Atherosclerotic Plaque Progression Research Articles

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.

Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn.

Matrix metalloproteinase 13 (MMP13) is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens, modifying protein structures and regulating inflammatory responses, but its role in deep vein thrombosis (DVT) has not been determined. The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT. We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT. After screening genes possibly related to MMP13 in DVT mice, the expression levels of candidate genes in human umbilical vein endothelial cells (HUVECs) and the venous wall were evaluated. The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro. Among the differentially expressed genes, interleukin 1 beta, podoplanin (Pdpn), and factor VIII von Willebrand factor (F8VWF) were selected for analysis in mice. When MMP13 was inhibited, the expression level of PDPN decreased significantly in vitro. In HUVECs, overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation, while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation. Inhibiting the expression of MMP13 could reduce the burden of DVT in mice. The mechanism involves downregulating the expression of Pdpn through MMP13, which could provide a novel gene target for DVT diagnosis and treatment.

CNP Ameliorates Macrophage Inflammatory Response and Atherosclerosis.

CNP (C-type natriuretic peptide), an endogenous short peptide in the natriuretic peptide family, has emerged as an important regulator to govern vascular homeostasis. However, its role in the development of atherosclerosis remains unclear. This study aimed to investigate the impact of CNP on the progression of atherosclerotic plaques and elucidate its underlying mechanisms. Plasma CNP levels were measured in patients with acute coronary syndrome. The potential atheroprotective role of CNP was evaluated in apolipoprotein E-deficient (ApoE-/-) mice through CNP supplementation via osmotic pumps, genetic overexpression, or LCZ696 administration. Various functional experiments involving CNP treatment were performed on primary macrophages derived from wild-type and CD36 (cluster of differentiation 36) knockout mice. Proteomics and multiple biochemical analyses were conducted to unravel the underlying mechanism. We observed a negative correlation between plasma CNP concentration and the burden of coronary atherosclerosis in patients. In early atherosclerotic plaques, CNP predominantly accumulated in macrophages but significantly decreased in advanced plaques. Supplementing CNP via osmotic pumps or genetic overexpression ameliorated atherosclerotic plaque formation and enhanced plaque stability in ApoE-/- mice. CNP promoted an anti-inflammatory macrophage phenotype and efferocytosis and reduced foam cell formation and necroptosis. Mechanistically, we found that CNP could accelerate HIF-1α (hypoxia-inducible factor 1-alpha) degradation in macrophages by enhancing the interaction between PHD (prolyl hydroxylase domain-containing protein) 2 and HIF-1α. Furthermore, we observed that CD36 bound to CNP and mediated its endocytosis in macrophages. Moreover, we demonstrated that the administration of LCZ696, an orally bioavailable drug recently approved for treating chronic heart failure with reduced ejection fraction, could amplify the bioactivity of CNP and ameliorate atherosclerotic plaque formation. Our study reveals that CNP enhanced plaque stability and alleviated macrophage inflammatory responses by promoting HIF-1α degradation, suggesting a novel atheroprotective role of CNP. Enhancing CNP bioactivity may offer a novel pharmacological strategy for treating related diseases.

FTO Stabilizes MIS12 to Inhibit Vascular Smooth Muscle Cell Senescence in Atherosclerotic Plaque.

