The main message of this paper is that current treatment of atherosclerosis relies mainly on standard preventive therapies—cholesterol lowering, combination lipid therapy, and blood-pressure control—whereas future treatment may come from more precise targeting of inflammation, endothelial injury, oxidative stress, immune pathways, and plaque biology. The review maps 47 original research topics, from combination therapies to cannabinoid receptor modulation, and 10 recurrent directions in the non-original literature, from lipid reduction to personalized imaging of plaque burden.
Additional notes
Clinical & Methodological Validation
Abstract: The aim of this paper is to systematically synthesize recent evidence concerning the mechanisms of atherosclerosis and the efficacy of various treatment approaches, as extracted from a structured summary of scientific literature. The review utilises 1015 original studies with 2628810 total participants (topic deduplicated ΣN). This scoping review maps a broad and rapidly expanding treatment landscape for atherosclerosis, with the strongest and most directly actionable human evidence clustering around established lipid-lowering and blood-pressure–lowering strategies, including combination lipid therapy and antihypertensive treatment effects on vascular outcomes. Across the wider evidence map—dominated by preclinical studies—therapeutic signals repeatedly converged on inflammation control, endothelial protection, immune modulation, oxidative stress reduction, and targeted delivery approaches (including nanomedicine and device/energy-based modalities) as routes to reduce plaque burden and improve plaque stability. At the same time, interpretation is limited by the imbalance toward non-human mechanistic studies and the lack of formal critical appraisal, which together temper confidence in near-term clinical translation. Practically, the synthesis supports optimizing implementation of proven preventive therapies and risk identification (e.g., improving statin initiation/intensification through screening workflows) while using emerging mechanistic targets to prioritize translational pipelines. Future research should focus on well-designed human trials that test the most consistently supported anti-inflammatory and targeted-delivery strategies and clarify which patient subgroups benefit most.
Final search date and database lock: 2026-03-13 21:18:31 CET
Plan: Pro (expanded craft tokens; source: PubMed)
Source: PubMed
Total Abstracts/Papers: 153800
Downloaded Abstracts/Papers: 10000
Included original and non-original Abstracts/Papers (all): 1810
Included original Abstracts/Papers (OSMA vote counting by direction of effect): 1015
Reference Index (links used in paper): 270
Total participants (topic deduplicated ΣN): 2628810
Get access to the full paper
Unlock the full evidence map
The full evidence review, including the Introduction, Methods, Results, Discussion, Conclusion, figures, and complete reference index, opens after purchase or sign-in.
The Evidence Object JSON is a separate machine-readable evidence product: a concentrated synthesis of results, topic-level evidence, and discussion across original and non-original studies. It can be directly input into your LLM, agent, or RAG workflow.
[44] When a Friend Becomes Your Enemy: Natural Killer Cells in Atherosclerosis and Atherosclerosis-Associated Risk Factors. — https://doi.org/10.3389/fimmu.2021.798155
[50] Therapies leading to coronary atherosclerosis plaque regression: a scientific statement of the European Association of Preventive Cardiology, the European Association of Cardiovascular Imaging of the ESC, the ESC Working Group on Atherosclerosis and Vascular Biology, and the ESC Working Group on Cardiovascular Pharmacotherapy Part 2-drugs' specific effect on atherosclerosis. — https://doi.org/10.1093/eurjpc/zwaf654
