Therapy Of Atherosclerosis Research Articles

Targeted and Biomimetic Nanoparticles for Atherosclerosis Therapy: A Review of Emerging Strategies

Atherosclerosis, a chronic inflammatory disease, remains a leading cause of cardiovascular mortality worldwide. Despite standard treatments like statins and percutaneous coronary intervention (PCI), significant residual risk and therapeutic limitations underscore the need for innovative strategies. This review summarizes recent advances in nanoparticle-based therapies for atherosclerosis, focusing on key developments from the last five years. We discuss various nanoplatforms designed to selectively target key cellular players in plaque pathogenesis, including macrophages, endothelial cells, and vascular smooth muscle cells (VSMCs), to inhibit inflammation, modulate cellular phenotypes, and stabilize plaques. A significant focus is placed on the emerging field of biomimetic nanoparticles, where therapeutic cores are camouflaged with cell membranes derived from macrophages, platelets, neutrophils, or erythrocytes. This approach leverages the natural biological functions of the source cells to achieve enhanced immune evasion, prolonged circulation, and precise targeting of atherosclerotic lesions. Furthermore, the review covers nanoparticles engineered for specific functional interventions, such as lowering LDL levels and exerting direct anti-inflammatory and anti-oxidative effects. Finally, we address the critical challenges hindering clinical translation, including nanotoxicity, biodistribution, and manufacturing scalability. In conclusion, nanotechnology offers a versatile and powerful platform for atherosclerosis therapy, with targeted and biomimetic strategies holding immense promise to revolutionize future cardiovascular medicine.

A programmable platelet theranostic platform for adaptive multi-stage delivery and synergistic immunotherapy in atherosclerosis

Macrophages, along with the inflammatory and maladaptive immune responses they trigger, play crucial roles in the progression and rupture of atherosclerosis. We develop an adaptable platelet-protein platform tailored for the targeted delivery of both antioxidant nanocatalysts and TRAF6 inhibitor to advance synergistic therapy for atherosclerosis. The platform is constructed by assembling nanocatalyst- and TRAF6 inhibitor-loaded protein clusters with reactive oxygen species-cleavable linkers, then anchoring them onto the platelet surface for guided delivery to atherosclerotic plaques. Upon entering the reactive oxygen species-rich microenvironment, the platform disintegrates into ultra-small protein blocks, facilitating plaque penetration and selective macrophage internalization. The Mn-based nanocatalyst effectively scavenges various reactive oxygen species, while Mn ions concurrently enhance T1-weighted magnetic resonance imaging signals for diagnosis of atherosclerotic plaques. Meanwhile, the TRAF6 inhibitor blocks macrophage activation mediated by T lymphocytes. In a male mouse model of atherosclerosis, the versatile platform integrates cell-mediated natural targeting with adaptable size transformation for enhanced intraplaque penetration and unfavorable macrophage signaling reprogramming, offering opportunities for precise and multifaceted atherosclerosis therapy.

Fabrication of macrophage-membrane coated functionalized ROS-responsive thiolated chitosan-based nanoparticles to attenuate atherosclerosis: Investigation on diabetic hyperlipidaemia-induced mice model.

Fabrication of macrophage-membrane coated functionalized ROS-responsive thiolated chitosan-based nanoparticles to attenuate atherosclerosis: Investigation on diabetic hyperlipidaemia-induced mice model.

Vascular cellular senescence in human atherosclerosis: The critical modulating roles of CDKN2A and CDK4/6 signaling pathways.

Vascular cellular senescence in human atherosclerosis: The critical modulating roles of CDKN2A and CDK4/6 signaling pathways.

Disrupted structural network resilience in atherosclerosis: A large-scale cohort study.

Disrupted structural network resilience in atherosclerosis: A large-scale cohort study.

Biomimetic Ginsenoside Rb1 and Probucol Co-Assembled Nanoparticles for Targeted Atherosclerosis Therapy via Inhibition of Oxidative Stress, Inflammation, and Lipid Deposition.

To overcome the limitations of conventional oral drugs and nanocarrier-dependent delivery systems in atherosclerosis (AS) therapy, our work proposes an "integration of Chinese and Western medicine" approach to develop a new biomimetic traditional Chinese and Western medicine components coassembled nanoparticles (NPs), termed as MMVs/RPNPs, for targeted AS therapy. In this work, we demonstrated that ginsenoside Rb1 can coassemble with probucol without excipients to form stable carrier-free NPs, termed RPNPs. To impart the specific targeting property to atherosclerotic sites, macrophage microvesicles (MMVs) were utilized to coat the RPNPs to obtain the MMVs/RPNPs. Developed MMVs/RPNPs exhibited excellent capabilities in eliminating intracellular ROS, suppressing pro-inflammatory factor secretion, and inhibiting intracellular lipid deposition in vitro. In a mouse model of AS, MMVs/RPNPs efficiently accumulated at atherosclerotic sites following intravenous injection and effectively retarded atherosclerotic plaque formation through synergistic effects of antioxidative stress, anti-inflammation, and inhibition of lipid deposition. Additionally, MMVs/RPNPs did not cause any adverse effects with long-term treatment. Our work presents simple, effective, and safe NPs against AS and underscores the potential of the "integration of Chinese and Western medicine" strategy for treating other cardio-cerebrovascular diseases.

