enhancing collagen deposition, consistent with SMC transdifferentiation. However, after 16 weeks WTD, SMC-Abca1/Abcg1 deficiency did not affect atherosclerotic lesion size, fibrous cap thickness, necrotic core, collagen, or macrophage content, suggesting that SMCs in atherosclerotic plaques were not affected. This may be due to low Abca1/Abcg1 expression in intimal compared to medial SMCs. We uncover a new role of SMC cholesterol efflux pathways in suppressing α1-AR mediated vasoconstriction and bladder SMC transdifferentiation, decreasing BOO. Our data may provide a mechanistic link for the association between BOO and diabetes in humans, particularly because diabetes is associated with decreased cholesterol efflux. SMC-Abca1/Abcg1 deficiency did not affect atherosclerotic lesion size or plaque composition, presumably due to low Abca1/Abcg1 expression in intimal SMCs of atherosclerotic lesions, as shown in mice and humans.

Photon-Counting Computed Tomography in Atherosclerotic Plaque Characterization.

Atherosclerotic plaque buildup in the coronary and carotid arteries is pivotal in the onset of acute myocardial infarctions or cerebrovascular events, leading to heightened levels of illness and death. Atherosclerosis is a complex and multistep disease, beginning with the deposition of low-density lipoproteins in the arterial intima and culminating in plaque rupture. Modern technology favors non-invasive imaging techniques to assess atherosclerotic plaque and offer insights beyond mere artery stenosis. Among these, computed tomography stands out for its widespread clinical adoption and is prized for its speed and accessibility. Nonetheless, some limitations persist. The introduction of photon-counting computed tomography (PCCT), with its multi-energy capabilities, enhanced spatial resolution, and superior soft tissue contrast with minimal electronic noise, brings significant advantages to carotid and coronary artery imaging, enabling a more comprehensive examination of atherosclerotic plaque composition. This narrative review aims to provide a comprehensive overview of the main concepts related to PCCT. Additionally, we aim to explore the existing literature on the clinical application of PCCT in assessing atherosclerotic plaque. Finally, we will examine the advantages and limitations of this recently introduced technology.

Impact of endothelial shear stress on coronary atherosclerotic plaque progression and composition: A meta-analysis and systematic review

Background and aimsIntracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features. MethodsA systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis. ResultsThe meta-analysis encompassed 31′385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference −0.88, 95% CI −1.13 to −0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference −0.02, 95% CI −0.03 to −0.01) and fibrous plaque areas (mean difference −0.03, 95% CI −0.03 to −0.03). ConclusionThis meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making.

Characteristics of Atherosclerotic Plaques and Stroke Mechanism in Patients with Border-Zone Infarcts: A High-resolution Magnetic Resonance Imaging Study

BackgroundRelatively little is known about the plaque characteristics of border-zone infarcts and how they differ between cortical border-zone (CBZ) and internal border-zone (IBZ) infarcts. MethodsWe conducted a prospective observational cohort study of patients of intracranial atherosclerotic disease who underwent high-resolution magnetic resonance imaging (HR-MRI) examination. Individuals with border-zone infarcts in the middle cerebral artery (MCA) territory, detected by diffusion-weighted imaging, were enrolled. Plaque morphological and compositional parameters of both IBZ and CBZ groups were compared. Independent predictors were identified using a binary logistic regression model, and the sensitivity and specificity of the model were assessed using a receiver operating characteristic curve. Kaplan-Meier survival analysis further explored differences in stroke recurrence between BZ patients with mono or dual antiplatelet therapy. ResultsWe reviewed 101 symptomatic patients with border-zone infarcts (BZ) within the MCA territory in the study. Out of the patients meeting the imaging eligibility criteria, we detected 34 cases with isolated IBZ, 23 cases with isolated CBZ, and 6 cases with both IBZ and CBZ infarcts. Those with IBZ infarcts had a higher plaque burden than those without (p<0.001), and those with CBZ infarcts exhibited a complicated plaque less frequently than those without (37.9% vs 67.6%, p=0.018). In those with isolated IBZ or CBZ infarcts, plaque burden was independently associated with isolated IBZ infarcts (odd ratio=1.08; 95% CI, 1.02-1.15; p=0.023). During the median follow-up period of 37 (27, 50) months, 13.8% of patients receiving early dual antiplatelet treatment and 30.4% of those on single antiplatelet therapy experienced stroke recurrence (p=0.182). ConclusionsIntracranial atherosclerotic plaque morphology and composition differ between patients with IBZ and those with CBZ infarcts. Higher plaque burden is more associated with IBZ infarcts.

