Identification of unannotated microproteins involved in endothelial cell homeostasis, dysfunction and vascular disease
Clicks: 1
ID: 314246
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
0.0
/100
1 views
0 readers
AI Quality Assessment
Not analyzed
Readership in this journal
Ranked #76 of 103 articles by views in cardiovascular research
Most read
Least read
Bar heights use a square-root scale.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
AIMS: Microproteins (miPs) translated from small open reading frames (smORFs) are crucial regulators of cell function. However, the expression and function of miPs in endothelial cells, and alterations in miP expression linked with inflammation and cardiovascular disease, remain largely unexplored. METHODS AND RESULTS: An optimized proteo-genomic approach combining RiboTag RNA-sequencing and mass spectrometry of the small molecular mass proteome was utilized to identify endothelial cell-specific miPs. Heart, lung and blood vessels from endothelial cell-specific RiboTag mice and human endothelial cells were studied under homeostatic and inflammatory conditions. We identified 2,739 murine as well as 1,365 intracellular and 607 extracellular human endothelial cell miPs encoded from previously unannotated non-canonical smORFs. Vascular inflammation induced in vitro by interleukin-1β and in vivo through PCSK9 overexpression, high fat diet and partial carotid artery ligation, significantly altered smORF expression. An additional 347 miPs were detected in human serum, 23 decreasing and 31 increasing after cardiac damage. The expression of an inflammation-induced miP encoded by an internal smORF within the proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) transcript, i.e. miP-PSTPIP2, was assessed using a custom antibody. miP-PSTPIP2 expression was upregulated in IL-1β-treated human endothelial cells, in pre-atherosclerotic murine carotid arteries and detected in carotid arteries from patients with atherosclerosis. The relevance of 250 miPs for endothelial cell growth and viability was demonstrated using a high-throughput CRISPR/Cas9 screen. CONCLUSIONS: Taken together, we document the existence of a large number of human and murine miPs encoded by non-canonical smORFs and their altered expression in inflammatory conditions. The identification of secreted miPs suggests that they may also exert autocrine or paracrine functions. These novel small peptides modulate cell proliferation and survival in endothelial cells and may play a significant role in human cardiovascular disease.
| Reference Key |
openalex_W7161796305
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Mauro Siragusa, Johannes Graumann, Carsten Kuenne, Stefan Günther, Sylvia Jeratsch, Beyza Güven, Sebastian Süsser, Sweta Talyan, Bethlehem Bezuneh, Yves Matthess, Matteo Cartura, Xiaozhu Zhou, Haaglim Cho, Nadja Sachs, Lars Mäegdefessel, Oliver J Müller, Christian Troidl, Holger Nef, Mario Looso, Manuel Kaulich, Stefan Offermanns, Ingrid Fleming |
| Journal | cardiovascular research |
| Year | 2026 |
| DOI |
10.1093/cvr/cvag110
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.