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Atherosclerosis Jun 2024Cardiovascular diseases (CVD), including coronary heart disease and stroke, comprise the number one cause of mortality worldwide. A major contributor to CVD is... (Review)
Review
Cardiovascular diseases (CVD), including coronary heart disease and stroke, comprise the number one cause of mortality worldwide. A major contributor to CVD is atherosclerosis, which is a low-grade inflammatory disease of vasculature that involves a pathological build-up of plaque within the arterial walls. Studies have shown that regulation of gene expression via transcription factors and epigenetic mechanisms play a fundamental role in transcriptomic changes linked to the development of atherosclerosis. Chromatin remodeling is a reversible phenomenon and studies have supported the clinical application of chromatin-modifying agents for the prevention and treatment of CVD. In addition, pre-clinical studies have identified multiple transcription factors as potential therapeutic targets in combating atherosclerotic CVD. Although interaction between transcription factors and epigenetic mechanisms facilitate gene regulation, a limited number of studies appreciate this crosstalk in the context of CVD. Here, we reviewed this gene regulatory mechanism underappreciated in atherosclerosis, which will highlight the mechanisms underlying novel therapeutics targeting epigenetic modifiers and transcription factors in atherosclerosis.
PubMed: 38917706
DOI: 10.1016/j.atherosclerosis.2024.117615 -
Giornale Italiano Di Cardiologia (2006) Jul 2024
Topics: Humans; Plaque, Atherosclerotic; Coronary Artery Disease
PubMed: 38916470
DOI: 10.1714/4282.42642 -
Giornale Italiano Di Cardiologia (2006) Jul 2024
Topics: Humans; Plaque, Atherosclerotic; Randomized Controlled Trials as Topic; Coronary Artery Disease; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38916459
DOI: 10.1714/4282.42631 -
The Egyptian Heart Journal : (EHJ) :... Jun 2024This comprehensive review explores the multifaceted role of sortilin, a key receptor in lipid metabolism, within the context of cardiovascular diseases (CVDs), the... (Review)
Review
BACKGROUND
This comprehensive review explores the multifaceted role of sortilin, a key receptor in lipid metabolism, within the context of cardiovascular diseases (CVDs), the leading cause of global mortality.
MAIN BODY
Sortilin, encoded by the SORT1 gene, is implicated in the pathogenesis of atherosclerosis, primarily through its regulation of low-density lipoprotein cholesterol (LDL-C) and very low-density lipoproteins (VLDL). The review delves into the biological functions of sortilin, emphasizing its critical role in lipid and cholesterol homeostasis and its influence on hepatic secretion of lipoproteins and atherogenesis. We highlight sortilin's pathophysiological significance in atherosclerosis, underscoring its involvement in lipid metabolism pathways and vascular inflammation, and its impact on macrophage functions in atherosclerotic plaque formation. The potential of sortilin as a therapeutic target is discussed, considering evidence that suggests its modulation could ameliorate atherosclerosis. The review also acknowledges current inconsistencies and gaps in the evidence, calling for more comprehensive patient studies and in-depth mechanistic research. Finally, the article outlines future research directions, focusing on understanding sortilin's specific cellular mechanisms in cardiovascular health, exploring its genetic variability, therapeutic implications, and its broader relevance to other diseases.
CONCLUSION
This review underscores the significance of sortilin as a biomarker and a promising target for therapeutic intervention in cardiovascular pathology, while advocating for continued research to fully unravel its complex role.
PubMed: 38913092
DOI: 10.1186/s43044-024-00512-3 -
Giornale Italiano Di Cardiologia (2006) Jun 2024Coronary calcific disease represents one of the main challenges for the interventional cardiologist, for whom optimal lesion preparation and percutaneous coronary... (Review)
Review
Coronary calcific disease represents one of the main challenges for the interventional cardiologist, for whom optimal lesion preparation and percutaneous coronary intervention optimization are paramount for correct management. In this perspective, intravascular imaging using optical coherence tomography (OCT) is becoming an increasingly indispensable tool. This work aims to provide a detailed overview of the complexity of calcified lesions, first analyzing their various morphologies and their clinical impact: spotty calcium seems to be more present in plaques at higher risk of destabilization, while diffuse calcification is typical of stable coronary stenosis; the eruptive calcific nodule is one of the three culprit lesion phenotypes responsible for acute coronary syndromes.In the second part of this review, the available technologies for the treatment of calcified lesions are described, with the aid of illustrative OCT images. Intravascular lithotripsy causes fractures at various levels of the calcified plaque, both circumferentially and longitudinally, with an improvement in vessel compliance; atherectomy acts by modifying the composition of the plaque with selective action on the hard calcific component. OCT, providing a comprehensive overview of lesion characteristics, can guide in the selection of the most appropriate therapeutic strategy, while also offering important information on the effectiveness of the chosen treatment.