Predictors of coronary artery calcium burden in asymptomatic patients with newly diagnosed type 2 diabetes mellitus.

Long-standing diabetes mellitus is often associated with cardiovascular complications. We aimed to evaluate the presence, extent and composition of subclinical atherosclerotic plaques in coronary arteries by Computed Tomography in patients with newly diagnosed type 2 diabetes mellitus (NDT2DM), and to identify the predictors. In this study 101 consecutive patients with NDT2DM were included. Patients were categorized into five groups based on their Coronary Artery Calcium Score (CACS) ranging from 0, 0-10, 11-100, 101-400 to >400. All parameters were compared across these groups. The average patient age was 54.4 ± 11.6years and 48 (47.5%) were females. Eight (7.9%) patients had CACS 0, 6.9% CACS 1-10, 42.6% CACS 11-100, 22.8% CACS 101-400 and 19.8% had CACS >400. Multiple regression analysis for the general data identified weight (p = .04) and systolic blood pressure (p = .033) as independent predictors for CACS. Asymptomatic patients with NDT2DM in more than 90% of cases may present with calcified atherosclerotic plaques and this may be predicted by: patient weight and the level of systolic arterial pressure. Our study emphasizes the need for comprehensive care and early prevention of cardiovascular complications in individuals with NDT2DM.

Influence of intracoronary hemodynamic forces on atherosclerotic plaque phenotypes

Background and aimsCoronary hemodynamics impact coronary plaque progression and destabilization. The aim of the present study was to establish the association between focal vs. diffuse intracoronary pressure gradients and wall shear stress (WSS) patterns with atherosclerotic plaque composition. MethodsProspective, international, single-arm study of patients with chronic coronary syndromes and hemodynamic significant lesions (fractional flow reserve [FFR] ≤ 0.80). Motorized FFR pullback pressure gradient (PPG), optical coherence tomography (OCT), and time-average WSS (TAWSS) and topological shear variation index (TSVI) derived from three-dimensional angiography were obtained. ResultsOne hundred five vessels (median FFR 0.70 [Interquartile range (IQR) 0.56–0.77]) had combined PPG and WSS analyses. TSVI was correlated with PPG (r = 0.47, [95% Confidence Interval (95% CI) 0.30–0.65], p < 0.001). Vessels with a focal CAD (PPG above the median value of 0.67) had significantly higher TAWSS (14.8 [IQR 8.6–24.3] vs. 7.03 [4.8–11.7] Pa, p < 0.001) and TSVI (163.9 [117.6–249.2] vs. 76.8 [23.1–140.9] m−1, p < 0.001). In the 51 vessels with baseline OCT, TSVI was associated with plaque rupture (OR 1.01 [1.00–1.02], p = 0.024), PPG with the extension of lipids (OR 7.78 [6.19–9.77], p = 0.003), with the presence of thin-cap fibroatheroma (OR 2.85 [1.11–7.83], p = 0.024) and plaque rupture (OR 4.94 [1.82 to 13.47], p = 0.002). ConclusionsFocal and diffuse coronary artery disease, defined using coronary physiology, are associated with differential WSS profiles. Pullback pressure gradients and WSS profiles are associated with atherosclerotic plaque phenotypes. Focal disease (as identified by high PPG) and high TSVI are associated with high-risk plaque features. Clinical trial registrationhttps://clinicaltrials,gov/ct2/show/NCT03782688

Ezetimibe and atherosclerotic cardiovascular disease: a systematic review and meta-analysis

IntroductionIndividuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL-C-lowering effectiveness and the impact on coronary atherosclerotic plaque compositions of Ezetimibe has been lacking.MethodsWe conducted a systematic review by meticulously analyzing databases such as MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials that evaluated the efficacy of ezetimibe in lowering LDL-C levels and its influence on coronary atherosclerotic plaques among individuals with ACD. This review encompassed studies available until August 1, 2023. In our analysis, we employed the weighted mean difference (WMD) as the aggregated statistical measure, accompanied by the corresponding 95% confidence interval (CI).ResultsWe encompassed a total of 20 eligible studies. Our findings unveiled that the combined therapy involving ezetimibe alongside statins led to a more substantial absolute decrease in LDL-C in comparison to using statins alone. This difference in means amounted to (−14.06 mg/dl; 95% CI −18.0 to −10.0; p = 0.0001). Furthermore, upon conducting subgroup analyses, it became evident that the intervention strategies proved effective in diminishing the volume of dense calcification (DC) in contrast to the control group.ConclusionsOur study findings indicate that the inclusion of ezetimibe in conjunction with statin therapy leads to a modest yet meaningful additional reduction in LDL-C levels when compared to using statins in isolation. Importantly, the introduction of ezetimibe resulted in a significant decrease in the volume of DC. However, it is worth noting that further investigation is warranted to delve deeper into this phenomenon.

Smooth muscle-derived adventitial progenitor cells direct atherosclerotic plaque composition complexity in a Klf4-dependent manner.

We previously established that vascular smooth muscle-derived adventitial progenitor cells (AdvSca1-SM) preferentially differentiate into myofibroblasts and contribute to fibrosis in response to acute vascular injury. However, the role of these progenitor cells in chronic atherosclerosis has not been defined. Using an AdvSca1-SM cell lineage tracing model, scRNA-Seq, flow cytometry, and histological approaches, we confirmed that AdvSca1-SM-derived cells localized throughout the vessel wall and atherosclerotic plaques, where they primarily differentiated into fibroblasts, smooth muscle cells (SMC), or remained in a stem-like state. Krüppel-like factor 4 (Klf4) knockout specifically in AdvSca1-SM cells induced transition to a more collagen-enriched fibroblast phenotype compared with WT mice. Additionally, Klf4 deletion drastically modified the phenotypes of non-AdvSca1-SM-derived cells, resulting in more contractile SMC and atheroprotective macrophages. Functionally, overall plaque burden was not altered with Klf4 deletion, but multiple indices of plaque composition complexity, including necrotic core area, macrophage accumulation, and fibrous cap thickness, were reduced. Collectively, these data support that modulation of AdvSca1-SM cells through KLF4 depletion confers increased protection from the development of potentially unstable atherosclerotic plaques.

Association between high-intensity lipid-lowering therapy and atherosclerotic plaque content changes assed by iMAP-IVUS and near-infrared spectroscopy in patients with premature atherosclerosis

Abstract Background/Introduction The benefits of lipid-lowering drug treatment for the secondary prevention of coronary heart disease have been well-established by randomized, controlled trials. More evidence has now emerged to support the use of high-intensity low-density lipoprotein cholesterol (LDL-C) –lowering therapy including statine, ezetimibe, and PCSK9 inhibitors. Intravascular imaging, such as near-infrared spectroscopy (NIRS) can detect lipid-rich plaques. Virtual histology iMAP-Intravascular ultrasound (iMAP-IVUS) can classify tissue characteristics into 4 major components fibrotic, lipidic, necrotic, and calcified. Purpose Our study aimed to evaluate atherosclerotic plaque composition in very high cardiovascular-risk patients, who received high-intensity lipid-lowering therapy for 15 months. Methods Our study included stable coronary artery disease patients receiving statin and/or ezetimibe in maximum tolerated dose for at least one month, who were scheduled for PCI. In case LDL-C was &amp;gt;1.8 mmol/l, inclisiran was added to the therapy at the time of inclusion and continued for 15 months. The region of interest was a proximal or middle segment with angiographic evidence of nonobstructive de novo atherosclerosis &amp;gt;20% and &amp;lt;50%, evaluated by NIRS and iMAP-IVUS at baseline and 15 months later. After 15 months patients were classified into two groups – those who reached the European Society of Cardiology LDL-C target &amp;lt;1.8 mmol/L and those who did not. Statistical analysis was carried out with SPSS Statistics software, defining a significance level of 0.05. Results 37 eligible patients had undergone IVUS/NIRS investigation. The mean patient age was 53 years. After 15 months the mean LDL-C level decreased from 2.70 mmol/L to 1.79 mmol/l and 25 patients reached a target of &amp;lt;1.8 mmol/L. In the patient group that reached target - 4mm plaque lipid core burden index (LCBImax4mm) decreased from 184.00 (±160.07) to 62.72 (±142.19) with p=0.001 and total LCBI changed from 37.04 (± 40.80) to 15.60 (± 27.87) with p = 0.007. In patients with LDL-C &amp;gt;1.8 mmol/L, LCBImax4mm changed from 211.16 (±167.76) to 125.04 (±152.21) with no statistically significant difference p = 0.074. Similarly, the total LCBI was from 40.33 (± 43.38) to 22.41 (± 24.97) with p = 0.086. In iMAP-IVUS results necro-lipidic core in the &amp;lt;1.8 mmol/L group changed from 78.50 mm3 (±42.77) to 84.77 mm3 (±46.03) p = 0.422. Yet, second group's necro-lipidic core changed from 97.43 mm3 (±58.04) to 89.40 mm3 (±49.03), with no statistically significant difference p = 0.066. Additionally in both groups were significant changes in fibrotic tissues, for the target group from 139.50 mm3 (±69.86) to 147.32 mm3 (±73.56) p = 0.002 and from 149.71 mm3 (±82.79) to 160.09 mm3 (±89.01) p = 0.008 in second group. Conclusion Our study showed that after 15 months of high-intensity lipid-lowering therapy, patients that reached LDL-C levels &amp;lt;1.8 mmol/L, showed lower LCBImax4mm and total LCBI.

