Complement C1q and von Willebrand factor interaction in atherosclerosis of human carotid artery

Kristina Schulz; Claudia Donat; Mukesh Punjabi; Katharina Glatz; Beat Kaufmann; Marten Trendelenburg

doi:10.3389/fimmu.2023.1265387

Complement C1q and von Willebrand factor interaction in atherosclerosis of human carotid artery

Front Immunol. 2023 Dec 14:14:1265387. doi: 10.3389/fimmu.2023.1265387. eCollection 2023.

Authors

Kristina Schulz^#^{1

2}, Claudia Donat^#¹, Mukesh Punjabi³, Katharina Glatz⁴, Beat Kaufmann⁵, Marten Trendelenburg^{1

2}

Affiliations

¹ Laboratory of Clinical Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
² Division of Internal Medicine, University Hospital of Basel, Basel, Switzerland.
³ Laboratory of Cardiovascular Molecular Imaging, Department of Biomedicine, University of Basel, Basel, Switzerland.
⁴ Institute for Pathology, University Hospital of Basel, Basel, Switzerland.
⁵ Division of Cardiology, University Hospital of Basel, Basel, Switzerland.

^# Contributed equally.

Abstract

Atherosclerosis is an inflammatory disease of the vessel wall, with cholesterol crystal (CC) deposition being a hallmark of the disease. As evidence for a cross-talk between complement activation and hemostasis on CC surfaces has been limited to in vitro data, the aim of this study was to demonstrate the presence of C1q-vWF complexes in human atherosclerosis ex vivo. We used immunofluorescence staining and a proximity ligation assay (PLA, Duolink^®) to examine the presence, localization, and co-localization of C1q and vWF in frozen sections of human carotid arteries with atherosclerosis or without atherosclerotic changes as well as material from thrombendarteriectomy. We observed significantly higher levels of C1q and vWF in healthy tissue compared to diseased material and greater co-localization in the PLA in healthy samples than in diseased samples. In diseased samples, fluorescence signals were highest in locations encompassing atheroma and foam cells. While there was overall reduced signal in areas with CCs, the staining was spotty, and there was evidence of co-localization on individual CCs. Thus, we demonstrate the presence of C1q-vWF complexes in human carotid arteries ex vivo, which was most abundant in healthy endothelial and subendothelial space and reduced in diseased tissue. C1q-vWF interaction can also be demonstrated on the CC surface.

Keywords: C1q; atherosclerosis; complement; hemostasis; vWF; von Willebrand factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis*
Carotid Arteries
Complement C1q
Humans
Plaque, Atherosclerotic*
von Willebrand Factor

Substances

von Willebrand Factor
Complement C1q

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work was funded by a project grant from the Swiss National Science Foundation (Grant No. 320030_200423).