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Frontiers in Immunology 2024Vascular calcification (VC) is considered a common pathological process in various vascular diseases. Accumulating studies have confirmed that VC is involved in the... (Review)
Review
Vascular calcification (VC) is considered a common pathological process in various vascular diseases. Accumulating studies have confirmed that VC is involved in the inflammatory response in heart disease, and SPP1+ macrophages play an important role in this process. In VC, studies have focused on the physiological and pathological functions of macrophages, such as pro-inflammatory or anti-inflammatory cytokines and pro-fibrotic vesicles. Additionally, macrophages and activated lymphocytes highly express SPP1 in atherosclerotic plaques, which promote the formation of fatty streaks and plaque development, and SPP1 is also involved in the calcification process of atherosclerotic plaques that results in heart failure, but the crosstalk between SPP1-mediated immune cells and VC has not been adequately addressed. In this review, we summarize the regulatory effect of SPP1 on VC in T cells, macrophages, and dendritic cells in different organs' VC, which could be a potential therapeutic target for VC.
Topics: Humans; Osteopontin; Vascular Calcification; Animals; Macrophages; Dendritic Cells; T-Lymphocytes; Plaque, Atherosclerotic
PubMed: 38919629
DOI: 10.3389/fimmu.2024.1395596 -
Journal of Inflammation Research 2024The inflammatory response is a pivotal factor in accelerating the progression of atherosclerosis. The high-sensitivity C-reactive protein-to-albumin ratio (CAR) has...
BACKGROUND
The inflammatory response is a pivotal factor in accelerating the progression of atherosclerosis. The high-sensitivity C-reactive protein-to-albumin ratio (CAR) has emerged as a novel marker of systemic inflammation. However, few studies have shown the CAR to be a promising prognostic marker for carotid atherosclerotic disease. This study aimed to analyse the predictive role of the CAR in carotid atherosclerotic disease.
METHODS
This community-based cohort study recruited 2003 participants from the Rose asymptomatic IntraCranial Artery Stenosis (RICAS) study who were free of stroke or transient ischemic attack. Carotid atherosclerotic plaques and their stability were identified via carotid ultrasound. Logistic regression models were utilized to investigate the association between CAR and the presence of carotid atherosclerotic plaques.
RESULTS
The prevalence of carotid atherosclerotic plaques was 38.79% in this study. After adjusting for clinical risk factors, including sex, age, dyslipidemia, hypertension, diabetes mellitus (DM), and smoking and drinking habits, a high CAR-level was independently associated with carotid plaque (odds ratio [OR] of upper: 1.46, 95% confidence interval [CI]: 1.13-1.90, = 0.004; for trend = 0.011). The highest CAR tertile was still significantly associated with carotid plaques among middle-aged (40-64 years) or female participants. Notably, an elevated CAR may be an independent risk factor for vulnerable carotid plaques (OR of upper: 2.06, 95% CI: 1.42-2.98, < 0.001; for trend <0.001).
CONCLUSION
A high CAR may be correlated with a high risk of carotid plaques, particularly among mildly aged adults (40-64 years) or females. Importantly, the CAR may be associated with vulnerable carotid plaques, suggesting that the CAR may be a new indicator for stroke prevention.
PubMed: 38919510
DOI: 10.2147/JIR.S464491 -
BMB Reports Jun 2024Early proatherogenic inflammation constitutes a significant risk factor for atherogenesis development. Despite this, the precise molecular mechanisms driving this...
Early proatherogenic inflammation constitutes a significant risk factor for atherogenesis development. Despite this, the precise molecular mechanisms driving this pathological progression largely remain elusive. Our study unveils a pivotal role for the microRNA miR-328-5p in dampening endothelial inflammation by modulating the stability of JUNB (JunB proto-oncogene). Perturbation of miR-328-5p levels results in heightened monocyte adhesion to endothelial cells and enhanced transendothelial migration, while its overexpression mitigates these inflammatory processes. Furthermore, miR-328-5p hinders macrophage polarization toward the pro-inflammatory M1 phenotype, and exerts a negative influence on atherosclerotic plaque formation in vivo. By pinpointing JUNB as a direct miR-328-5p target, our research underscores the potential of miR-328-5p as a therapeutic target for inflammatory atherosclerosis. Reintroduction of JUNB effectively counteracts the anti-atherosclerotic effects of miR-328-5p, highlighting the promise of pharmacological miR-328-5p targeting in managing inflammatory atherosclerosis.
PubMed: 38919016
DOI: No ID Found -
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 -
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 -
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 -
International Journal of Biological... 2024Shear stress-induced Dickkopf-1 (DKK1) secretion by endothelial cells (ECs) promotes EC dysfunction and accelerates atherosclerosis (AS). However, the paracrine role of...