Comparison of Atherosclerotic Plaque Compositions in Diabetic and Non-diabetic Patients.

Diabetes mellitus is one of the major risk factors for coronary artery disease. Intravascular ultrasound(IVUS)imaging has an important role in the evaluation of atherosclerotic coronary artery disease. The aim of the study was to investigate the potential link between diabetes mellitus and plaque vulnerability in patients with coronary artery disease. In total, 26 patients with acute coronary syndrome (eight with diabetes mellitus) and 34 with stable angina pectoris (16 with diabetes mellitus) constituted the study population. Patients underwent IVUS ultrasound and virtual histology (VH)-IVUS imaging during routine diagnostic catheterization procedures. A total of 70 plaques in 60 patients were examined. Patients with diabetes mellitus had a significantly greater percentage of fibrofatty components in the minimal lumen area (MLA) (17± 12 in diabetics; 12± 6 in non-diabetics; p=0.06). Thin-cap fibroatheromaswere more frequent in patients with diabetes mellitus (72% versus 45%; p=0.012). There was a positive correlation between the presence of attenuated plaque and hemoglobin A1C (HbA1c) levels as well (7.09 ± 1.66 versus 6.02 ± 1.00; p=0.011). Patients with HbA1C ≥7.5% also had the highest prevalence of attenuated plaque. As shown by VH-IVUS, the prevalence of vulnerable plaques in patients with diabetes mellitus was much higher than that in non-diabetic patients. The presence of attenuated plaque detected in grayscale intravascular ultrasonography was associated with high HbA1C levels in diabetic patients. Diabetes mellitus may cause cardiovascular vulnerability by changing the plaque morphology.

Quantification of carotid plaque composition with a multi-contrast atherosclerosis characterization (MATCH) MRI sequence.

Carotid atherosclerotic plaques with a large lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and a thin or ruptured fibrous cap are associated with increased stroke risk. Multi-sequence MRI can be used to quantify carotid atherosclerotic plaque composition. Yet, its clinical implementation is hampered by long scan times and image misregistration. Multi-contrast atherosclerosis characterization (MATCH) overcomes these limitations. This study aims to compare the quantification of plaque composition with MATCH and multi-sequence MRI. MATCH and multi-sequence MRI were used to image 54 carotid arteries of 27 symptomatic patients with ≥2 mm carotid plaque on a 3.0 T MRI scanner. The following sequence parameters for MATCH were used: repetition time/echo time (TR/TE), 10.1/4.35 ms; field of view, 160 mm × 160 mm × 2 mm; matrix size, 256 × 256; acquired in-plane resolution, 0.63 mm2× 0.63 mm2; number of slices, 18; and flip angles, 8°, 5°, and 10°. Multi-sequence MRI (black-blood pre- and post-contrast T1-weighted, time of flight, and magnetization prepared rapid acquisition gradient echo; acquired in-plane resolution: 0.63 mm2 × 0.63 mm2) was acquired according to consensus recommendations, and image quality was scored (5-point scale). The interobserver agreement in plaque composition quantification was assessed by the intraclass correlation coefficient (ICC). The sensitivity and specificity of MATCH in identifying plaque composition were calculated using multi-sequence MRI as a reference standard. A significantly lower image quality of MATCH compared to that of multi-sequence MRI was observed (p < 0.05). The scan time for MATCH was shorter (7 vs. 40 min). Interobserver agreement in quantifying plaque composition on MATCH images was good to excellent (ICC ≥ 0.77) except for the total volume of calcifications and fibrous tissue that showed moderate agreement (ICC ≥ 0.61). The sensitivity and specificity of detecting plaque components on MATCH were ≥89% and ≥91% for IPH, ≥81% and 85% for LRNC, and ≥71% and ≥32% for calcifications, respectively. Overall, good-to-excellent agreement (ICC ≥ 0.76) of quantifying plaque components on MATCH with multi-sequence MRI as the reference standard was observed except for calcifications (ICC = 0.37-0.38) and fibrous tissue (ICC = 0.59-0.70). MATCH images can be used to quantify plaque components such as LRNC and IPH but not for calcifications. Although MATCH images showed a lower mean image quality score, short scan time and inherent co-registration are significant advantages.