Harnessing extracellular vesicles to tame inflammation: a new strategy for atherosclerosis therapy.

Atherosclerosis (AS) is a chronic inflammatory disease driven by immune dysregulation and vascular inflammation. Extracellular vesicles (EVs) play pivotal roles in intercellular communication, modulating immune responses and inflammatory cascades during AS progression. EVs derived from endothelial cells, macrophages, vascular smooth muscle cells, and platelets transport bioactive molecules (e.g., miRNAs, cytokines) that regulate endothelial dysfunction, macrophage polarization, and plaque instability. Pro-inflammatory EVs exacerbate oxidative stress, foam cell formation, and neutrophil extracellular trap (NET) release, while anti-inflammatory EVs from mesenchymal stem cells or engineered sources attenuate disease by promoting M2 macrophage polarization and suppressing NF-κB signaling. This review highlights the dual roles of EVs in AS immunopathology and their therapeutic potential as biomarkers or nanocarriers for targeted anti-inflammatory interventions. Understanding EV-mediated immune crosstalk may unveil novel strategies for atherosclerosis management.

Plasma Fatty Acid Profiling and Mathematical Estimation of the Omega-3 Index: Toward Diagnostic Tools in Atherosclerosis and Statin Therapy Monitoring.

Background/Objectives: Omega-3 highly unsaturated fatty acids (HUFAs), particularly EPA and DHA, have anti-inflammatory and lipid-modulating properties for treating atherosclerosis. However, the relationship between plasma fatty acid profiles, omega-3 status, and statin efficacy in carotid atherosclerosis remains poorly defined. Objectives: This study evaluates plasma and plaque fatty acid (FA) composition, explores their associations with plaque stability, and examines the relationship of omega-3 levels, lipid biomarkers (VLDL-C, LDL-C, HDL-C, total cholesterol, and triglycerides) with statin and β-blocker treatment. A mathematical model was developed to predict the erythrocyte omega-3 index from plasma. Methods: In this case-control study, plasma and carotid plaques of 52 patients undergoing carotid endarterectomy were analyzed. Plasma was compared with that of 50 healthy controls. FAs were quantified by LC-MS/MS. Plaques were histologically classified as stable or unstable. Results: Atherosclerotic patients showed disturbed FA metabolism, including decreased plasma omega-3 EPA + DHA, SFAs and HUFAs, increased MUFAs, and impaired desaturase and elongase activity. Unstable plaques had higher MUFA and lower HUFA content compared with stable plaques. Significant correlations between plasma EPA + DHA and HDL-C and triglycerides were observed in statin-naïve patients, whereas statins appeared to attenuate these associations. Co-treatment with β-blockers had no significant effect. A validated logit-based model accurately predicted the erythrocyte omega-3 index from plasma (R2 = 0.782). Conclusions: Altered plasma and plaque FA profiles correlate with atherosclerosis's plaque instability and inflammatory lipid profiles. Statins significantly influence these associations, suggesting their complex interaction with lipid metabolism. Plasma measurements of omega-3 fatty acids in combination with predictive modelling may be beneficial for diagnostic and therapeutic monitoring in carotid atherosclerosis.

Age and effect of intensive statin in acute mild ischemic stroke or transient ischemic attack: Subgroup analysis of the INSPIRES trial.

Age and effect of intensive statin in acute mild ischemic stroke or transient ischemic attack: Subgroup analysis of the INSPIRES trial.

Dual-targeted microbubbles for atherosclerosis therapy: Inducing M1 macrophage apoptosis by inhibiting telomerase activity.

