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Journal of Vascular Surgery Jun 2024Carotid plaque vulnerability is a significant factor in the risk of cardio-cerebrovascular events, with intraplaque neovascularization (IPN) being a crucial...
OBJECTIVE
Carotid plaque vulnerability is a significant factor in the risk of cardio-cerebrovascular events, with intraplaque neovascularization (IPN) being a crucial characteristic of plaque vulnerability. This study investigates the value of ultrasound vector flow imaging (V-Flow) for measuring carotid plaque wall shear stress (WSS) in predicting the extent of IPN.
METHODS
We enrolled 140 patients into three groups: 53 in the plaque group (72 plaques), 23 in the stenosis group (27 plaques), and 64 in the control group. V-Flow was employed to measure WSS parameters, including the average WSS (WSS Mean) and the maximum WSS (WSS Max), across three plaque locations: mid-upstream, maximum thickness, and mid-downstream. Contrast-enhanced ultrasound (CEUS) was utilized in 76 patients to analyze IPN and its correlation with WSS parameters.
RESULTS
1. WSS Max in the stenosis group was significantly higher than that in the control and plaque groups at the maximum thickness part (p < 0.05); WSS Mean in the stenosis group was significantly lower than that in the control group at the mid-upstream and mid-downstream segments (p < 0.05); and WSS Mean in the plaque group was significantly lower than that of the control group at all three locations (p < 0.05). 2. CEUS revealed that plaques with neovascularization enhancement exhibited significantly higher WSS values (p < 0.05), with a positive correlation between WSS parameters and IPN enhancement grades, particularly WSS Max at the thickest part (r = 0.508). 3. ROC curve analysis of WSS parameters for evaluating IPN showed that the efficacy of WSS Max in evaluating IPN was better than that of WSS Mean (p < 0.05), with an AUC of 0.7762, 0.6973; 95% CI of 0.725 - 0.822, 0.642 - 0.749, respectively; Cut-off was 4.57 Pa, 1.12 Pa; sensitivity was 74.03%, 63.64%; specificity was 75.00%, 68.18%.
CONCLUSIONS
V-Flow effectively measures WSS in carotid plaques. WSS Max provides a promising metric for assessing IPN, offering potential insights into plaque characteristics and showing some potential in predicting plaque vulnerability.
PubMed: 38925348
DOI: 10.1016/j.jvs.2024.06.024 -
Arteriosclerosis, Thrombosis, and... Jul 2024
Topics: Humans; Plaque, Atherosclerotic; Atherosclerosis; Rupture, Spontaneous; Disease Progression; Animals
PubMed: 38924440
DOI: 10.1161/ATVBAHA.124.319396 -
European Journal of Clinical... Jun 2024Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a novel class of drugs with cardioprotective effects through their lipid-lowering... (Review)
Review
BACKGROUND
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a novel class of drugs with cardioprotective effects through their lipid-lowering effects.
OBJECTIVE
This review aims to discuss existing and novel strategies of PCSK9 inhibition, providing an overview of established randomized controlled trials and ongoing outcome trials that assess the efficacy and long-term safety of PCSK9 inhibitors. It also explores the evolving role of PCSK9 beyond lipid metabolism and outlines the pleiotropic actions of PCSK9 inhibition in various disorders and future directions including novel strategies to target PCSK9.
CONCLUSION
PCSK9 inhibition shows promise not only in lipid metabolism but also in other disease processes, including atherosclerotic plaque remodeling, acute coronary syndrome, stroke, inflammation, and immune response.
PubMed: 38924090
DOI: 10.1111/eci.14272 -
European Journal of Clinical... Jun 2024Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in lipid metabolism, but recent evidence suggests that it may have broader... (Review)
Review
BACKGROUND
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in lipid metabolism, but recent evidence suggests that it may have broader implications due to its diverse tissue expression.
OBJECTIVE
This review aims to explore the multifaceted functions of PCSK9, highlighting its pro-atherosclerotic effects, including its impact on circulating lipoprotein variables, non-low-density lipoprotein receptors, and various cell types involved in atherosclerotic plaque development.
CONCLUSIONS
PCSK9 exhibits diverse roles beyond lipid metabolism, potentially contributing to atherosclerosis through multiple pathways. Understanding these mechanisms could offer new insights into therapeutic strategies targeting PCSK9 for cardiovascular disease management.
PubMed: 38922860
DOI: 10.1111/eci.14273 -
Advanced Science (Weinheim,... Jun 2024Platelets play a key role in physiological hemostasis and pathological thrombosis. Based on the limitations of current antiplatelet drugs, it's important to elucidate...
Platelets play a key role in physiological hemostasis and pathological thrombosis. Based on the limitations of current antiplatelet drugs, it's important to elucidate the mechanisms of regulating platelet activation. In addition to dissolving lipid nutrients, bile acids (BAs) can regulate platelet function. However, the specific mechanisms underlying BAs-mediated effects on platelet activation and thrombotic diseases remain unknown. Therefore, the effects of BAs on platelets and intracellular regulatory mechanisms are explored. It is showed that the inhibitory effect of secondary BAs is more significant than that of primary BAs; lithocholic acid (LCA) shows the highest inhibitory effect. In the process of platelet activation, BAs suppress platelet activation via the spleen tyrosine kinase (SYK), protein kinase B (Akt), and extracellular signal-regulated kinase1/2 (Erk1/2) pathways. Nck adaptor proteins (NCK1) deficiency significantly suppress the activity of platelets and arterial thrombosis. Phosphorylated proteomics reveal that LCA inhibited phosphorylation of syntaxin-11 at S80/81 in platelets. Additional LCA supplementation attenuated atherosclerotic plaque development and reduced the inflammation in mice. In conclusion, BAs play key roles in platelet activation via Syk, Akt, ERK1/2, and syntaxin-11 pathways, which are associated with NCK1. The anti-platelet effects of BAs provide a theoretical basis for the prevention and therapy of thrombotic diseases.
PubMed: 38922767
DOI: 10.1002/advs.202401683 -
Journal of Cardiovascular Pharmacology Apr 2024Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the...
Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.
PubMed: 38922585
DOI: 10.1097/FJC.0000000000001566 -
Biomimetics (Basel, Switzerland) Jun 2024Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel...
Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel of the neointimal layer of the atherosclerotic plaque that can support thrombogenesis upon exposure to human blood. A biomimetic hydrogel of the neointima was produced by culturing THP-1-derived foam cells within 3D collagen hydrogels in the presence or absence of atorvastatin. Prothrombin time and platelet aggregation onset were measured after exposure of the neointimal models to platelet-poor plasma and washed platelet suspensions prepared from blood of healthy, medication-free volunteers. Activity of the extrinsic coagulation pathway was measured using the fluorogenic substrate SN-17. Foam cell formation was observed following preincubation of the neointimal biomimetic hydrogels with oxidized LDL, and this was inhibited by pretreatment with atorvastatin. The neointimal biomimetic hydrogel was able to trigger platelet aggregation and blood coagulation upon exposure to human blood products. Atorvastatin pretreatment of the neointimal biomimetic layer significantly reduced its pro-aggregatory and pro-coagulant properties. In the future, this 3D neointimal biomimetic hydrogel can be incorporated as an additional layer within our current thrombus-on-a-chip model to permit the study of atherosclerosis development and the screening of anti-thrombotic drugs as an alternative to current animal models.
PubMed: 38921252
DOI: 10.3390/biomimetics9060372 -
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