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Open research questions in Atherosclerosis and Cardiovascular Diseases

321 gap statements mined from Atherosclerosis and Cardiovascular Diseases papers in our 7.9M-paper local library, which holds 1,414 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The paper highlights the challenge of establishing a therapeutic window for plaque-directed rapalog modulation, given the lack of cell-resolved relationships and the potential for nonlinear biological responses.

    Context-dependent mTOR pharmacology in atherosclerotic plaque stability and exposure-guided modulation · 2026 · DOI

  • It highlights the need for more research on the therapeutic implications of inflammaging and the development of effective strategies for managing acute coronary syndrome in this population.

    Inflammaging and Acute Coronary Syndrome in Elderly Patients: Pathophysiological Mechanisms, Therapeutic Implications and Future Perspectives · 2026 · DOI

  • Need for clinically applicable biomarkers to guide patient selection and treatment.

    Atherosclerosis: From Pathogenesis to Therapeutic Interventions · 2026 · DOI

  • The development of atherosclerosis is a complex process involving multiple factors, including LOX-1. There is a need to understand the molecular mechanisms underlying LOX-1 activation and its role in cardiovascular disease.

    LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review · 2024 · DOI

  • Despite significant advances in understanding the pathophysiology, effective anti-atherosclerotic therapies targeting oxidative stress remain elusive.

    Oxidative stress and atherosclerosis: from LDL oxidation and foam cell formation to plaque instability – three decades of evidence and remaining therapeutic challenges · 2026 · DOI

  • However, the mechanisms through which the cuproptosis pathway contributes to macrophage foam cell formation remain unclear.

    Elesclomol Promotes oxLDL ‐Mediated Foam Cell Formation and Cuproptosis in Macrophages · 2026 · DOI

  • The basic mechanisms underlying early atherosclerosis remain controversial.

    Effect of colchicine administration on interleukin-1β and nitric oxide expression at the early stage of atherosclerosis in atherosclerosis Wistar rat model · 2025 · DOI

  • The underlying mechanisms, however, leading to increased risk of CVD due to metabolic cycling are not well understood.

    Cycling of metabolic states and metabolites as drivers of atherosclerosis · 2025 · DOI

  • Due to a lack of controlled studies, the capacity of arterial 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) uptake in patients with cancer to detect this arterial inflammation remains unclear.

    Longitudinal Assessment of Subclinical Arterial Inflammation in Patients Receiving Immune Checkpoint Inhibitors by Sequential [ 18 F]FDG PET Scans · 2025 · DOI

  • Melatonin reportedly plays a beneficial role in cardiovascular diseases; however, the mechanisms underlying improvements in atherosclerotic plaque vulnerability remain unknown.

    Melatonin Ameliorates Atherosclerotic Plaque Vulnerability by Regulating PPARδ‐Associated Smooth Muscle Cell Phenotypic Switching · 2024 · DOI

  • Recent evidence suggests a role of B cells in the pathogenesis of atherosclerosis; however, this relationship remains poorly understood, particularly in the context of HIV.

    B cells and atherosclerosis: A HIV perspective · 2024 · DOI

  • Currently, the timing for measurement of these biomarkers, particularly after an acute event, and overall utility of measuring these remain unclear.

    Inflammation: the next target for secondary prevention in coronary artery disease · 2024 · DOI

  • However, the effects and origination of CCs on endothelial inflammation in early atherogenesis are not well understood.

    Endothelial Cell-Derived Cholesterol Crystals Promote Endothelial Inflammation in Early Atherogenesis · 2024 · DOI

  • The transcriptional programs driving VSMC transitions are not well understood. The role of BHLHE40 in VSMC phenotype switching and foam cell formation is not well understood.

    Atherosclerosis Profiling Reveals BHLHE40 as a Candidate Modulator of VSMC · 2026 · DOI

  • The paper suggests that future research should focus on the development of personalized treatment strategies tailored to individual patient profiles. The paper also suggests that future research should investigate the safety and efficacy of nanomedicine delivery systems.

    Emerging biomedical and pharmaceutical strategies for the treatment of atherosclerosis: from conventional lipid-lowering therapy to nanomedicine · 2026 · DOI

  • The paper identifies a gap in the current treatment strategies for atherosclerosis, highlighting the need for more effective and personalized approaches. The paper also notes that there is a lack of understanding of the safety and efficacy of nanomedicine delivery systems.

