ArticleJACC. Basic to translational science2022
Dynamic Multiscale Regulation of Perfusion Recovery in Experimental Peripheral Arterial Disease: A Mechanistic Computational Model.
Article in JACC. Basic to translational science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 16 citations in OpenAlex.
- Experimental and computational studies of IL-6 signaling in endothelial cells under hypoxia serum starvation conditions.Cytokine · 2025Article
- Mechanistic data-informed multiscale quantitative systems pharmacology modeling framework enables the clinical translation and efficacy assessment of CAR-T therapy in solid tumors.Journal for immunotherapy of cancer · 2025Article
- The molecular mechanisms and therapeutic implications of PANoptosis in ischemic diseases.Apoptosis : an international journal on programmed cell death · 2025Review
- A mechanistic computational model of HGF-VEGF-mediated endothelial cell proliferation and vascular permeability.iScience · 2025Article
- Promoting vascular stability through Src inhibition and Tie2 activation: A model-based analysis.iScience · 2025Article
- Biomarkers of mRNA vaccine efficacy derived from mechanistic modeling of tumor-immune interactions.PLoS computational biology · 2025Article
- A mechanistic quantitative systems pharmacology model platform for translational efficacy evaluation and checkpoint combination design of bispecific immuno-modulatory antibodies.Frontiers in pharmacology · 2025Article
- Computational modeling of drug-eluting balloons in peripheral artery disease: Mechanisms, optimization, and translational insights.Computational and structural biotechnology journal · 2025Review
- Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.Acta pharmacologica Sinica · 2024Article
- Signaling-biophysical modeling unravels mechanistic control of red blood cell phagocytosis by macrophages in sickle cell disease.PNAS nexus · 2024Article
- An In Silico Platform to Predict Cardiotoxicity Risk of Anti-tumor Drug Combination with hiPSC-CMs Based In Vitro Study.Pharmaceutical research · 2024Article
- Systems-level computational modeling in ischemic stroke: from cells to patients.Frontiers in physiology · 2024Review
- Experiment-based computational model predicts that IL-6 classic and trans-signaling exhibit similar potency in inducing downstream signaling in endothelial cells.NPJ systems biology and applications · 2023Article
- Experiment-based Computational Model Predicts that IL-6 Trans-Signaling Plays a Dominant Role in IL-6 mediated signaling in Endothelial Cells.bioRxiv : the preprint server for biology · 2023Article
- Systems biology of angiogenesis signaling: Computational models and omics.WIREs mechanisms of disease · 2022Review
- New Insights in Peripheral Arterial Disease: Novel In Silico Mouse and Disease-Based Computational Models.JACC. Basic to translational science · 2022Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
In peripheral arterial disease (PAD), the degree of endogenous capacity to modulate revascularization of limb muscle is central to the management of leg ischemia. To characterize the multiscale and multicellular nature of revascularization in PAD, we have developed the first computational systems biology model that mechanistically incorporates intracellular, cellular, and tissue-level features critical for the dynamic reconstitution of perfusion after occlusion-induced ischemia. The computational model was specifically formulated for a preclinical animal model of PAD (mouse hindlimb ischemia [HLI]), and it has gone through multilevel model calibration and validation against a comprehensive set of experimental data so that it accurately captures the complex cellular signaling, cell-cell communication, and function during post-HLI perfusion recovery. As an example, our model simulations generated a highly detailed description of the time-dependent spectrum-like macrophage phenotypes in HLI, and through model sensitivity analysis we identified key cellular processes with potential therapeutic significance in the pathophysiology of PAD. Furthermore, we computationally evaluated the in vivo effects of different targeted interventions on post-HLI tissue perfusion recovery in a model-based, data-driven, virtual mouse population and experimentally confirmed the therapeutic effect of a novel model-predicted intervention in real HLI mice. This novel multiscale model opens up a new avenue to use integrative systems biology modeling to facilitate translational research in PAD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.