Shear stress-induced Dickkopf-1 (DKK1) secretion by endothelial cells (ECs) promotes EC dysfunction and accelerates atherosclerosis (AS). However, the paracrine role of endothelial DKK1 in modulating adjacent smooth muscle cells (SMCs) in atherosclerosis remains unclear. This study investigated the role of EC-secreted DKK1 in SMC-derived foam cell formation under shear stress, and . Parallel-plate co-culture flow system was used to explore the cellular communication between ECs and SMCs under shear stress . Endothelium-specific knockout of DKK1 (DKK1/APOE) and endothelium-specific overexpression of DKK1 (DKK1) mice were constructed to investigate the role of endothelial DKK1 in atherosclerosis and SMC-derived foam cell formation . RNA sequencing (RNA-seq) was used to identify the downstream targets of DKK1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot, coimmunoprecipitation (Co-IP) assays and chromatin immunoprecipitation (ChIP) experiments were conducted to explore the underlying regulatory mechanisms. DKK1 is transcriptionally upregulated in ECs under conditions of low shear stress, but not in co-cultured SMCs. However, DKK1 protein in co-cultured SMCs is increased via uptake of low shear stress-induced endothelial DKK1, thereby promoting lipid uptake and foam cell formation in co-cultured SMCs via the post-translational upregulation of scavenger receptor-A (SR-A) verified in parallel-plate co-culture flow system, DKK1 and DKK1 mice. RNA sequencing revealed that DKK1-induced SR-A upregulation in SMCs is dependent on Ubiquitin-specific Protease 53 (USP53), which bound to SR-A via its USP domain and cysteine at position 41, exerting deubiquitination to maintain the stability of the SR-A protein by removing the K48 ubiquitin chain and preventing proteasomal pathway degradation, thereby mediating the effect of DKK1 on lipid uptake in SMCs. Moreover, DKK1 regulates the transcription of USP53 by facilitating the binding of transcription factor CREB to the USP53 promoter. SMC-specific overexpression of USP53 via adeno-associated virus serotype 2 vectors in DKK1/APOE mice reversed the alleviation of atherosclerotic plaque burden, SR-A expression and lipid accumulation in SMCs within plaques resulting from DKK1 deficiency. Our findings demonstrate that, endothelial DKK1, induced by pathological low shear stress, acts as an intercellular mediator, promoted the foam cell formation of SMCs. These results suggest that targeted intervention with endothelial DKK1 may confer beneficial effects on atherosclerosis.
Topics: Animals; Atherosclerosis; Mice; Intercellular Signaling Peptides and Proteins; Foam Cells; Myocytes, Smooth Muscle; Endothelial Cells; Humans; Ubiquitination; Male; Coculture Techniques; Mice, Knockout; Ubiquitin-Specific Proteases; Mice, Inbred C57BL
PubMed: 38904030
DOI: 10.7150/ijbs.91957 -
Frontiers in Medicine 2024[This corrects the article DOI: 10.3389/fmed.2024.1284199.].
[This corrects the article DOI: 10.3389/fmed.2024.1284199.].
PubMed: 38895189
DOI: 10.3389/fmed.2024.1416622 -
Diagnostics (Basel, Switzerland) May 2024The aim of the study was to assess the relationship between the presence of atherosclerotic lesions in the carotid arteries detected by ultrasound and the occurrence of...
The aim of the study was to assess the relationship between the presence of atherosclerotic lesions in the carotid arteries detected by ultrasound and the occurrence of atherosclerosis in the coronary arteries determined by computed tomography (CT) in patients with arterial hypertension (HTA). A total of 83 patients with HTA were qualified for the study (age: 71.3 ± 8.5 years). All subjects underwent carotid arteries ultrasound and coronary arteries CT. The carotid plaque score was assessed using ultrasound. The studied group was divided into two subgroups: a subgroup with the carotid plaque score ≤ 1 (A) and a subgroup with carotid plaque score ≥2 (B). Coronary arteries CT assessed coronary artery calcium score (CACS) and degree of coronary stenosis based on CAD-RADS. In subgroup B, a significantly higher CACS (411.3 ± 70.1 vs. 93.5 ± 31.8) and significantly higher grade in the CAD-RADS classification were demonstrated than in subgroup A (CAD-RADS ≥ 3: 21.8 vs. 6.0%). The regression analysis showed that carotid plaque score and age are independent risk factors for the severity of atherosclerotic lesions in the coronary arteries. In summary, ultrasound assessment of the carotid plaque score in patients with HTA could be considered as surrogate indicator of the risk and severity of atherosclerotic changes in the coronary arteries, but further studies are necessary to corroborate these results.
PubMed: 38893628
DOI: 10.3390/diagnostics14111101