The progression of atherosclerosis (AS) is closely associated with M1 macrophages. Although the activation of macrophage telomerase during plaque formation has been documented, targeted modulation strategies remain challenging. In this study, we developed a dual-target microbubble-delivery system (Ab-MMB1532) encapsulating BIBR1532, a telomerase inhibitor, for the targeted therapy of AS. This system exhibited remarkable targeting capabilities towards M1 macrophages, with its targeting advantage notably accentuated under high shear forces. Mechanistically, Ab-MMB1532 inhibited telomerase activity by downregulating telomerase reverse transcriptase (TERT) expression, subsequently inducing caspase-3-mediated apoptosis. Integrated multi-omics profiling revealed that the inhibition of the NF-κB pathway served as the central regulatory hub. In vivo studies further confirmed that Ab-MMB1532 effectively targets and accumulates within AS lesions, promoting M1 macrophage apoptosis through the inhibition of the TERT/NF-κB signaling axis, and significantly reducing plaque burden (25.4% reduction vs. controls, p<0.001). In summary, our findings suggest a novel approach for telomerase-targeted therapy in AS.

Biomimetic membrane-coated nanoparticles for targeted synergistic therapy of homocysteine-induced atherosclerosis: Dual modulation of cholesterol efflux and reactive oxygen species scavenging

Biomimetic membrane-coated nanoparticles for targeted synergistic therapy of homocysteine-induced atherosclerosis: Dual modulation of cholesterol efflux and reactive oxygen species scavenging

High-density lipoprotein-based nanoplatforms for macrophage-targeted diagnosis and therapy of atherosclerosis.

High-density lipoprotein-based nanoplatforms for macrophage-targeted diagnosis and therapy of atherosclerosis.

Combination therapy and drug co-delivery systems for atherosclerosis.

Combination therapy and drug co-delivery systems for atherosclerosis.

Pitavastatin and resveratrol bio-nanocomplexes against hyperhomocysteinemia-induced atherosclerosis via blocking ferroptosis-related lipid deposition.

Pitavastatin and resveratrol bio-nanocomplexes against hyperhomocysteinemia-induced atherosclerosis via blocking ferroptosis-related lipid deposition.

Rapamycin-loaded Poly(lactic-co-glycolic) acid microspheres optimized by a quality by design approach for atherosclerosis therapy: Preparation, characterization, and in vitro evaluation

Rapamycin-loaded Poly(lactic-co-glycolic) acid microspheres optimized by a quality by design approach for atherosclerosis therapy: Preparation, characterization, and in vitro evaluation

Network pharmacology, molecular docking, and molecular dynamics analyses to explore the molecular mechanism of paclitaxel in atherosclerosis therapy

Atherosclerosis is a chronic arterial disease and the leading cause of vascular death. Paclitaxel has long been recognized as an anticancer agent, but recent studies have shown that paclitaxel can also potentially reduce the progression of atherosclerosis. The aim of this study was to explore the molecular mechanism of paclitaxel as an atherosclerosis therapy using in silico study. Pharmacokinetic and pharmacodynamic analyses of paclitaxel were conducted using SwissADME, ProTox v3.0, and SCFbio websites. Cytoscape software was used to construct a network of protein-protein interactions, and the key proteins involved in paclitaxel-related atherosclerosis were identified, including AKT serine/threonine kinase 1 (AKT1), Jun N-terminal kinase (JNK), and Endothelin 1 (ET1). These key proteins were then subjected to molecular docking and molecular dynamic simulation using MOE and Yasara applications. Pharmacokinetic and pharmacodynamic analyses revealed that paclitaxel has good distribution, metabolism, and excretion properties. However, paclitaxel has shortcomings in absorption, toxicity, and water solubility. According to the results of molecular docking, paclitaxel showed consistent results as the most potential inhibitor of AKT1 (-9.59 kcal/mol), ET1 (-9.16 kcal/mol), JNK (-8.72 kcal/mol) when compared to the control ligands. Molecular dynamics simulations also confirmed the interaction stability between paclitaxel with AKT1, ET1, and JNK, with paclitaxel-AKT1 demonstrating the highest conformational stability (Carbon-α Root Mean Square Deviation &lt;3.0 Å). Even though our in-silico results are promising, more experimental studies are required to confirm the efficacy of paclitaxel as an atherosclerosis therapy.

Systemic lupus erythematosus and atherosclerosis: immune pathways and the uncharted territory of gut microbiota and metabolism.

Patients with Systemic Lupus Erythematosus (SLE) are significantly more susceptible to atherosclerosis, which may elevate their mortality risk. The review explores recent understandings of the origins and remedies for atherosclerosis associated with SLE. Our focus is particularly on the consequences of immune system disparities, interruptions in intestinal bacteria, and metabolic complications. The influence of SLE on atherosclerosis extends past usual risk elements, including processes specific to the disease. The list encompasses excessive immune cell activity, production of autoantibodies, inflammatory responses. A variety of therapies for atherosclerosis linked to SLE encompass cholesterol-lowering medications, anti-inflammatory drugs, immune suppressors, antimalarials, interferon treatments, NET inhibitors, and methods aimed at T and B-cells. However, existing research has its shortcomings, necessitating additional clinical trials to ascertain the efficacy and security of these therapies. The direct interactions among SLE, gut microbiota, metabolism, and atherosclerosis is underexplored, presenting innovation opportunities. Research into specific gut microbial strains and metabolites' effects on immune responses and atherosclerosis progression in SLE patients is needed. Such research could uncover novel therapeutic targets and biomarkers, advancing prevention and treatment strategies for SLE cardiovascular complications.