[51] Recent Advances in Anti-Atherosclerosis and Potential Therapeutic Targets for Nanomaterial-Derived Drug Formulations. — https://doi.org/10.1002/advs.202302918
[56] Pathophysiology of atherosclerosis: Association of risk factors and treatment strategies using plant-based bioactive compounds. — https://doi.org/10.1111/jfbc.13449
[91] A narrative review of plant and herbal medicines for delaying diabetic atherosclerosis: an update and future perspectives. — https://doi.org/10.31083/j.rcm2204142
[92] Fisetin Suppresses Atherosclerosis by Inhibiting Ferroptosis-Related Oxidative Stress in Apolipoprotein E Knockout Mice. — https://doi.org/10.1159/000538535
[108] Reactive oxygen species scavenging and inflammation mitigation enabled by biomimetic prussian blue analogues boycott atherosclerosis. — https://doi.org/10.1186/s12951-021-00897-2
[115] Promising Directions in Atherosclerosis Treatment Based on Epigenetic Regulation Using MicroRNAs and Long Noncoding RNAs. — https://doi.org/10.3390/biom9060226
[161] Calycosin ameliorates atherosclerosis by enhancing autophagy via regulating the interaction between KLF2 and MLKL in apolipoprotein E gene-deleted mice. — https://doi.org/10.1111/bph.15720
[239] The Effect of Low-Dose Proteasome Inhibition on Pre-Existing Atherosclerosis in LDL Receptor-Deficient Mice. — https://doi.org/10.3390/ijms18040781
[243] Living Macrophage-Delivered Tetrapod PdH Nanoenzyme for Targeted Atherosclerosis Management by ROS Scavenging, Hydrogen Anti-inflammation, and Autophagy Activation. — https://doi.org/10.1021/acsnano.2c03422
[293] Lipidomics-based investigation of its impact on the pathogenesis of coronary atherosclerosis: a Mendelian randomization study. — https://doi.org/10.1186/s41065-025-00367-x
[294] Pharmacological inhibition of EZH2 by GSK126 decreases atherosclerosis by modulating foam cell formation and monocyte adhesion in apolipoprotein E-deficient mice. — https://doi.org/10.3892/etm.2021.10273
[297] Reprogramming Lesional Macrophage Homeostasis via Interferon Regulatory Factor 5 Targeted siRNA Nanoimmunotherapy for Atherosclerosis. — https://doi.org/10.1021/acsnano.5c18044
[305] Autophagy inhibition and ferroptosis activation during atherosclerosis: Hypoxia-inducible factor 1α inhibitor PX-478 alleviates atherosclerosis by inducing autophagy and suppressing ferroptosis in macrophages. — https://doi.org/10.1016/j.biopha.2023.114333
[311] CircMAPK1 promotes the proliferation and migration of vascular smooth muscle cells through miR-22-3p/ methyl-CpG binding protein 2 axis. — https://doi.org/10.1016/j.numecd.2021.04.005
[313] A novel MyD88 inhibitor LM9 prevents atherosclerosis by regulating inflammatory responses and oxidative stress in macrophages. — https://doi.org/10.1016/j.taap.2019.03.012
[314] The effect of nonsurgical periodontal treatment on serum and gingival crevicular fluid markers in patients with atherosclerosis. — https://doi.org/10.4103/1119-3077.181369
[375] Telomere stabilization by metformin mitigates the progression of atherosclerosis via the AMPK-dependent p-PGC-1α pathway. — https://doi.org/10.1038/s12276-024-01297-w
[381] Oridonin attenuates the progression of atherosclerosis by inhibiting NLRP3 and activating Nrf2 in apolipoprotein E-deficient mice. — https://doi.org/10.1007/s10787-023-01161-9
[407] Ligilactobacillus Murinus and Lactobacillus Johnsonii Suppress Macrophage Pyroptosis in Atherosclerosis through Butyrate-GPR109A-GSDMD Axis. — https://doi.org/10.1002/advs.202501707
[456] Paclitaxel Attenuates Atherosclerosis by Suppressing Macrophage Ferroptosis and Improving Lipid Metabolism via the Sirt1/Nrf2/GPX4 Pathway. — https://doi.org/10.1096/fj.202501047rr