Atherosclerosis is the main cause of atherosclerotic cardiovascular disease (CVD). Here, we aimed to uncover the role and mechanisms of fat mass and obesity-associated genes (FTO) in the regulation of vascular smooth muscle cell (VSMC) senescence in atherosclerotic plaques. ApoE-/- mice fed a high-fat diet (HFD) were used to establish an atherosclerotic animal model. Immunohistochemistry, and the staining of hematoxylin-eosin, Oil Red O, Sirius red, and Masson were performed to confirm the role of FTO in atherosclerosis in vivo. Subsequently, FTO expression in primary VSMCs is either upregulated or downregulated. Oxidized low-density lipoprotein (ox-LDL) was used to treat VSMCs, followed by EdU staining, flow cytometry, senescence-associated β-galactosidase (SA-β-gal) staining, immunofluorescence, telomere detection, RT-qPCR, and Western blotting to determine the molecular mechanisms by which FTO inhibits VSMC senescence. Decreased FTO expression was observed in progressive atherosclerotic plaques of ApoE-/- mice fed with HFD. FTO upregulation inhibits atherosclerotic lesions in mice. FTO inhibits VSMC aging in atherosclerotic plaques by helping VSMC withstand ox-LDL-induced cell cycle arrest and senescence. This process is achieved by stabilizing the MIS12 protein in VSMC through a proteasome-mediated pathway. FTO inhibits VSMC senescence and subsequently slows the progression of atherosclerotic plaques by stabilizing the MIS12 protein.

The Influence of Coronavirus Infection on the Results of Percutaneous Coronary Intervention in Patients with Coronary Artery Disease

Objective — to determine the impact of coronavirus infection incidence on the post-procedural condition of patients after percutaneous coronary intervention (PCI). Materials and methods. This single-centre study was conducted at the «Ukrainian Children’s Cardiac Center, Clinic for Adults» from June 1, 2020, to December 31, 2021. A total of 158 patients participated, of whom 78 had a history of COVID-19 infection and 80 did not, all with stable obstructive coronary artery disease (CAD). All patients underwent PCI, and their long-term outcomes were evaluated within a 6-month period. The study endpoints included repeated myocardial revascularization (defined as narrowing of the stented lumen by more than 70 % in diameter or acute stent thrombosis) and an assessment of CAD progres­sion (formation or progression of atherosclerotic plaques compared to baseline coronary angio­graphy). Results and discussion. The frequency of repeated coronary angio in the first 6 months after PCI due to tension angina or acute coronary syndrome was equal to 10 (12.8 %) patients in the COVID-19 +-group and 3 (3.8 %) cases in the COVID-19 — –group (p < 0.05). According to the study data, patients with coronavirus infection tended to reach endpoints more quickly during the 6-month follow-up, in contrast to patients who did not have the incidence of COVID-19 during the same period. The frequency of repeated PCI within 6 months after the primary PCI in the group of patients with previous PCI was higher — 8 cases out of 78 patients compared to patients in the second group who did not suffer from COVID-19 in the first 6 months after the initial PCI (2 cases out of 80, c2 = 4 .0, p = 0.045). Conclusions. Patients with a mild and moderate course of coronavirus infection and existing stable coronary heart disease with atherosclerotic lesions of the coronary arteries were more likely to undergo repeat PCI within 6 months of the initial PCI. The most common causes of repeat PCI in patients with previous COVID-19 were thrombosis and restenosis of the stent, as well as progression of stenosis at a site other than the location of the previous PCI.

Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.

Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear. High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis. The differentially expression and activity of Gsα were analyzed by immunofluorescence and cAMP measurements. Macrophage-specific Gsα knockout (Mac-GsαKO) mice were generated to study the effect on atherosclerosis. The role of Gsα was determined by transplanting bone marrow and performing assays for foam cell formation, Dil-ox-LDL (oxidized low-density lipoprotein) uptake, chromatin immunoprecipitation, and luciferase reporter assays. ScRNA-seq showed elevated Gnas in atherosclerotic mouse aorta's cholesterol metabolism macrophage cluster, while bulk sequencing confirmed increased GNAS expression in human plaque macrophage content. A significant upregulation of Gsα and active Gsα occurred in macrophages from human and mouse plaques. Ox-LDL could translocate Gsα from macrophage lipid rafts in short-term and promote Gnas transcription through ERK1/2 activation and C/EBPβ phosphorylation via oxidative stress in long-term. Atherosclerotic lesions from Mac-GsαKO mice displayed decreased lipid deposition compared with those from control mice. Additionally, Gsα deficiency alleviated lipid uptake and foam cell formation. Mechanistically, Gsα increased the levels of cAMP and transcriptional activity of the cAMP response element binding protein, which resulted in increased expression of CD36 and SR-A1. In the translational experiments, inhibiting Gsα activation with suramin or cpGN13 reduced lipid uptake, foam cell formation, and the progression of atherosclerotic plaques in mice in vivo. Gsα activation is enhanced during atherosclerotic progression and increases lipid uptake and foam cell formation. The genetic or chemical inactivation of Gsα inhibit the development of atherosclerosis in mice, suggesting that drugs targeting Gsα may be useful in the treatment of atherosclerosis.