Topics: Humans; Tomography, Optical Coherence; Coronary Artery Disease; Vascular Calcification; Atherectomy, Coronary; Lithotripsy; Percutaneous Coronary Intervention; Plaque, Atherosclerotic
PubMed: 38912742
DOI: 10.1714/4287.42688 -
International Journal of Cardiology.... Aug 2024Longitudinal changes in gut microbiome and inflammation may be involved in the evolution of atherosclerosis after an acute coronary syndrome (ACS). We aimed to...
BACKGROUND
Longitudinal changes in gut microbiome and inflammation may be involved in the evolution of atherosclerosis after an acute coronary syndrome (ACS). We aimed to characterize repeated profiles of gut microbiota and peripheral CD4+ T lymphocytes during the first year after an ACS, and to address their relationship with atherosclerotic plaque changes.
METHODS
Over one year we measured the microbiome, peripheral counts of CD4+ T populations and cytokines in 67 patients shortly after a first ACS. We compared baseline measurements to those of a matched population of 40 chronic patients. A subgroup of 20 ACS patients underwent repeated assessment of fibrous cap thickness (FCT) of a non-culprit lesion.
RESULTS
At admission, ACS patients showed gut dysbiosis compared with the chronic group, which was rapidly reduced and remained low at 1-year. Also, their Th1 and Th2 CD4+ T counts were increased but decreased over time. The CD4+ T counts were related to ongoing changes in gut microbiome. Unsupervised clustering of repeated CD4+ Th0, Th1, Th2, Th17 and Treg counts in ACS patients identified two different cell trajectory patterns, related to cytokines. The group of patients following a high-CD4+ T cell trajectory showed a one-year reduction in their FCT [net effect = -24.2 µm; p = 0.016].
CONCLUSIONS
Patients suffering an ACS show altered profiles of microbiome and systemic inflammation that tend to mimic values of chronic patients after 1-year. However, in one-third of patients, this inflammatory state remains particularly dysregulated. This persistent inflammation is likely related to plaque vulnerability as evident by fibrous cap thinning (Clinical Trial NCT03434483).
PubMed: 38912228
DOI: 10.1016/j.ijcha.2024.101438 -
Journal of Advanced Research Jun 2024Atherosclerosis, traditionally considered a lipid-related disease, is now understood as a chronic inflammatory condition with significant global health implications. (Review)
Review
INTRODUCTION
Atherosclerosis, traditionally considered a lipid-related disease, is now understood as a chronic inflammatory condition with significant global health implications.
OBJECTIVES
This review aims to delve into the complex interactions among immune cells, cytokines, and the inflammatory cascade in atherosclerosis, shedding light on how these elements influence both the initiation and progression of the disease.
METHODS
This review draws on recent clinical research to elucidate the roles of key immune cells, macrophages, T cells, endothelial cells, and clonal hematopoiesis in atherosclerosis development. It focuses on how these cells and process contribute to disease initiation and progression, particularly through inflammation-driven processes that lead to plaque formation and stabilization. Macrophages ingest oxidized low-density lipoprotein (oxLDL), which partially converts to high-density lipoprotein (HDL) or accumulates as lipid droplets, forming foam cells crucial for plaque stability. Additionally, macrophages exhibit diverse phenotypes within plaques, with pro-inflammatory types predominating and others specializing in debris clearance at rupture sites. The involvement of CD4 T and CD8 T cells in these processes promotes inflammatory macrophage states, suppresses vascular smooth muscle cell proliferation, and enhances plaque instability.
RESULTS
The nuanced roles of macrophages, T cells, and the related immune cells within the atherosclerotic microenvironment are explored, revealing insights into the cellular and molecular pathways that fuel inflammation. This review also addresses recent advancements in imaging and biomarker technology that enhance our understanding of disease progression. Moreover, it points out the limitations of current treatment and highlights the potential of emerging anti-inflammatory strategies, including clinical trials for agents such as p38MAPK, tumor necrosis factor α (TNF-α), and IL-1β, their preliminary outcomes, and the promising effects of canakinumab, colchicine, and IL-6R antagonists.
CONCLUSION
This review explores cutting-edge anti-inflammatory interventions, their potential efficacy in preventing and alleviating atherosclerosis, and the role of nanotechnology in delivering drugs more effectively and safely.
PubMed: 38909884
DOI: 10.1016/j.jare.2024.06.016 -
Academic Radiology Jun 2024This study aims to assess whether a radiomics-based nomogram correlates with a higher risk of future cerebro-cardiovascular events in patients with asymptomatic carotid...
RATIONALE AND OBJECTIVES
This study aims to assess whether a radiomics-based nomogram correlates with a higher risk of future cerebro-cardiovascular events in patients with asymptomatic carotid plaques. Additionally, it investigates the nomogram's contribution to the revised Framingham Stroke Risk Profile (rFSRP) for predicting cerebro-cardiovascular risk.