Microenvironments‐Targeted Nanomaterials for Atherosclerosis Therapy

Abstract Atherosclerosis significantly contributes to cardiovascular disease. Traditional treatments for atherosclerosis, such as pharmacological interventions and surgical procedures, have demonstrated limited efficacy and often yield unsatisfactory results. Consequently, safe and effective therapeutic strategies are urgently needed. The atherosclerotic microenvironments, characterized by inflammation driven by foam cells, damaged endothelial cells, recruited leukocytes, lipoproteins, and inflammatory mediators, play a key role in disease progression. By leveraging the biological components and physicochemical properties of these microenvironments, researchers have developed microenvironments‐targeted nanomaterials as a promising approach to treat atherosclerosis. These nanomaterials aim to address and eliminate inflammatory processes. Their functions include repairing endothelial damage, reducing lipoprotein accumulation, inhibiting leukocyte chemotaxis, suppressing foam cell formation, delaying plaque rupture, and preventing thrombosis within the plaque. This review highlights the therapeutic mechanisms and effects of nanomaterials targeting key processes in atherosclerotic microenvironments. Finally, the challenges and prospects of nanomaterial‐based therapies for atherosclerosis are discussed to inspire the development of nanomaterials that modulate atherosclerotic microenvironments, potentially leading to promising clinical applications.

Advances in Anti-inflammatory Therapies for Cardiovascular Disease and Atherosclerosis

This study aims to provide clinical and scientific information about the effects of various anti-inflammatory medicines on patients with cardiovascular disease (CVD). We also discussed the anti-inflammatory strategies and molecular mechanisms being investigated in preclinical or clinical CVD research. Numerous studies on anti-inflammatory medicines for CVD have resulted from greater knowledge of how innate and adaptive immunity influence plaque development and rupture. Some of these are now being evaluated in clinical trials and use lower dosages of existing medications that were initially developed for other inflammatory disorders with a high risk of CVD, such as rheumatoid arthritis and psoriasis. Other research includes retrospective and meta-analyses of clinical trials that examine the risk of CVD among individuals with various inflammatory diseases. We also included natural bioactive compounds, nanodrug and multiomics approaches to treat CVD by utilizing inflammatory pathways. Chronic subclinical inflammation is a major contributor to the development of CVD and has been associated with both the onset and progression of atherosclerosis. Several pro-inflammatory cytokines, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukins-1 and 6 (IL-1 and IL-6), leukotrienes, and adiponectin, have been identified as independent risk factors for coronary heart disease and promoters of arterial development. Researchers are looking for ways to stop the different inflammatory pathways that lead to atherosclerosis. These include multiomics approach, antioxidants, phospholipase A2 inhibitors, leukotriene pathway inhibitors, Phospholipase A2 (PLA2) inhibitors, non-inhibitors anti-inflammatory drugs (like methotrexate), IL-1 inhibitors, and p-selectin inhibitors.

Effect of history of hypertension on efficacy of clopidogrel-aspirin in ischemic stroke.

Patients with different hypertension status could potentially respond differently to the treatment of clopidogrel-aspirin owing to thrombosis, antiplatelet resistance, and platelet reactivity. The aim of the study is to examine the efficacy and safety of clopidogrel-aspirin in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) according to different hypertension status. In the Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, patients were randomized to either clopidogrel-aspirin or aspirin group. The primary outcome was any new ischemic or hemorrhagic stroke within 90 days. Hypertension status was classified into two categories based on medical history: patients with or without hypertension. Among 6100 patients with complete data of hypertension status, 3915 (64.2%) were men. Clopidogrel-aspirin compared with aspirin was associated with reduced incidence of new stroke in patients without hypertension (hazard ratio (HR): 0.62, 95% confidence interval (CI): 0.44-0.86, p = 0.004), but not in patients with hypertension (HR: 0.87, 95% CI: 0.71-1.07, p = 0.18; p = 0.085 for interaction). In this study, patients without hypertension may have more benefit from receiving treatment with clopidogrel-aspirin than those with hypertension. This finding can be used as an enrichment strategy in the future secondary stroke prevention randomized clinical trials of dual antiplatelet therapy. The INSPIRES trial was registered at http://www. gov (unique identifier: NCT03635749).