SVEP1 is an endogenous ligand for the orphan receptor PEAR1

Jared S. Elenbaas (), Upasana Pudupakkam, Katrina J. Ashworth, Chul Joo Kang, Ved Patel, Katherine Santana, In-Hyuk Jung, Paul C. Lee, Kendall H. Burks, Junedh M. Amrute, Robert P. Mecham, Carmen M. Halabi, Arturo Alisio, Jorge Paola and Nathan O. Stitziel ()
Additional contact information
Jared S. Elenbaas: Washington University School of Medicine
Upasana Pudupakkam: Washington University School of Medicine
Katrina J. Ashworth: Washington University in St. Louis
Chul Joo Kang: Washington University School of Medicine
Ved Patel: Washington University School of Medicine
Katherine Santana: Washington University School of Medicine
In-Hyuk Jung: Washington University School of Medicine
Paul C. Lee: Washington University School of Medicine
Kendall H. Burks: Washington University School of Medicine
Junedh M. Amrute: Washington University School of Medicine
Robert P. Mecham: Washington University School of Medicine
Carmen M. Halabi: Washington University School of Medicine
Arturo Alisio: Washington University School of Medicine
Jorge Paola: Washington University in St. Louis
Nathan O. Stitziel: Washington University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease and associates with platelet reactivity in humans. Here, using a human genomic and proteomic approach, we identify a high affinity, disease-relevant, and potentially targetable interaction between SVEP1 and the orphan receptor Platelet and Endothelial Aggregation Receptor 1 (PEAR1). This interaction promotes PEAR1 phosphorylation and disease associated AKT/mTOR signaling in vascular cells and platelets. Mice lacking SVEP1 have reduced platelet activation, and exogenous SVEP1 induces PEAR1-dependent activation of platelets. SVEP1 and PEAR1 causally and concordantly relate to platelet phenotypes and cardiovascular disease in humans, as determined by Mendelian Randomization. Targeting this receptor-ligand interaction may be a viable therapeutic strategy to treat or prevent cardiovascular and thrombotic disease.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36486-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36486-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36486-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().