Comprehensive analysis identifies crucial genes associated with immune cells mediating progression of carotid atherosclerotic plaque.

Carotid atherosclerosis is prone to rupture and cause ischemic stroke in advanced stages of development. Our research aims to provide markers for the progression of atherosclerosis and potential targets for its treatment. We performed a thorough analysis using various techniques including DEGs, GO/KEGG, xCell, WGCNA, GSEA, and other methods. The gene expression omnibus datasets GSE28829 and GSE43292 were utilized for this comprehensive analysis. The validation datasets employed in this study consisted of GSE41571 and GSE120521 datasets. Finally, we validated PLEK by immunohistochemistry staining in clinical samples. Using the WGCNA technique, we discovered 636 differentially expressed genes (DEGs) and obtained 12 co-expression modules. Additionally, we discovered two modules that were specifically associated with atherosclerotic plaque. A total of 330 genes that were both present in DEGs and WGCNA results were used to create a protein-protein network in Cytoscape. We used four different algorithms to get the top 10 genes and finally got 6 overlapped genes (TYROBP, ITGB2, ITGAM, PLEK, LCP2, CD86), which are identified by GSE41571 and GSE120521 datasets. Interestingly, the area under curves (AUC) of PLEK is 0.833. Besides, we found PLEK is strongly positively correlated with most lymphocytes and myeloid cells, especially monocytes and macrophages, and negatively correlated with most stromal cells (e.g, neurons, myocytes, and fibroblasts). The expression of PLEK were consistent with the immunohistochemistry results. Six genes (TYROBP, ITGB2, ITGAM, PLEK, LCP2, CD86) were found to be connected with carotid atherosclerotic plaques and PLEK may be an important biomarker and a potential therapeutic target.

7-year follow-up atherosclerotic plaque progression in patients with antiphospholipid syndrome versus diabetes mellitus and healthy controls.

Patients with antiphospholipid syndrome (APS) carry a substantial burden of cardiovascular disease and subclinical atherosclerosis. We aimed to assess a 7-year follow-up atherosclerotic plaque progression in APS patients vs diabetes mellitus (DM) and healthy controls (HC). Eighty-six patients with thrombotic APS, 86 with DM and 86 HC (all age- and sex-matched) who underwent a baseline ultrasound of carotid and femoral arteries were invited for a 7-year follow-up ultrasonography examination. We compared atherosclerosis progression among the three groups and examined determinants of plaque progression in APS patients. Sixty-four APS patients (75% females, 43.8% with primary APS), 58 patients with DM and 66 HC were included in the 7-year ultrasound re-evaluation. New plaque was detected in 51.6%, 36.2% and 25.8% of APS, DM and HC subjects, respectively. After adjusting for traditional cardiovascular risk factors (CVRFs) and baseline plaque presence, APS patients showed a 3-fold (OR = 3.07, p= 0.007) higher risk for atherosclerosis progression vs HC and 2-fold (OR = 2.25, p= 0.047) higher risk than DM patients. In multivariate analysis in the APS group, plaque progression was independently associated with systemic lupus erythematosus (SLE) co-existence (OR = 7.78, p= 0.005) and number of CVRFs (OR = 3.02, p= 0.002), after adjusting for disease-related parameters and CVRF-related medications. Sustained low-density lipoprotein target attainment reduced plaque progression risk (OR = 0.34, p= 0.021). Half of APS patients develop new atherosclerotic plaques over a 7-year follow-up, having a three-times higher risk vs HC. Concomitant SLE and number of traditional CVRFs are associated with plaque progression, supporting the need for thorough CVRF assessment and control.