[488] Inhibition of CDK9 attenuates atherosclerosis by inhibiting inflammation and phenotypic switching of vascular smooth muscle cells. — https://doi.org/10.18632/aging.202998
[501] Prevalence and risk factors for subclinical atherosclerosis amongst adults living with HIV in University of Abuja Teaching Hospital, Gwagwalada. — https://doi.org/10.3389/frph.2023.1092211
[566] Inflammatory endothelium-targeted and cathepsin responsive nanoparticles are effective against atherosclerosis. — https://doi.org/10.7150/thno.70896
[568] Biomimetic Nanotherapies: Red Blood Cell Based Core-Shell Structured Nanocomplexes for Atherosclerosis Management. — https://doi.org/10.1002/advs.201900172
[581] Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development. — https://doi.org/10.1111/boc.201500104
[589] MicroRNA-302c-3p inhibits endothelial cell pyroptosis via directly targeting NOD-, LRR- and pyrin domain-containing protein 3 in atherosclerosis. — https://doi.org/10.1111/jcmm.16500
[594] Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens. — https://doi.org/10.1210/jcem.86.1.7151
[602] Monotropein resists atherosclerosis by reducing inflammation, oxidative stress, and abnormal proliferation and migration of vascular smooth muscle cells. — https://doi.org/10.4196/kjpp.24.352
[603] Reduction of Reactive Oxygen Species Accumulation Using Gadolinium-Doped Ceria for the Alleviation of Atherosclerosis. — https://doi.org/10.1021/acsami.2c20492
[615] Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation. — https://doi.org/10.1016/j.phymed.2021.153812
[618] Exploring the Molecular Functions and Immune Relevance of Macrophage-Associated Genes in Atherosclerosis. — https://doi.org/10.1155/humu/9034896
[707] Danhong Injection Attenuates High-Fat-Induced Atherosclerosis and Macrophage Lipid Accumulation by Regulating the PI3K/AKT Insulin Pathway. — https://doi.org/10.1097/fjc.0000000000000691
[709] Morbidity, mortality, and antihypertensive treatment effects by extent of atherosclerosis in older adults with isolated systolic hypertension. — https://doi.org/10.1161/01.str.26.8.1319
[728] Direct Oral Anticoagulant Treatment for Atherosclerosis-Induced Aortic Mural Thrombus in an Elderly Male With Aspirin Resistance. — https://doi.org/10.7759/cureus.62691
[741] Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complex. — https://doi.org/10.1161/circresaha.108.191361
[763] A metal-organic framework-based co-delivery system for atherosclerosis therapy macrophage regulation. — https://doi.org/10.1039/d5tb01423a
[771] Cellular senescence promotes endothelial activation through epigenetic alteration, and consequently accelerates atherosclerosis. — https://doi.org/10.1038/s41598-021-94097-5
[786] Application of therapeutical nanoparticles with neutrophil membrane camouflaging for inflammatory plaques targeting against atherosclerosis. — https://doi.org/10.1016/j.mtbio.2024.101397
[808] Glucose lowering by SGLT2-inhibitor empagliflozin accelerates atherosclerosis regression in hyperglycemic STZ-diabetic mice. — https://doi.org/10.1038/s41598-019-54224-9
[813] Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR mouse model of atherosclerosis. — https://doi.org/10.1042/cs20171066
[829] Individual with subclinical atherosclerosis have impaired proliferation of blood outgrowth endothelial cells, which can be restored by statin therapy. — https://doi.org/10.1371/journal.pone.0099890
[842] Upregulation of microRNA-206 induces apoptosis of vascular smooth muscle cells and decreases risk of atherosclerosis through modulating FOXP1. — https://doi.org/10.3892/etm.2017.5071
[844] The effect of mycophenolate mofetil on disease development in the gld.apoE (-/-) mouse model of accelerated atherosclerosis and systemic lupus erythematosus. — https://doi.org/10.1371/journal.pone.0061042
