Inflammation in atherosclerosis: a Big Idea that has underperformed so far

Current Opinion in Lipidology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Purpose of review For many years, inflammation has been a major concept in basic research on atherosclerosis and the development potential diagnostic tools treatments. The purpose this is to assess performance with an emphasis recent clinical trials. In addition, contemporary literature may help identify new therapeutic targets, particularly context treatment early, rather than end-stage, arterial disease. Recent findings Newly reported trials cast doubt efficacy colchicine, sole anti-inflammatory agent currently approved for use patients atherosclerotic cardiovascular disease (ASCVD). New analyses also challenge hypothesis that residual ASCVD event risk after optimal management lipids, blood pressure, smoking arises primarily from inflammatory risk. Current practice initiate interventions so late course be better explanation. Lipid-lowering therapy early atherosclerosis, possibly combined novel add-on agents specifically accelerate resolution maladaptive inflammation, more fruitful conventional approach testing immunosuppressive strategies end-stage Also discussed ongoing revolution noninvasive technologies image wall. These are changing screening, diagnosis, including reversable Summary burden proof Big Idea value remains responsibility its advocates. This requires convincing trial data but still seems largely unmet. Unfortunately, focus as source distracted us need screen treat earlier.

Language: Английский

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Editorial: Vascular- and immuno-metabolism as drivers of cardiovascular disease: insights obtained from omics approaches

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 29, 2025

Despite previous achievements in the management of cardiovascular disease (CVD), and fact that mortality rate from CVD has declined over last 50 years, atherosclerosis, chronic condition responsible for occurrence a myocardial infarction (MI) stroke, remains one primary causes global morbidity mortality. Due to rising aging population combination with an increase cardiometabolic risk factors, primarily driven by obesity epidemic, number individuals affected is still rising. Therefore, it utter importance develop new strategies aimed at reducing elucidate molecular mechanisms important players atherosclerosis. Over past became increasingly clear atherosclerosis multifactorial not only lipids but also vascular damage inflammation.[1; 2; 3] Compelling evidence inflammation play crucial role atherosclerotic was provided CANTOS, performed 2017. Here shown monoclonal antibody targeting interleukin-1b, termed Canakinumab, effectively reduced mortality, especially patients characterized residual inflammation. This effect independent lipid-level lowering. [4] In late 2019, hypothesis confirmed COLCOT, using anti-inflammatory agent colchicine recent MI. [5] A follow-up randomized clinical trial 2020 applying involving coronary (LoDoCo), showed significant reduction. [6] These landmark studies set stage identifying drug targets block atherosclerosis-specific inflammatory pathways as highly promising strategy reduce risk. It now undisputed cellular metabolism fueling many pro-atherosclerotic processes plethora cells involved progression, ranging endothelial smooth muscle cells, neutrophils, T B-lymphocytes monocytes. [7; 8; 9] Advancing omics technologies provide unprecedented insights into mechanisms, offering comprehensive unbiased view metabolic immune functions. [10; 11] The articles this Research Topic both vascular-and immuno-metabolism, drivers CVD, which utmost be able offer therapeutic approaches combat progression. One main challenges multi-omics obtain material various techniques same cell population. their research article, Del Barrio Calvo et al. (https://doi.org/10.3389/fcell.2024.1450971) describe phenotyping approach simultaneous extraction lipids, metabolites RNA single populations employed, enabling multiomic profiling very low numbers. Furthermore, they phenotype MyD88-knockout macrophages proof principle demonstrating potency approach. Another original manuscript Ma colleagues (https://doi.org/10.3389/fcvm.2024.1421071) deploys bioinformatic analysis machine learning evaluate shared pathogenic between ankylosing spondylitis. They identified ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 (ST8SIA4), polysialyltransferase located Golgi apparatus key diagnostic marker progression well spondylitis, revealing component common pathological mechanism. Moreover, Rauterberg (https://doi.org/10.3389/fcvm.2024.1463844) investigates impact Proprotein convertase subtilisin/kexin type 9 (PCSK9) on heart function after MI, outcomes due development, showing lack Pcsk9 mice improves survival post-MI. Interestingly, Alirocumab (PCSK9 inhibitor) treatment did replicate these beneficial effects mice, highlighting there seems mechanistic differences differential PCSK9 pharmacological inhibition genetic deficiency. context Peletier (https://doi.org/10.3389/fcell.2024.1494911) summarizes current state-of-the-art 3D models ischemia-reperfusion injury (IRI). elaborate review particularly focusses aspect cell-cell communication potential enhance our understanding IRI. Besides articles, includes several reviews. Indeed, Pi (https://doi.org/10.3389/fimmu.2024.1437821) detailed overview evolution involvement innate adaptive pathology. Particularly, studies, single-cell RNA-sequencing are discussed highlight large degree heterogeneity within different subsets. further supported Annink (https://doi.org/10.3389/fcell.2024.1446758) highlights emphasizing being pursued order identify novel context. specifically 2 lymphoid (ILC2s), have recently emerged major regulators pathogenesis diseases. [12] Kral (https://doi.org/10.3389/fcell.2024.1473616) ILC2s disorders. review, characteristics ILC2s, thereby diversity Dai (https://doi.org/10.3389/fcell.2024.1446964) describes changes macrophages, lymphocytes comorbidities. An such could diseases can metabolism, while vice versa altered severely development.Another player development NOD-like receptor protein 3 (NLRP3) inflammasome, been studied extensively already systematic Miao (https://doi.org/10.3389/fcvm.2024.1407721) valuable regarding NLRP3 inflammasome field decade CVD. Their reveals leading contributors like oxidative stress, pyroptosis, conclusion, aims series covering all aspects how immuno-metabolism modulation used alter contribute improved options future.