The Contribution of Vascular Proteoglycans to Atherothrombosis: Clinical Implications.

The vascular extracellular matrix (ECM) produced by endothelial and smooth muscle cells is composed of collagens and glycoproteins and plays an integral role in regulating the structure and function of the vascular wall. Alteration in the expression of these proteins is associated with endothelial dysfunction and has been implicated in the development and progression of atherosclerosis. The ECM composition of atherosclerotic plaques varies depending on plaque phenotype and vulnerability, with distinct differences observed between ruptured and erodes plaques. Moreover, the thrombi on the exposed ECM are diverse in structure and composition, suggesting that the best antithrombotic approach may differ depending on plaque phenotype. This review provides a comprehensive overview of the role of proteoglycans in atherogenesis and thrombosis. It discusses the differential expression of the proteoglycans in different plaque phenotypes and the potential impact on platelet function and thrombosis. Finally, the review highlights the importance of this concept in developing a targeted approach to antithrombotic treatments to improve clinical outcomes in cardiovascular disease.

Shear stress and plaque microenvironment induce heterogeneity: A multiscale microenvironment evolution model

BackgroundBoth clinical images and in vivo observations have demonstrated the heterogeneity in atherosclerotic plaque composition. However, the quantitative mechanisms that contribute to the heterogeneity, such as the wall shear stress (WSS) and the interplays among microenvironmental factors are still unclear. MethodsWe develop a multiscale model coupling computational fluid dynamics, interactions of microenvironmental factors and evolutions of cellular behaviors to investigate the formation of plaque heterogeneity in a three-dimensional vessel segment. The model involves WSS, lipid deposition and inflammatory response to reveal the dynamic balance existed between the lipid metabolism and the phagocytosis of macrophages. ResultsThe dynamic balance in microenvironment is influenced by both the WSS and the interactions with microenvironmental factors, and consequently results in the longitudinal heterogeneity observed in plaque pathology. In addition, plaque heterogeneity can be reduced by decreasing low WSS area at downstream, as well as by altering the phagocytic abilities of macrophage on lipoproteins, which may be used to develop future plaque regression strategies. ConclusionsThis multiscale modeling provides a framework to understand the mechanisms in dynamics of plaque composition and also provides quantitative information to better risk stratification of plaque vulnerability in future clinical practice.

Meta-analysis and trial sequential analysis of ezetimibe for coronary atherosclerotic plaque compositions.