[846] Genetic and pharmacological targeting of phosphoinositide 3-kinase-gamma reduces atherosclerosis and favors plaque stability by modulating inflammatory processes. — https://doi.org/10.1161/circulationaha.107.720466
[856] Hydrogen sulfide attenuates atherosclerosis induced by low shear stress by sulfhydrylating endothelium NFIL3 to restrain MEST mediated endothelial mesenchymal transformation. — https://doi.org/10.1016/j.niox.2023.11.005
[860] microRNA-19b-3p-containing extracellular vesicles derived from macrophages promote the development of atherosclerosis by targeting JAZF1. — https://doi.org/10.1111/jcmm.16938
[883] Six-Gene Signature Associated with Immune Cells in the Progression of Atherosclerosis Discovered by Comprehensive Bioinformatics Analyses. — https://doi.org/10.1155/2020/1230513
[886] Knockdown of lnc-KCNC3-3:1 Alleviates the Development of Atherosclerosis Downregulation of JAK1/STAT3 Signaling Pathway. — https://doi.org/10.3389/fcvm.2021.701058
[887] A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation. — https://doi.org/10.1155/2019/8709583
[891] Camellia oil ( Abel.) treatment improves high-fat diet-induced atherosclerosis in apolipoprotein E (ApoE) mice. — https://doi.org/10.12938/bmfh.2022-005
[892] The sodium-glucose co-transporter 2 inhibitor tofogliflozin suppresses atherosclerosis through glucose lowering in ApoE-deficient mice with streptozotocin-induced diabetes. — https://doi.org/10.1002/prp2.971
[979] Activation of NLRP3 inflammasomes contributes to hyperhomocysteinemia-aggravated inflammation and atherosclerosis in apoE-deficient mice. — https://doi.org/10.1038/labinvest.2017.30
[984] Experimental study on alleviating atherosclerosis through intervention of mitochondrial calcium transport and calcium-induced membrane permeability transition. — https://doi.org/10.1136/jim-2020-001765
[998] Addition of Estradiol to Cross-Sex Testosterone Therapy Reduces Atherosclerosis Plaque Formation in Female ApoE-/- Mice. — https://doi.org/10.1210/en.2017-00884
[999] CD11b+Gr-1+ myeloid-derived suppressor cells reduce atherosclerotic lesion development in LDLr deficient mice. — https://doi.org/10.1093/cvr/cvw114
[1016] The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE Mice. — https://doi.org/10.1155/2016/6305735
[1017] Transplantation of Autologous Bone Marrow Mononuclear Cells Regulates Inflammation in a Rabbit Model of Carotid Artery Atherosclerosis. — https://doi.org/10.1159/000449201
[1019] Rosuvastatin effect on intima media thickness in adult vs elderly patients. — https://doi.org/10.2741/e577
[1116] N-acetylcysteine reduces the severity of atherosclerosis in apolipoprotein E-deficient mice by reducing superoxide production. — https://doi.org/10.1253/circj.cj-08-1148
[1132] Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression. — https://doi.org/10.1093/cvr/cvv111
[1134] Aggravation of atherosclerosis by hypertension in a subhuman primate model with coarctation of the aorta. — https://doi.org/10.1161/01.res.38.6.63
[1135] Single-cell and spatial transcriptomics map senescent vascular cells in arterial remodeling during atherosclerosis in mice. — https://doi.org/10.1038/s43587-025-00889-z
[1202] Hypercholesterolemia treatment patterns and low-density lipoprotein cholesterol monitoring in patients with a diagnosis of atherosclerosis in clinical practice. — https://doi.org/10.1016/j.amjmed.2008.10.017
[1211] Differential Phagocytosis-Based Photothermal Ablation of Inflammatory Macrophages in Atherosclerotic Disease. — https://doi.org/10.1021/acsami.9b12258
[1240] Ramipril administration to atherosclerotic mice reduces oxidized low-density lipoprotein uptake by their macrophages and blocks the progression of atherosclerosis. — https://doi.org/10.1016/s0021-9150(01)00621-9