Non-lamellar lyotropic liquid crystalline nanoparticles as nanocarriers for enhanced drug encapsulation of atorvastatin calcium and proanthocyanidins

Atorvastatin calcium (ATV) and proanthocyanidins (PAC) have a strong antioxidant activity, that can benefit to reduce the atherosclerotic plaque progression. Unfortunately, the bioavailability of ATV is greatly reduced due to its limited drug solubility while the PAC drug is unstable upon exposure to the atmospheric oxygen. Herein, the lyotropic liquid crystalline nanoparticles (LLCNPs) constructed by a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem) at different weight ratios were used to encapsulate the hydrophobic ATV and hydrophilic PAC. The LLCNPs were further characterized by small-angle X-ray scattering and dynamic light scattering. Depending on the lipid composition, the systems have a size range of 140–190 nm and were able to encapsulate both drugs in the range of 90–100%. Upon increasing the citrem content of drug-loaded LLCNPs, the hexosomes (H2) was completely transformed to an emulsified inverse micellar (L2). The optimum encapsulation efficiency (EE) of ATV and PAC were obtained in citrem/SPC weight ratio 4:1 (L2) and 1:1 (H2), respectively. There was a substantial change in the mean size and PDI of the nanoparticles upon 30 days of storage with the ATV-loaded LLCNPs exhibiting greater colloidal instability than PAC-loaded LLCNPs. The biphasic released pattern (burst released at the initial stage followed by the sustained released at the later stage) was perceived in ATV formulation, while the burst drug released pattern was observed in PAC formulations that could be attributed by its internal H2 structure. Interestingly, the cytokine studies showed that the PAC-LLCNPs promisingly up regulate the expressions of tumor necrosis factor-alpha (TNF-α) better than the drug-free and ATV-loaded LLCNPs samples. The structural tunability of citrem/SPC nanoparticles and their effect on physicochemical characteristic, biological activities and potential as an alternative drug delivery platform in the treatment of atherosclerosis are discussed.

Muscone inhibits the progression of atherosclerotic plaques in mice aorta by inhibiting the NF-κB/p65 pathway

Atherosclerosis (AS) is considered to be one of the main pathogenic factors of coronary heart disease, cerebral infarction and peripheral vascular disease. Oxidative stress and inflammation run through the occurrence and development of atherosclerosis and related cardiovascular events. Muscone is a natural extract of deer musk and also the main physiological active substance of musk. This study investigated the impact of muscone on atherosclerosis. ApoE−/− mice were used to establised AS model and injected with low-dose (4 mg/kg/day) or high-dose (8 mg/kg/day) of muscone intraperitoneally for 4 weeks. Then aortic tissues were collected, and pathological sections of the aorta were prepared for oil red staining, HE and masson staining. The changes of MDA, SOD, VCAM-1, NF-κB, and TNF-α were observed by Western blotting or immunofluorescence staining. The results showed that high-dose muscone could effectively reduce the plaque area/aortic root area and relative atherosclerotic area, reduce the collagen composition in plaque tissue. In addition, we also found that high-dose muscone can effectively increase MDA level, reduce the level of SOD, and inhibit the expression of VCAM-1, NF-κB/p65, TNF-α in arterial plaques. Our results indicate that the administration of muscone has the benefit of inhibiting atherosclerosis. The potential mechanisms may be associated with antioxidant effect and inhibition of inflammatory reaction in arterial plaques. With the increasing understanding of the relationship between muscone and atherosclerosis, muscone has high potential value as a new drug to treat atherosclerosis.

