Explore the vast range of titles available.

[This corrects the article DOI: 10.1371/journal.pone.0303869.].

Background The aberrantly increased proliferation and migration of vascular smooth muscle cells (VSMCs) was critically associated with atherosclerosis (AS) progression. MiR-197-3p has been confirmed to regulate various biological processes, such as tumorigenesis; however, whether miR-197-3p is involved with the pathological development of AS remains largely unknown. Methods The serum levels of miR-197-3p in AS patients and healthy donors were determined by polymerase chain reaction (PCR) assay. The transfection efficacies of miR-197-3p mimic or inhibitor in VSMCs were evaluated by PCR assay. The effects of miR-197-3p on VSMC proliferation and migration were determined by EdU cell proliferation and Traswell migration assays. Western blotting was conducted to evaluate the effect of miR-197-3p on WDR5 expression in VSMCs. Results In the present study, we found that the expression of miR-197-3p was decreased in the serum of AS patients compared to healthy donors. Overexpression of miR-197-3p inhibited the proliferation and migration of VSMCs, while silencing miR-197-3p showed opposite effects. Mechanistical study revealed that WD Repeat Domain 5 (WDR5) was a target of miR-197-3p. Moreover, miR-197-3p was downregulated in VSMCs upon IL6 treatment and inhibited IL6-induced proliferation and migration in VSMCs. Conclusions These findings indicate that miR-197-3p could serve as a promising diagnostic marker for AS and that targeting IL6/miR-197-3p/WDR5 axis might be a potential approach to treat AS.

IntroductionThe diagnosis of large vessel occlusion (LVO) with underlying intracranial atherosclerotic disease (ICAD) before endovascular treatment (EVT) continues to be a challenge.AimWe aimed to analyze baseline clinical-radiological variables associated with ICAD-LVO before EVT.MethodsRetrospective study of consecutive patients with stroke treated with EVT from January-2020 to April-2022. We included anterior intracranial LVO (ICA, MCA-M1,2) and analyzed baseline clinico-radiological variables associated with ICAD-LVO. We evaluated the diagnostic value of a multivariate regression model and a weighted scale to diagnose ICAD-LVO before EVT. ICAD-LVO was defined as the presence of angiographic residual stenosis or a trend to re-occlusion during EVT.ResultsOf 338 patients included, 28 patients (8.3%) presented with ICAD-LVO. After adjusting for confounders, absence of atrial fibrillation (OR 10.19, 95%CI 1.12–86.6; p=0.033), lower hypoperfusion intensity ratio (HIR [Tmax>10s/Tmax>6s ratio], OR 0.02, 95%CI 0.00–0.41; p=0.013), presence of symptomatic intracranial artery calcification (IAC, OR 6.94, 95%CI 1.69–28.45, p=0.007), presence of a more proximal occlusion (ICA, MCA-M1: OR 3.16, 95%CI 1.03–9.67; p=0.044) and smoking (OR 3.26, 95%CI 1.21–8.75; p=0.019) were associated with ICAD-LVO. A weighted scale based on the covariates such as HIR (3points), absence of AF (2p), IAC (1p), occlusion location (1p) and smoking (1p) predicted ICAD-LVO with good accuracy (AUC=0.88, 95%CI 0.83–0.94; p<0.001).ConclusionA combination of clinical and radiological variables available before EVT can accurately predict the presence of an ICAD-LVO. The ICAD-Scale could be useful to perform a rapid assessment of underlying etiology and suggest specific pathophysiology-based measures (adjunctive pharmacological treatment, angioplasty and/or intracranial stenting).Disclosure of InterestDr Molina reported receiving personal fees from AstraZeneca for consultant services outside the submitted work. Dr Tomasello reported receiving personal fees from Anaconda Biomed, Balt, Medtronic, Perflow, and Stryker outside the submitted work. Dr Ribo reported receiving personal fees from Anaconda Biomed, AptaTargets, Cerenovus, Medtronic, Methinks, Philips, Sanofi, Stryker, Balt, and Rapid AI outside the submitted work; he has a modest ownership of NoraHealth. The other authors report no conflicts. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Emerging evidence has spurred a considerable evolution of concepts relating to atherosclerosis, and has called into question many previous notions. Here I review this evidence, and discuss its implications for understanding of atherosclerosis. The risk of developing atherosclerosis is no longer concentrated in Western countries, and it is instead involved in the majority of deaths worldwide. Atherosclerosis now affects younger people, and more women and individuals from a diverse range of ethnic backgrounds, than was formerly the case. The risk factor profile has shifted as levels of low-density lipoprotein (LDL) cholesterol, blood pressure and smoking have decreased. Recent research has challenged the protective effects of high-density lipoprotein, and now focuses on triglyceride-rich lipoproteins in addition to low-density lipoprotein as causal in atherosclerosis. Non-traditional drivers of atherosclerosis—such as disturbed sleep, physical inactivity, the microbiome, air pollution and environmental stress—have also gained attention. Inflammatory pathways and leukocytes link traditional and emerging risk factors alike to the altered behaviour of arterial wall cells. Probing the pathogenesis of atherosclerosis has highlighted the role of the bone marrow: somatic mutations in stem cells can cause clonal haematopoiesis, which represents a previously unrecognized but common and potent age-related contributor to the risk of developing cardiovascular disease. Characterizations of the mechanisms that underpin thrombotic complications of atherosclerosis have evolved beyond the ‘vulnerable plaque’ concept. These advances in our understanding of the biology of atherosclerosis have opened avenues to therapeutic interventions that promise to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases. This Review discusses recent research that has transformed our understanding of the biology of atherosclerosis, and examines its implications for the treatment of atherosclerotic cardiovascular disease.

