Multiple pathway assessment to predict anti-atherogenic efficacy of drugs targeting macrophages in atherosclerotic plaques

Amr Muhmed Sabry Abdelhakeem Alaarg, K.H. Zheng, F.M. van der Valk, Acarilia Eduardo Da Silva, M. Versloot, Linda C. Quarles van Ufford, D.M. Schulte, Gerrit Storm, Josbert Maarten Metselaar, E.S. Stroes, A.A.J. Hamers

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Background Macrophages play a central role in atherosclerosis development and progression, hence, targeting macrophage activity is considered an attractive therapeutic. Recently, we documented nanomedicinal delivery of the anti-inflammatory compound prednisolone to atherosclerotic plaque macrophages in patients, which did however not translate into therapeutic efficacy. This unanticipated finding calls for in-depth screening of drugs intended for targeting plaque macrophages. Methods and results We evaluated the effect of several candidate drugs on macrophage activity, rating overall performance with respect to changes in cytokine release, oxidative stress, lipid handling, endoplasmic reticulum (ER) stress, and proliferation of macrophages. Using this in vitro approach, we observed that the anti-inflammatory effect of prednisolone was counterbalanced by multiple adverse effects on other key pathways. Conversely, pterostilbene, T0901317 and simvastatin had an overall anti-atherogenic effect on multiple pathways, suggesting their potential for liposomal delivery. Conclusion This dedicated assay setup provides a framework for high-throughput assessment. Further in vivo studies are warranted to determine the predictive value of this macrophage-based screening approach and its potential value in nanomedicinal drug development for cardiovascular patients.
Original languageUndefined
Pages (from-to)51-59
JournalVascular pharmacology
Volume82
DOIs
Publication statusPublished - 2016

Keywords

  • METIS-320764
  • IR-103380

Cite this

Alaarg, A. M. S. A., Zheng, K. H., van der Valk, F. M., Eduardo Da Silva, A., Versloot, M., Quarles van Ufford, L. C., ... Hamers, A. A. J. (2016). Multiple pathway assessment to predict anti-atherogenic efficacy of drugs targeting macrophages in atherosclerotic plaques. Vascular pharmacology, 82, 51-59. https://doi.org/10.1016/j.vph.2016.04.006