Gelatin-decorated Graphene oxide: A nanocarrier for delivering pH-responsive drug for improving therapeutic efficacy against atherosclerotic plaque

The progressive inflammatory disease atherosclerosis promotes myocardial infarction, stroke, and heart attack. Anti-inflammatory drugs treat severe atherosclerosis. They are inadequate bioavailability and cause adverse effects at higher doses. A new nanomaterial coupled pH-apperceptive drug delivery system for atherosclerotic plaque is outlined here. We have synthesized a Graphene Oxide-Gelatin-Atorvastatin (GO-Gel-ATR) nanodrug characterized by spectroscopic and imaging techniques. The encapsulation efficiency of GO-Gel-ATR (79.2%) in the loading process is observed to be better than GO-ATR (66.8%). The internal milieu of the plaque cells has a pH of 6.8. The GO-Gel-ATR displays sustained and cumulative release profile at pH 6.8 compared to ATR and GO-ATR. Our proposed nanocomposite demonstrated high cytocompatibility up to 100μg/mL in foam cells induced by Oxidized-Low Density Lipoprotein (Ox-LDL) and Lipopolysaccharides (LPS) compared to normal macrophages for 24 and 48 h. The uptake efficacy of the nanodrugs is shown to be enhanced in foam cells compared to normal macrophage. Oil red O staining of foam cells with and without drugs confirmed therapeutic efficacy. Foam cells treated with nanocomposite had more lipids efflux than ATR. The finding of the in-vitro study reveals that the GO-Gel-ATR nanocomposite carriers have the potential to deliver anti-atherosclerotic drugs effectively and inhibit atherosclerotic plaque progression.

Immunological perspectives on atherosclerotic plaque formation and progression.

Atherosclerosis serves as the primary catalyst for numerous cardiovascular diseases. Growing evidence suggests that the immune response is involved in every stage of atherosclerotic plaque evolution. Rapid, but not specific, innate immune arms, including neutrophils, monocytes/macrophages, dendritic cells (DCs) and other innate immune cells, as well as pattern-recognition receptors and various inflammatory mediators, contribute to atherogenesis. The specific adaptive immune response, governed by T cells and B cells, antibodies, and immunomodulatory cytokines potently regulates disease activity and progression. In the inflammatory microenvironment, the heterogeneity of leukocyte subpopulations plays a very important regulatory role in plaque evolution. With advances in experimental techniques, the fine mechanisms of immune system involvement in atherosclerotic plaque evolution are becoming known. In this review, we examine the critical immune responses involved in atherosclerotic plaque evolution, in particular, looking at atherosclerosis from the perspective of evolutionary immunobiology. A comprehensive understanding of the interplay between plaque evolution and plaque immunity provides clues for strategically combating atherosclerosis.

Progression Of Atherosclerotic Plaque Determined By Computed Tomography Angiography: A Practical CCTA-based SCORE

Progression Of Atherosclerotic Plaque Determined By Computed Tomography Angiography: A Practical CCTA-based SCORE

Natto consumption suppresses atherosclerotic plaque progression in LDL receptor-deficient mice transplanted with iRFP-expressing hematopoietic cells

Natto, known for its high vitamin K content, has been demonstrated to suppress atherosclerosis in large-scale clinical trials through a yet-unknown mechanism. In this study, we used a previously reported mouse model, transplanting the bone marrow of mice expressing infra-red fluorescent protein (iRFP) into LDLR-deficient mice, allowing unique and non-invasive observation of foam cells expressing iRFP in atherosclerotic lesions. Using 3 natto strains, we meticulously examined the effects of varying vitamin K levels on atherosclerosis in these mice. Notably, high vitamin K natto significantly reduced aortic staining and iRFP fluorescence, indicative of decreased atherosclerosis. Furthermore, mice administered natto showed changes in gut microbiota, including an increase in natto bacteria within the cecum, and a significant reduction in serum CCL2 expression. In experiments with LPS-stimulated macrophages, adding natto decreased CCL2 expression and increased anti-inflammatory cytokine IL-10 expression. This suggests that natto inhibits atherosclerosis through suppression of intestinal inflammation and reduced CCL2 expression in macrophages.