Background: Lipid aggregation, inflammatory cell infiltration, fibrous cap formation, and disruption are the major causes of atherosclerotic cardiovascular disease (ASCVD) and the pathologic features of atherosclerotic plaques. Although ezetimibe's role in decreasing blood lipids is widely known, there are insufficient data to determine which part of the drug has an effect on atherosclerotic plaque compositions. Objective: The study aimed to systematically evaluate the efficacy of ezetimibe for coronary atherosclerotic plaque compositions. Methods: Two researchers independently searched the PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) on the efficacy of ezetimibe for coronary atherosclerotic plaques from inception until 22 January 2023. The meta-analysis and trial sequential analysis (TSA) were performed using Stata 14.0 and TSA 0.9.5.10 Beta software, respectively. Results: Four RCTs were finally included this study, which comprised 349 coronary artery disease patients. Meta-analysis findings showed that, compared with the control group, intervention measures could effectively reduce the fibro-fatty plaque (FFP) volume [WMD = -2.90, 95% CI (-4.79 and -1.00), and p = 0.003 < 0.05]; there were no significant difference in the reduction of fibrous plaque (FP) volume [WMD = -4.92, 95% CI (-11.57 and 1.74), and p = 0.15 > 0.05], necrotic core (NC) volume [WMD = -2.26, 95% CI (-6.99 and 2.46), and p = 0.35 > 0.05], and change dense calcification (change DC) volume [WMD = -0.07, 95% CI (-0.34 and 0.20), and p = 0.62 > 0.05] between the treatment group and the control group. TSA findings showed more studies are still required to confirm the efficacy of ezetimibe for FP and NC in the future. Conclusion: Compared to the control group, ezetimibe significantly decreased FFP, but it had no statistically significant difference on FP, NC, or change DC. According to TSA, further research will be required to confirm the efficacy of ezetimibe for FP and NC in the future.

Atherosclerotic plaque composition and specific endovascular considerations in the end stage renal disease patients: a narrative review.

Vascular calcification (VC) and resulting vascular disease is one of the major causes of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). CKD itself is increasingly recognized as a risk factor for cardiac and peripheral arterial disease (PAD). This paper examines the atherosclerotic plaque composition and specific endovascular considerations in the end stage renal disease (ESRD) patients. The literature was reviewed regarding the current status of medical and interventional management arteriosclerotic disease in patients with CKD. Lastly, three representative cases displaying typical endovascular treatment options are provided. A literature search was performed in PubMed covering publications up to September 2021 as well as discussion with experts in the field. The high prevalence of atherosclerotic lesions in patients with chronic renal failure and high (re-)stenosis cause problems in the medium and long term as vascular calcium load represents one of the most widely encountered predictors of failure of endovascular treatment of PAD and future cardiovascular events (e.g., coronary calcium score). Patients with CKD also suffer from a greater risk for major vascular adverse events in general and worse revascularization outcomes following peripheral vascular intervention. A correlation between calcium burden and drug-coated balloon (DCB) performance has been established for PAD necessitating the need for different tools to cope with vascular calcium such as endoprosthesis or braided stents. Patients with CKD are at a higher risk of developing contrast-induced nephropathy (CIN). In addition to recommendations such as the administration of intravenous fluids, carbon dioxide (CO2) angiography is one option to potentially provide an effective and safe alternative both to iodine-based contrast media allergy and to the use of iodine-based contrast media in patients with CKD. Management and endovascular procedures of patients with ESRD are complex. In the course of time, new endovascular therapy methods have been developed such as directional atherectomy (DA) and the so-called "pave-and-crack" technique to deal with high vascular calcium burden. Besides interventional therapy, vascular patients with CKD benefit from aggressive medical management.

Evaluation of Cholesterol Thickness of Blood Vessels Using Photoacoustic Technology.

One of the primary indicators of plaque vulnerability is the lipid composition of atherosclerotic plaques. Therefore, the medical industry requires a method to evaluate necrotic nuclei in atherosclerosis imaging with sensitivity. In this regard, photoacoustic imaging is a plaque detection method that provides chemical information on lipids and cholesterol thickness in the arterial walls of the patient. This aspect aims to increase the low-frequency axial resolution by developing a new photoacoustic-based system. A photoacoustic system has been developed to detect the cholesterol thickness of the blood vessels to observe the progression of plaque in the heart's blood vessels. The application of the coherent photoacoustic discontinuous correlation tomography technique, which is based on a novel signal processing, significantly increased the cholesterol oleate's sensitivity to plaque necrosis. By enhancing the quality of thickness detection, the system for measuring the thickness of cholesterol in blood vessels has been reduced to approximately 23 microns. The results show that the phase spectrum peaked at 100 Hz at 58.66 degrees, and at 400 Hz, the phase spectrum was 46.37 degrees. The minimum amplitude is 1.95 at 100 Hz and 17.67 at 400 Hz. In conclusion, it can be stated that photoacoustic imaging as a method based on new technologies is of great importance in medical research, which is based on the use of nonionizing radiation to perform diagnostic processes and measure different types of body tissues.