    Emerging biomedical and pharmaceutical strategies for the treatment of atherosclerosis: from conventional lipid-lowering therapy to nanomedicine · 2026 · DOI

  • Prior studies have evaluated the prognostic value of other blood cell-derived indices, such as NLR and PLR, but not PIV.

    Prognostic Role of Pan-Immune-Inflammatory Value in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome · 2025 · DOI

  • The mechanistic links between Piezo1 and epigenetic modifications remain largely unexplored - Current evidence is insufficient to establish a direct causal role for Piezo1 in epigenetic regulation during…

    Piezo1 in atherosclerosis: a multifaceted mechanosensor bridging mechanotransduction, inflammation, and emerging therapies · 2026 · DOI

  • Investigating the mechanistic links between Piezo1 and epigenetic modifications - Exploring the role of Piezo1 in other cell types - Elucidating the context-dependent effects of Piezo1…

    Piezo1 in atherosclerosis: a multifaceted mechanosensor bridging mechanotransduction, inflammation, and emerging therapies · 2026 · DOI

  • Limitations in animal models, - Sex-related differences in plaque phenotype, - Lack of clinically applicable biomarkers, - Residual cardiovascular risk persists despite therapeutic…

    Atherosclerosis: From Pathogenesis to Therapeutic Interventions · 2026 · DOI

  • The interpretation of the results for the subgroups should be performed with caution due to the limited sample size within these strata, - Carotid artery ultrasound imaging is operator-dependent, - There are no universally accepted criteria for defining carotid atherosclerosis…

    Lipoprotein(a) and Blood Monocytes as Factors for Progression of Carotid Atherosclerosis in Patients with Premature Coronary Heart Disease · 2025 · DOI

  • Further validation of the findings is required before implementation in clinical practice, - Investigation of the therapeutic options for lipoprotein(a)…

    Lipoprotein(a) and Blood Monocytes as Factors for Progression of Carotid Atherosclerosis in Patients with Premature Coronary Heart Disease · 2025 · DOI

  • Further studies on the regulation of LOX-1 expression, - Investigation of the impact of anti-inflammatory agents on LOX-1 activation, - Research on the application of gene therapy to regulate LOX-1…

    LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review · 2024 · DOI

  • The therapeutic potential of aloin in atherosclerosis is not well understood - The underlying mechanisms of aloin in ameliorating atherosclerosis are insufficiently…

    Network pharmacology-based investigation on the mechanism of aloin in ameliorating atherosclerosis by regulating macrophage polarization · 2026 · DOI

  • This review identifies persistent gaps in knowledge and outlines future directions for research and therapeutic development.

    Oxidative stress and atherosclerosis: from LDL oxidation and foam cell formation to plaque instability – three decades of evidence and remaining therapeutic challenges · 2026 · DOI

Most-cited papers in Atherosclerosis and Cardiovascular Diseases

Most recent work

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Open questions raised by papers listed on this page include: (1) The paper highlights the challenge of establishing a therapeutic window for plaque-directed rapalog modulation, given the lack of cell-resolved relationships and the potential for nonlinear biological responses (“Context-dependent mTOR pharmacology in atherosclerotic plaque stability and…”, 2026); (2) Despite significant advances in understanding the pathophysiology, effective anti-atherosclerotic therapies targeting oxidative stress remain elusive (“Oxidative stress and atherosclerosis: from LDL oxidation and foam cell…”, 2026); (3) The mechanisms through which the cuproptosis pathway contributes to macrophage foam cell formation remain unclear (“Elesclomol Promotes oxLDL ‐Mediated Foam Cell Formation and Cuproptosis in…”, 2026); (4) The transcriptional programs driving VSMC transitions are not well understood (“Atherosclerosis Profiling Reveals BHLHE40 as a Candidate Modulator of VSMC”, 2026); (5) The paper suggests that future research should focus on the development of personalized treatment strategies tailored to individual patient profiles (“Emerging biomedical and pharmaceutical strategies for the treatment of…”, 2026). 321 gap statements have been mined from Atherosclerosis and Cardiovascular Diseases papers in our 7.9M-paper local library, which holds 1,414 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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