Role of periodontal pathogens in atherosclerotic plaque development and progression: An overview.

Atherosclerosis is a progressive disease marked by the accumulation of lipids and fibrous components in the large arteries. It is one of the primary causes of heart disease and stroke. Periodontal diseases encompass conditions like gingivitis and periodontitis, which are multifactorial diseases associated with dysbiotic plaque biofilms that trigger an immune-inflammatory host response, eventually resulting in the destruction of periodontal tissues. Links between periodontal disease and atherosclerosis may be based on direct invasion of periodontal pathogens or inflammatory mechanisms triggered by bacteria related to periodontal lesions, locally or systemically, that may impact the initiation of the atherosclerotic lesion. The presence of periodontal pathogens within an atheromatous lesion implies hematogenous dissemination. The invasion of atheroma by periodontal pathogens results in changes in the proatherogenic and proinflammatory properties of endothelial cells, leading to endothelial dysfunction, which is a hallmark of atherosclerosis. Clinical and epidemiological studies have offered sufficient evidence of periodontitis having an adverse effect on systemic health, including atherosclerosis; however, a direct causal effect has not yet been proved. This review aims to analyse scientific results regarding the mechanism by which periodontal pathogens may cause atherosclerosis as well as to describe the role of Porphyromonas gingivalis in atherosclerotic plaque development and progression.

Unveiling the role of ABI3 and hub senescence-related genes in macrophage senescence for atherosclerotic plaque progression

BackgroundAtherosclerosis, characterized by abnormal arterial lipid deposition, is an age-dependent inflammatory disease and contributes to elevated morbidity and mortality. Senescent foamy macrophages are considered to be deleterious at all stages of atherosclerosis, while the underlying mechanisms remain largely unknown. In this study, we aimed to explore the senescence-related genes in macrophages diagnosis for atherosclerotic plaque progression.MethodsThe atherosclerosis-related datasets were retrieved from the Gene Expression Omnibus (GEO) database, and cellular senescence-associated genes were acquired from the CellAge database. R package Limma was used to screen out the differentially expressed senescence-related genes (DE-SRGs), and then three machine learning algorithms were applied to determine the hub DE-SRGs. Next, we established a nomogram model to further confirm the clinical significance of hub DE-SRGs. Finally, we validated the expression of hub SRG ABI3 by Sc-RNA seq analysis and explored the underlying mechanism of ABI3 in THP-1-derived macrophages and mouse atherosclerotic lesions.ResultsA total of 15 DE-SRGs were identified in macrophage-rich plaques, with five hub DE-SRGs (ABI3, CAV1, NINJ1, Nox4 and YAP1) were further screened using three machine learning algorithms. Subsequently, a nomogram predictive model confirmed the high validity of the five hub DE-SRGs for evaluating atherosclerotic plaque progression. Further, the ABI3 expression was upregulated in macrophages of advanced plaques and senescent THP-1-derived macrophages, which was consistent with the bioinformatics analysis. ABI3 knockdown abolished macrophage senescence, and the NF-κB signaling pathway contributed to ABI3-mediated macrophage senescence.ConclusionWe identified five cellular senescence-associated genes for atherogenesis progression and unveiled that ABI3 might promote macrophage senescence via activation of the NF-κB pathway in atherogenesis progression, which proposes new preventive and therapeutic strategies of senolytic agents for atherosclerosis.

High-resolution magnetic resonance imaging investigation of the connection between the triglyceride-glucose index and intracranial arterial remodeling: a retrospective cross-sectional study.