Immunologic research into pathogenic mechanisms operating in autoimmune-mediated atherosclerosis initially focused on adaptive immunity. Current interest is directed to more basic inflammatory mechanisms. Chronic inflammation (innate immunity-associated) may trigger initial events that can lead to atherosclerotic cardiovascular disease. This chronic inflammation may start early in life and be perpetuated by classic atherosclerosis risk factors. Lipid peroxidation of low-density lipoprotein seems to be a key event in the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein triggers inflammatory and immunogenic events that promote endothelial dysfunction and the synthesis and secretion of pro-inflammatory cytokines, leading to an autoimmune response capable of accelerating the intracellular accumulation of lipids within atherosclerotic plaques. Oxidized low-density lipoprotein binds β2-glycoprotein I to form circulating complexes found in both autoimmune and non-autoimmune atherosclerosis. It is likely that β2-glycoprotein I and/or these complexes contribute to early atherogenesis by stimulating pro-inflammatory innate immunity through endogenous sensors and inflammasome/interleukin-1 pathways. We discuss the chronic inflammatory (innate) and autoimmune (adaptive) responses operating in atherosclerosis to discern the role of autoimmunity in atherosclerotic cardiovascular disease.

Atherosclerosis is a chronic inflammatory disease that affects medium- and large-sized arteries and remains a leading cause of global morbidity and mortality [...].Atherosclerosis is a chronic inflammatory disease that affects medium- and large-sized arteries and remains a leading cause of global morbidity and mortality [...].

Hyperlipidaemia is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Risk of cardiovascular events depends on cumulative lifetime exposure to low-density lipoprotein cholesterol (LDL-C) and, independently, on the time course of exposure to LDL-C, with early exposure being associated with a higher risk 1 . Furthermore, LDL-C fluctuations are associated with ASCVD outcomes 2 – 4 . However, the precise mechanisms behind this increased ASCVD risk are not understood. Here we find that early intermittent feeding of mice on a high-cholesterol Western-type diet (WD) accelerates atherosclerosis compared with late continuous exposure to the WD, despite similar cumulative circulating LDL-C levels. We find that early intermittent hyperlipidaemia alters the number and homeostatic phenotype of resident-like arterial macrophages. Macrophage genes with altered expression are enriched for genes linked to human ASCVD in genome-wide association studies. We show that LYVE1 + resident macrophages are atheroprotective, and identify biological pathways related to actin filament organization, of which alteration accelerates atherosclerosis. Using the Young Finns Study, we show that exposure to cholesterol early in life is significantly associated with the incidence and size of carotid atherosclerotic plaques in mid-adulthood. In summary, our results identify early intermittent exposure to cholesterol as a strong determinant of accelerated atherosclerosis, highlighting the importance of optimal control of hyperlipidaemia early in life, and providing insights into the underlying biological mechanisms. This knowledge will be essential to designing effective therapeutic strategies to combat ASCVD. Early intermittent feeding of mice with a high-cholesterol Western-type diet accelerates atherosclerosis compared with late continuous exposure to the Western-type diet, despite similar cumulative circulating LDL-C levels.

Atherosclerosis is a chronic inflammatory disease; unstable atherosclerotic plaque rupture, vascular stenosis, or occlusion caused by platelet aggregation and thrombosis lead to acute cardiovascular disease. Atherosclerosis-related inflammation is mediated by proinflammatory cytokines, inflammatory signaling pathways, bioactive lipids, and adhesion molecules. This review discusses the effects of inflammation and the systemic inflammatory signaling pathway on atherosclerosis, the role of related signaling pathways in inflammation, the formation of atherosclerosis plaques, and the prospects of treating atherosclerosis by inhibiting inflammation.

(1) Background: Monocytes and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome orchestrate lipid-driven amplification of vascular inflammation promoting the disruption of the fibrous cap. The components of the NLRP3 inflammasome are expressed in macrophages and foam cells within human carotid atherosclerotic plaques and VSMCs in hypertension. Whether monocytes and NLRP3 inflammasome activation are direct triggers of VSMC phenotypic switch and plaque disruption need to be investigated. (2) Methods: The direct effect of oxLDL-activated monocytes in VSMCs co-cultured system was demonstrated via flow cytometry, qPCR, ELISA, caspase 1, and pyroptosis assay. Aortic roots of VSMCs lineage tracing mice fed normal or high cholesterol diet and human atherosclerotic plaques were used for immunofluorescence quantification of NLRP3 inflammasome activation/VSMCs phenotypic switch. (3) Results: OxLDL-activated monocytes reduced α-SMA, SM22α, Oct-4, and upregulation of KLF-4 and macrophage markers MAC2, F4/80 and CD68 expression as well as caspase 1 activation, IL-1β secretion, and pyroptosis in VSMCs. Increased caspase 1 and IL-1β in phenotypically modified VSMCs was detected in the aortic roots of VSMCs lineage tracing mice fed high cholesterol diet and in human atherosclerotic plaques from carotid artery disease patients who experienced a stroke. (4) Conclusions: Taken together, these results provide evidence that monocyte promote VSMC phenotypic switch through VSMC NLRP3 inflammasome activation with a likely detrimental role in atherosclerotic plaque stability in human atherosclerosis.