MATERIALS AND METHODS
Predictive models aimed at identifying an increased risk of future cerebro-cardiovascular events were developed and internally validated at one center, then externally validated at two other centers. Survival curves, constructed using the Kaplan-Meier method, were compared through the log-rank test.
RESULTS
This study included a total of 2009 patients (3946 images). The final nomogram was generated using multivariate Cox regression variables, including dyslipidemia, lumen diameter, plaque echogenicity, and ultrasonography (US)-based radiomics risk. The Harrell's concordance index (C-index) for predicting events-free survival (EFS) was 0.708 in the training cohort, 0.574 in the external validation cohort 1, 0.632 in the internal validation cohort, and 0.639 in the external validation cohort 2. The final nomogram showed a significant increase in C-index compared to the clinical, conventional US, and US-based radiomics models (all P < 0.05). Furthermore, the final nomogram-assisted method significantly improved the sensitivity and accuracy of radiologists' visual qualitative score of plaque (both P < 0.001). Among 1058 patients with corresponding 1588 plaque US images classified as low-risk by the rFSRP, 75 (7.1%) patients with corresponding 93 (5.9%) carotid plaque images were appropriately reclassified to the high-risk category by the final nomogram.
CONCLUSION
The radiomics-based nomogram demonstrated accurate prediction of cerebro-cardiovascular events in patients with asymptomatic carotid plaques. It also improved the sensitivity and accuracy of radiologists' visual qualitative score of carotid plaque and enhanced the risk stratification ability of rFSRP.
SUMMARY
The radiomics-based nomogram allowed accurate prediction of cerebro-cardiovascular events, especially ipsilateral ischemic stroke in patients with asymptomatic carotid atherosclerotic plaques.
KEY RESULTS
The radiomics-based nomogram allowed accurate prediction of cerebro-cardiovascular events, especially ipsilateral ischemic stroke in patients with asymptomatic carotid atherosclerotic plaques. The radiomics-based nomogram improved the sensitivity and accuracy of radiologists' visual qualitative score of carotid plaque. The radiomics-based nomogram improved the discrimination of high-risk populations from low-risk populations in asymptomatic patients with carotid atherosclerotic plaques and the risk stratification capability of the rFSRP.
PubMed: 38908923
DOI: 10.1016/j.acra.2024.05.030 -
EBioMedicine Jun 2024Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health.
BACKGROUND
Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health.
METHODS
This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics.
FINDINGS
Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%-10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%-49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%-95%) and 19% (95% CI: 11%-27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks.
INTERPRETATION
This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites.
FUNDING
This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the 'Pioneer' and 'Leading goose' R&D Program of Zhejiang.
PubMed: 38908099
DOI: 10.1016/j.ebiom.2024.105209 -
Medical Engineering & Physics Jul 2024The high mortality rate associated with coronary heart disease has led to state-of-the-art non-invasive methods for cardiac diagnosis including computed tomography and...
BACKGROUND
The high mortality rate associated with coronary heart disease has led to state-of-the-art non-invasive methods for cardiac diagnosis including computed tomography and magnetic resonance imaging. However, stenosis computation and clinical assessment of non-calcified plaques has been very challenging due to their ambiguous intensity response in CT i.e. a significant overlap with surrounding muscle tissues and blood. Accordingly, this research presents an approach for computation of coronary stenosis by investigating cross-sectional lumen behaviour along the length of 3D coronary segments.
METHODS
Non-calcified plaques are characterized by comparatively lower-intensity values with respect to the surrounding. Accordingly, segment-wise orthogonal volume was reconstructed in 3D space using the segmented coronary tree. Subsequently, the cross sectional volumetric data was investigated using proposed CNN-based plaque quantification model and subsequent stenosis grading in clinical context was performed. In the last step, plaque-affected orthogonal volume was further investigated by comparing vessel-wall thickness and lumen area obstruction w.r.t. expert-based annotations to validate the stenosis grading performance of model.
RESULTS
The experimental data consists of clinical CT images obtained from the Rotterdam CT repository leading to 600 coronary segments and subsequent 15786 cross-sectional images. According to the results, the proposed method quantified coronary vessel stenosis i.e. severity of the non-calcified plaque with an overall accuracy of 83%. Moreover, for individual grading, the proposed model show promising results with accuracy equal to 86%, 90% and 79% respectively for severe, moderate and mild stenosis. The stenosis grading performance of the proposed model was further validated by performing lumen-area versus wall-thickness analysis as per annotations of manual experts. The statistical results for lumen area analysis precisely correlates with the quantification performance of the model with a mean deviation of 5% only.
CONCLUSION
The overall results demonstrates capability of the proposed model to grade the vessel stenosis with reasonable accuracy and precision equivalent to human experts.
Topics: Coronary Stenosis; Humans; Plaque, Atherosclerotic; Tomography, X-Ray Computed; Contrast Media; Male
PubMed: 38906576
DOI: 10.1016/j.medengphy.2024.104182