Insulin resistance (IR) is associated with atherosclerotic plaque progression and the occurrence of stroke, with the triglyceride-glucose (TyG) index serving as a surrogate indicator. The present study aimed to investigate the association between TyG index levels and intracranial arterial remodeling in patients with acute ischemic stroke (AIS). Patients with AIS who visited the Neurology Department of the Second Hospital of Hebei Medical University and underwent high-resolution magnetic resonance imaging (HR-MRI) between September 2018 and October 2021 were enrolled. A total of 123 patients were finally included in the study, with 81 excluded. The TyG index levels were measured, and the characteristics of intracranial atherosclerotic stenosis (ICAS) plaques were evaluated using HR-MRI. A logistic regression model was employed to analyze the relationship between TyG index levels and remodeling mode. Patients were divided into two groups, positive remodeling (PR) and non-positive remodeling (non-PR), based on the remodeling index (RI). Patients in the PR group had a higher TyG index than those in the non-PR group {median [interquartile range (IQR)]: 9.11 (8.82-9.51) vs. 8.72 (8.30-9.23), P<0.001}. After adjusting factors such as age and gender, the TyG index was found to be significantly correlated with intracranial arterial PR [odds ratio (OR): 3.169, 95% confidence interval (CI): 1.327-7.569, P=0.009]. In non-diabetes mellitus (DM) patients, the TyG index level in the PR group was significantly higher than that in the non-PR group (8.95±0.42 vs. 8.50±0.45, P<0.001), whereas there was no such difference in patients with DM. TyG index was correlated with intracranial vessel PR, indicating that the TyG index level may be a useful marker for predicting intracranial vessel PR.

The improvement of endothelial function by inhibition of platelet activity using acetylsalicylic acid in patients with arterial hypertension

In accordance with modern ideas about the pathogenesis of thrombotic complications of cardiovascular diseases (myocardial infarction, stroke), it should be noted that platelets and platelet humoral factors play a key role in the development of thrombosis. Activated platelets are able to activate both endotheliocytes and pro-inflammatory cells - monocytes/macrophages, which take a direct part in the formation and progression of atherosclerotic plaque. The purpose of the study is to investigate the potential improvement of endothelial function through the inhibition of platelet activity using acetylsalicylic acid in patients with arterial hypertension and established atherosclerotic cardiovascular diseases. Materials and methods. We enrolled 41 patients with arterial hypertension and established atherosclerotic cardiovascular diseases in our study. The participants were divided into two groups. Group 1 comprised 20 patients who were already taking acetylsalicylic acid (ASA) before the study, while Group 2 consisted of 21 patients who had not received ASA before participating. During the 6-month study period, patients from both groups received ASA (75 mg once a day) as part of their basic therapy, which included antihypertensive and statin therapy. Platelet activity was assessed in all patients before the study and at the final stage by determining the expression of glycoproteins GPIIb-IIIa and P-selectin on their surface. Additionally, the content of endothelial progenitor cells (phenotype CD45-CD31+CD133+) and desquamated endothelial cells (phenotype CD45-CD31+CD133-) in the blood was analyzed using flow cytometry. ELISA was employed to measure the content of C-reactive protein, cytokines TNF-α and IL-10, as well as asymmetric dimethylarginine (ADMA) in the blood. Finally, all patients underwent a test with flow-dependent vasodilation of the brachial artery. Results. In patients who did not receive ASA before the study, there was a higher level of platelet activity in peripheral blood flow, along with signs of more pronounced endothelial dysfunction compared to those who received it. After 6 months of taking ASA alongside standard antihypertensive therapy, the activation level of circulating blood platelets decreased in both groups. Specifically, in patients of group 1, the expression level of CD41 (GPIIb) decreased by 31.8 % (p &lt; 0.01), and CD61 (GPIIIa) decreased by 15.2 % (p &lt; 0.01). In group 2 patients, the suppression of platelet activity was even more pronounced, with the expression level of CD41 (GPIIb) decreasing by 55.2 % (p &lt; 0.001), and CD61 (GPIIIa) decreasing by 27.5 % (p &lt; 0.05). Furthermore, in patients of group 1, the percentage of platelets carrying P-selectin on the surface decreased by 78.1 % (p &lt; 0.01). In group 2, the number of such platelets also significantly decreased by 42.5 % (p &lt; 0.05). The number of progenitor cells of endothelial cells in the circulating blood increased significantly in both groups, showing a 3-fold increase in patients of group 1 (p &lt; 0.001) and a 2.3-fold increase in patients of group 2 ( p&lt; 0.001). In patients of both groups, a significant 2-fold increase in the endothelium-dependent vasodilatation index was observed (p &lt; 0.01). At the end of the study, there was a decrease in the blood level of CRP by 12.2 % and 18.8 %, and pro-inflammatory cytokine TNF-α decreased by 50% and 57 %, respectively, in patients of groups 1 and 2 (p &lt; 0.001). Conclusion. The reduction in blood platelet activity triggered by ASA in patients with arterial hypertension and atherosclerotic cardiovascular diseases was associated with notable alterations in the intensity of systemic inflammation and the restoration of endothelial functions. These findings suggest a potential therapeutic role for ASA in modulating both platelet function and endothelial health in individuals with these conditions.