Language: Английский

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Low-Dose Docetaxel Is Effective in Reducing Atherogenic Lipids and Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1484 - 1484

Published: Feb. 11, 2025

High-density lipoprotein (HDL) particles form during cellular cholesterol removal, positioning HDL biogenesis as a potential strategy to combat atherosclerosis. We identified desmocollin 1 (DSC1) negative regulator of and discovered that docetaxel (DTX) effectively inhibits DSC1 activity. This study assessed the efficacy DTX in reducing atherosclerosis ApoE−/− mice. After two weeks on high-fat diet, mice were divided into baseline, vehicle-treated, DTX-treated groups. Baseline sacrificed at end weeks, while other groups received vehicle or (1 μg/μL) via subcutaneously implanted osmotic pumps delivering 0.15 μL/h for six with diet continued. The controlled drug delivery system maintained stable blood concentrations (2.7–4.3 nM) over without hematologic toxicity. treatment significantly reduced circulating atherogenic lipids, including triglycerides, non-esterified fatty acids, low-density cholesterol, total increasing cholesterol/total ratio. These improvements associated significant reductions atherosclerotic lesions aortic sinus arch. Notably, these effects occurred altering inflammatory cytokine levels. results demonstrate reduces dyslipidemia-induced Its HDL-biogenic anti-atherosclerotic establish promising candidate developing HDL-directed therapies

Language: Английский

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Targeting Atherosclerosis via NEDD4L Signaling—A Review of the Current Literature

Biology, Journal Year: 2025, Volume and Issue: 14(3), P. 220 - 220

Published: Feb. 20, 2025

Cardiovascular diseases are the primary cause of mortality worldwide. In this scenario, atherosclerotic cardiovascular outcomes dominate since their incidence increases as populations grow and age. Atherosclerosis is a chronic inflammatory disease that affects arteries. Although its pathophysiology heterogeneous, some genes indissociably associated with occurrence, understanding effects on disease’s occurrence could undoubtedly define effective screening treatment strategies. One such gene NEDD4L. The NEDD4L related to ubiquitin ligase enzyme activities. It essential regulate vascular inflammation, atherosclerosis plaque stability, endothelial smooth cell function, lipid metabolism, particularly in controlling cholesterol levels. However, evidence dubious, no review has yet synthesized targeting atherosclerosis. Therefore, our aims fill gap by analyzing literature concerning occurrence. To achieve goal, we performed systematic search reputable databases, including PubMed, Google Scholar, Web Science, Scopus, Embase. inclusion criteria comprised peer-reviewed original studies using vitro animal models due unavailability relevant clinical studies. Systematic reviews, meta-analyses, articles did not focus relationship between those unrelated health condition were excluded. Studies written English language also strategy included from January 2000 2025 final analysis capture recent advancements. Following screening, five included. Most underscored NEDD4L’s role increasing formation, but other indicated stimulating may positively counter formation. future research endeavors must address several limitations, which have been tentatively highlighted throughout manuscript, for more informative based preclinical successfully translate findings into trials.