[1242] Network pharmacology and experimental analysis to reveal the mechanism of Dan-Shen-Yin against endothelial to mesenchymal transition in atherosclerosis. — https://doi.org/10.3389/fphar.2022.946193
[1244] Myeloid protein tyrosine phosphatase 1B (PTP1B) deficiency protects against atherosclerotic plaque formation in the ApoE mouse model of atherosclerosis with alterations in IL10/AMPKα pathway. — https://doi.org/10.1016/j.molmet.2017.06.003
[1248] Proposed synergistic effect of calcium channel blockers with lipid-lowering therapy in retarding progression of coronary atherosclerosis. — https://doi.org/10.1023/a:1007733311487
[1259] Identification of Potential Therapeutic Targets for Coronary Atherosclerosis from an Inflammatory Perspective Through Integrated Proteomics and Single-Cell Omics. — https://doi.org/10.3390/ijms26136201
[1264] Cysteamine Decreases Low-Density Lipoprotein Oxidation, Causes Regression of Atherosclerosis, and Improves Liver and Muscle Function in Low-Density Lipoprotein Receptor-Deficient Mice. — https://doi.org/10.1161/jaha.120.017524
[1278] Blockade of endothelial adenosine receptor 2 A suppresses atherosclerosis in vivo through inhibiting CREB-ALK5-mediated endothelial to mesenchymal transition. — https://doi.org/10.1016/j.phrs.2024.107156
[1279] Extracellular vesicles derived from PM2.5-exposed alveolar epithelial cells mediate endothelial adhesion and atherosclerosis in ApoE mice. — https://doi.org/10.1096/fj.202100927rr
[1288] Suppression of vascular cell adhesion molecule-1 expression by crocetin contributes to attenuation of atherosclerosis in hypercholesterolemic rabbits. — https://doi.org/10.1016/j.bcp.2005.07.034
[1291] Macrophage Membrane Spontaneously Encapsulated Cyclodextrin-Based Nanomedicines for Improving Lipid Metabolism and Inflammation in Atherosclerosis. — https://doi.org/10.1021/acsami.4c11370
[1292] Preclinical Reversal of Atherosclerosis by FDA-Approved Compound that Transforms Cholesterol into an Anti-Inflammatory "Prodrug". — https://doi.org/10.1089/rej.2016.1849
[1304] Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis. — https://doi.org/10.1161/01.atv.17.1.217
[1321] Immunoproteasomal Inhibition With ONX-0914 Attenuates Atherosclerosis and Reduces White Adipose Tissue Mass and Metabolic Syndrome in Mice. — https://doi.org/10.1161/atvbaha.123.319701
[1324] B- and T-lymphocyte attenuator stimulation protects against atherosclerosis by regulating follicular B cells. — https://doi.org/10.1093/cvr/cvz129
[1338] Screening of the Abdominal Aorta During Routine Echocardiographic Examination Is Cost-effective and Leads to Increase in Statin Utilization by Detecting Subclinical Atherosclerosis. — https://doi.org/10.1097/hpc.0000000000000237
[1343] Genetic and pharmacological manipulation of urotensin II ameliorate the metabolic and atherosclerosis sequalae in mice. — https://doi.org/10.1161/atvbaha.112.252973
[1344] The deleterious influence of tenofovir-based therapies on the progression of atherosclerosis in HIV-infected patients. — https://doi.org/10.1155/2012/372305
[1351] Melatonin attenuates smoking-induced atherosclerosis by activating the Nrf2 pathway via NLRP3 inflammasomes in endothelial cells. — https://doi.org/10.18632/aging.202829
[1368] NRP2 promotes atherosclerosis by upregulating PARP1 expression and enhancing low shear stress-induced endothelial cell apoptosis. — https://doi.org/10.1096/fj.202101250rr
[1375] Effect of combined treatment with bisphosphonate and vitamin D on atherosclerosis in patients with systemic lupus erythematosus: a propensity score-based analysis. — https://doi.org/10.1186/s13075-018-1589-9