Preventive Therapies in Peripheral Arterial Disease.

Atherosclerosis, while initially deemed a bland proliferative process, is now recognized as a multifactorial-lipoprotein-mediated inflammation-driven pathway. With the rising incidence of atherosclerotic disease of the lower extremity arteries, the healthcare burden and clinical morbidity and mortality due to peripheral artery disease (PAD) are currently escalating. With a healthcare cost burden of over 21 billion USD and 200 million patients afflicted worldwide, accurate knowledge regarding the pathophysiology, presentation, and diagnosis of the disease is crucial. The role of lipoproteins and their remnants in atherosclerotic vessel occlusion and plaque formation and progression has been long established. This review paper discusses the epidemiology, pathophysiology, and presentation of PAD. PAD has been repeatedly noted to portend to poor cardiovascular and limb outcomes. We discuss major therapeutic avenues for the prevention of major cardiovascular adverse events and major limb adverse events in patients with PAD.

Relationship of Soluble Lectin-Like Low-Density Lipoprotein Receptor-1 (sLOX-1) With Inflammation and Coronary Plaque Progression in Psoriasis.

Psoriasis is a chronic inflammatory condition associated with coronary artery disease risk. Uptake of oxidized low-density lipoprotein by the lectin-like low-density lipoprotein receptor-1 triggers release of the soluble extracellular domain of the receptor (sLOX-1). We sought to characterize the relationship between sLOX-1, inflammation, and coronary plaque progression in psoriasis. A total of 327 patients with psoriasis had serum sLOX-1 levels measured at baseline by an ELISA-based assay. Stratification by high-sensitivity C-reactive protein ≥4.0 mg/L (quartile 4), identified 81 participants who had coronary plaque phenotyping at baseline and were followed longitudinally by coronary computed tomography angiography. Subjects within high-sensitivity C-reactive protein quartile 4 were middle-aged (51.47±12.62 years), predominantly men (54.3%) with moderate psoriasis disease severity (6.60 [interquartile range, 3.30-13.40]). In the study cohort, participants with sLOX-1 above the median displayed increased vulnerable coronary plaque features. At baseline, sLOX-1 was associated with total burden (rho=0.296; P=0.01), noncalcified burden (rho=0.286; P=0.02), fibro-fatty burden (rho=0.346; P=0.004), and necrotic burden (rho=0.394; P=0.002). A strong relationship between sLOX-1, noncalcified burden (β=0.19; P=0.03), and fibro-fatty burden (β=0.29; P=0.003) was found in fully adjusted models at baseline and 1- and 4-year follow-up. Finally, coronary plaque features progressed over 1 year regardless of biologic or systemic treatment in subjects with high sLOX-1. Patients with psoriasis with both high sLOX-1 and high-sensitivity C-reactive protein levels have increased coronary plaque burden associated with atherosclerotic plaque progression independent of biologic and systemic treatment. Thus, sLOX-1 might be considered as a promising marker in coronary artery disease risk estimation beyond traditional risk factors. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01778569.