/2020_georgakis_vanderlaan_MCP1

Monocyte-chemoattractant protein-1 Levels in Human Atherosclerosis Associate with Plaque Vulnerability

Primary LanguageHTMLMIT LicenseMIT

Monocyte-chemoattractant protein-1 Levels in Human Atherosclerosis Associate with Plaque Vulnerability

DOI

This readme

This readme accompanies the paper "Monocyte-chemoattractant protein-1 Levels in Human Atherosclerosis Associate with Plaque Vulnerability." by Georgakis M. & van der Laan S.W. et al. bioRxiv 2020.

Abstract

Marios K. Georgakis,1, a Sander W. van der Laan,2, a Yaw Asare,1 Joost M. Mekke,3 Saskia Haitjema,4 Arjan H. Schoneveld,4 Dominique P.V. de Kleijn,3 Gert J. de Borst,3 Gerard Pasterkamp,4 Martin Dichgans1, 5, *

1 Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany 2 Laboratory of Experimental Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands 3 Department of Vascular Surgery, Division of Surgical Specialties, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands 4 Center Diagnostic Laboratory, Division Laboratories and Pharmacy, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands 5 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

a contributed equally

Monocyte chemoattractant protein-1 (MCP-1) recruits monocytes to the atherosclerotic plaque. While experimental,1-6 genetic,7 and observational8,9 data support a key role of MCP-1 in atherosclerosis, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Here, we measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy and explored associations with histopathological, molecular, and clinical features of plaque vulnerability. MCP-1 plaque levels were associated with histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage) as well as molecular markers of plaque inflammation and matrix turnover, clinical plaque instability, and periprocedural stroke during plaque removal. Collectively, our findings highlight a role of MCP-1 in human plaque vulnerability and suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.

Figure 1 Figure 1. Design of this study.

Analysis Scripts

These scripts will not work immediately on your systems, but they are easily edited for local use given the required data.

Epidemiological study

  • 2020_georgakis_vanderlaan_MCP1.01.main_analysis.Rmd
    R Notebook in R markdown with all steps taken, double checks on data, and analysis of the manuscript.
  • 2020_georgakis_vanderlaan_MCP1.01.main_analysis.nb.html
    R Notebook in HTML the compiled R markdown notebook for easy reading in any browser.

Additional figures

  • 2020_georgakis_vanderlaan_MCP1.02.additional_figures.Rmd
    R Notebook in R markdown for additional figures and (sub-)analyses.
  • 2020_georgakis_vanderlaan_MCP1.02.additional_figures.nb.html
    R Notebook in HTML the compiled R markdown notebook for easy reading in any browser.

Review comments

  • 2020_georgakis_vanderlaan_MCP1.03.review_comments.Rmd
    R Notebook in R markdown that addresses some of the reviewer comments.
  • 2020_georgakis_vanderlaan_MCP1.03.review_comments.nb.html
    R Notebook in HTML the compiled R markdown notebook for easy reading in any browser.

scRNAseq analysis for the reviewer comments

  • scRNAseq/scRNAseq.Rmd
    R Notebook in R markdown with all steps taken, double checks on data, and analysis of scRNAseq data.
  • scRNAseq/scRNAseq.nb.html
    R Notebook in HTML the compiled R markdown notebook of the scRNAseq analysis for easy reading in any browser.

Data availability

The data is available upon request through a MTA/DTA due to consent restrictions and EU/NL laws and regulations.

Notes

The code will work within the context of R version 3.5.2 (2018-12-20) -- 'Eggshell Igloo' with macOS Mojave (10.14.2); and given the data (see section Data availability).

Versions

  • v1.0.3 Addressed reviewer comments. Redesigned the notebooks. Fixed notebooks to properly compile and show output.
  • v1.0.2 Submission release with update license type.
  • v1.0.1 Zenodo release, bares no difference to v1.0.0.
  • v1.0.0 Initial version.

The MIT License (MIT)

Copyright (c) 1979-present Sander W. van der Laan | s.w.vanderlaan [at] gmail [dot] com.

Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions:

The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software.

THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE.

Reference: http://opensource.org.