[1427] An Ultrasound-Responsive Theranostic Cyclodextrin-Loaded Nanoparticle for Multimodal Imaging and Therapy for Atherosclerosis. — https://doi.org/10.1002/smll.202200967
[1444] Treatment of cholesterol-fed rabbits with dietary vitamins E and C inhibits lipoprotein oxidation but not development of atherosclerosis. — https://doi.org/10.1093/jn/124.11.2123
[1478] Effects of atorvastatin in combination with ezetimibe on carotid atherosclerosis in elderly patients with hypercholesterolemia. — https://doi.org/10.4238/2014.april.3.10
[1491] Berberine Attenuates Cholesterol Accumulation in Macrophage Foam Cells by Suppressing AP-1 Activity and Activation of the Nrf2/HO-1 Pathway. — https://doi.org/10.1097/fjc.0000000000000769
[1500] Expanded granulocyte/monocyte compartment in myeloid-specific triple FoxO knockout increases oxidative stress and accelerates atherosclerosis in mice. — https://doi.org/10.1161/circresaha.112.300749
[1509] Transcarotid artery revascularization outperforms transfemoral carotid artery stenting regardless of aortic arch type or degree of atherosclerosis. — https://doi.org/10.1016/j.jvs.2024.07.101
[1542] Exploring the Molecular Mechanism of Schisandrin C for the Treatment of Atherosclerosis via the PI3K/AKT/mTOR Autophagy Pathway. — https://doi.org/10.1021/acsomega.4c03738
[1587] Characteristics of carotid atherosclerosis in elderly patients with type 2 diabetes at different disease course, and the intervention by statins in very elderly patients. — https://doi.org/10.1111/jdi.12710
[1591] Atherosclerosis in a managed care plan: hypercholesterolemia treatment patterns and low-density lipoprotein cholesterol monitoring. — https://doi.org/10.1016/j.jacl.2009.10.004
[1594] Selective resolution of plaques and treatment of atherosclerosis by biophysical alteration of "cellular" and "intracellular" properties. — https://doi.org/10.1016/0306-9877(81)90118-3
[1601] Progression of disease preceding lower extremity amputation in Denmark: a longitudinal registry study of diagnoses, use of medication and healthcare services 14 years prior to amputation. — https://doi.org/10.1136/bmjopen-2017-016030
[1618] Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). — https://doi.org/10.1161/01.cir.103.7.919
[1626] Transient Receptor Potential Ankyrin 1 Channel Involved in Atherosclerosis and Macrophage-Foam Cell Formation. — https://doi.org/10.7150/ijbs.15229
[1690] Treatment of atherosclerosis through transplantation of endothelial progenitor cells overexpressing dimethylarginine dimethylaminohydrolase (DDAH) in rabbits. — https://doi.org/10.1016/j.ijcard.2021.01.036
[1728] Mechanisms of wogonoside in the treatment of atherosclerosis based on network pharmacology, molecular docking, and experimental validation. — https://doi.org/10.1186/s12906-025-04760-x
[1730] Effects of the Lipid Metabolites and the Gut Microbiota in ApoE Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis. — https://doi.org/10.3389/fmolb.2022.786492
[1770] Left ventricular assist device implantation combined with hemiarch replacement for severe aortic atherosclerosis. — https://doi.org/10.21037/jtd-23-255
[1773] Effect of Repaglinide on Blood Glucose, Endothelial Function, Lipid Metabolism, and Inflammatory Reaction in a Rat Model of Atherosclerosis. — https://doi.org/10.1177/1559325820918762
[1806] A ROS and shear stress dual-sensitive bionic system with cross-linked dendrimers for atherosclerosis therapy. — https://doi.org/10.1039/d1nr05355h
[1808] Inhibition of NFAT suppresses foam cell formation and the development of diet-induced atherosclerosis. — https://doi.org/10.1096/fj.202100947r
[1810] Lactic acid bacteria prevent both periodontitis and atherosclerosis exacerbated by periodontitis in spontaneously hyperlipidemic mice. — https://doi.org/10.1111/jre.12874