Language: Английский

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Active Immunization Using TRPM2 Peptide Vaccine Attenuates Atherosclerotic Progression in a Mouse Model of Atherosclerosis

Vaccines, Journal Year: 2025, Volume and Issue: 13(3), P. 241 - 241

Published: Feb. 26, 2025

Background/Objective: Atherosclerosis is one of the leading causes cardiovascular diseases and mortality around world. One exciting strategy for atherosclerosis treatment immunotherapy, especially active immunization. Active immunization relies on delivery antigens in a vaccine platform to introduce humoral cellular immunity, alleviating atherosclerotic progression. Transient receptor potential channel isoform M2 (TRPM2) an ROS-activated Ca2+-permeable ion that can promote via stimulating vascular inflammation. In present study, we developed with TRPM2 E3 domain peptide platform, aiming induce endogenous production anti-TRPM2 blocking antibody mice vivo, consequently inhibiting activity alleviate Methods: ApoE knockout were fed high cholesterol diet develop atherosclerosis. The injected or without vaccines, followed by analysis lesion en face Oil Red O staining whole aorta histologic thin tissue sections from aortic roots. Results: results show pig region-based (P1) could effectively diet-induced mice. We worked out best formulation most effective atheroprotection, namely P1 at dose 67.5 µg per mouse (2.5 mg/kg body weight) aluminum salts as adjuvant. Conclusions: study provides novel target vaccine-based anti-atherosclerotic lays foundation future preclinical/clinical trials using therapeutic option against

Language: Английский

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Harnessing exercise to combat chronic diseases: the role of Drp1-Mediated mitochondrial fission

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 26, 2025

Enhanced Drp1 activity mediates excessive mitochondrial fission, contributing to the onset and progression of various chronic diseases, including neurodegenerative, cardiovascular, metabolic disorders. Studies indicate that exercise mitigates dysfunction by modulating Drp1-related signaling targets, thereby inhibiting reducing fission. This, in turn, enhances function cellular metabolism. This review synthesizes current understanding structure activation mechanisms, analyzes effects interventions on Drp1-mediated fission different disease models improve common conditions. research deepens our insight into specific mechanisms Drp1-induced pathogenesis, offering new theoretical support practical guidance for as a non-pharmacological intervention strategy.

Language: Английский

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Association of nutritional and inflammatory status with all-cause and cardiovascular mortality in adults with sarcopenia: Insights from NHANES

Maturitas, Journal Year: 2025, Volume and Issue: 196, P. 108233 - 108233

Published: March 4, 2025

Language: Английский

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Myricetin alleviates high-fat diet-induced atherosclerosis in ApoE-/- mice by regulating bile acid metabolism involved in gut microbiota remodeling

Food & Function, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Myricetin exerts protective effect against atherosclerosis in high-fat diet-induced ApoE −/− mice by modulating the gut-liver axis.

Language: Английский

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Ultrasound‐Driven Piezoelectric Heterostructures Block Early Atherosclerotic Plaques Progression

Small, Journal Year: 2025, Volume and Issue: unknown

Published: March 16, 2025

Abstract Atherosclerosis (AS), marked by lipid buildup and chronic inflammation in arteries, leads to major cardiovascular events. Macrophages contribute AS engulfing low‐density lipoproteins, forming foam cells, driving that promotes plaque growth instability. The emerging piezocatalytic therapy uses piezoelectric materials generate radicals target inflammation‐related macrophages for treatment, but the conventional suffer from low radical yield, substantially limiting clinical use. In this study, construction of BaTiO 3 /Ta 4 C MXene heterostructured nanosheets (BTOMX NSs) is reported achieving enhanced treatment blocking early atherosclerotic progression. composite BTOMX NSs feature high electron‐hole separation efficiency due their narrowed bandgap surface potential under ultrasound irradiation, enabling more effective generation effects. Especially, these biocompatible accumulate plaques are efficiently internalized macrophages, where they stimulation, ultimately triggering macrophage apoptosis interrupting ApoE −/− mice, remove lesional reduce accumulation, mitigate inflammation, decreasing burden 21.42% 9.04%. Taken together, work provides a paradigm enhancing ‐based performance heterostructure construction, demonstrating an efficient, noninvasive, safe therapeutic approach treating early‐stage AS.

Language: Английский

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Advances in the treatment of atherosclerotic plaque based on nanomaterials

Nanomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: March 20, 2025

Atherosclerosis is the leading cause of cardiovascular disease worldwide, posing not only a significant threat to health but also impairing function multiple organs, with severe cases potentially being life-threatening. Consequently, effective treatment atherosclerosis paramount importance in reducing mortality associated diseases. With advancement nanomedicine and deeper understanding pathological mechanisms underlying atherosclerosis, nanomaterials have emerged as promising platforms for precise diagnosis targeted therapeutic strategies. These materials offer notable advantages, including drug delivery, enhanced bioavailability, improved stability, controlled release. This review provides an overview atherosclerotic plaque development examines nanomaterial-based approaches managing plaques, therapies targeting cholesterol metabolism, anti-inflammatory strategies, macrophage clearance, immunotherapy. Additionally, paper discusses current technical challenges clinical transformation these therapies. Finally, potential future integration nanomaterials, smart artificial intelligence explored.

Language: Английский

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