CD38⁺ endothelial remodeling marks spatially patterned vasculopathy in rapidly advancing periodontitis and peri-implantitis
vascular endothelial cell (VEC) rarefaction and oxidative stress, hypoxia, and NAD⁺ metabolism-associated transcriptional programs enriched in a TNFRSF6B⁺/ICAM1⁺ post-capillary venule (PC-VEC) subpopulation. NAD⁺-consuming ectoenzyme CD38 was selectively enriched and orthogonally confirmed by spatial transcriptomics (6-samples; 283,377-cells) and proteomics (23-samples; 562,397-cells). Spatial neighborhood analyses demonstrated CD38⁺-high PC-VEC expansion, closer proximity, and higher IL16-CD4 T cell signaling in peri-implantitis. Matched high-grade periodontitis biopsies confirmed spatially restricted CD38⁺-VECs despite similar microbial burden, identifying endothelial vasculopathy underlying rapidly advancing oral inflammation and a potential therapeutic axis.
Authors
- Quinn T. Easter (ORCID: https://orcid.org/0000-0002-8018-0405)
- Nivedita Pareek
- Camila S. Stolf (ORCID: https://orcid.org/0000-0002-5125-2326)
- Zhaoxu Chen (ORCID: https://orcid.org/0000-0002-8276-2206)
- Akira Hasuike (ORCID: https://orcid.org/0000-0001-5150-2076)
- Zabdiel Alvarado‐Martinez (ORCID: https://orcid.org/0000-0002-6581-3139)
- Renato Casarin
- Kevin M. Byrd (ORCID: https://orcid.org/0000-0002-5565-0524)
- Kang I. Ko (ORCID: https://orcid.org/0000-0003-2967-8846)
- Di Wu (ORCID: https://orcid.org/0000-0002-3391-5456)
- Jinze Liu (ORCID: https://orcid.org/0000-0003-0555-9412)
- Jialiu Xie (ORCID: https://orcid.org/0000-0002-0560-7982)
- Bruno Fernandes Matuck
- William S Kim
- Apoena Aguiar Ribeiro
- Khoa L A Huynh
- Andrea M Azcarate-Peril
Institutions
- Nihon University (JP)
- University of North Carolina at Chapel Hill (US)
- University of California, San Francisco (US)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Virginia Commonwealth University (US)
- University of Dental Medicine (MM)
- Independent Sector (US)
- University at Buffalo, State University of New York (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-08
- DOI
- https://doi.org/10.1038/s41467-026-72452-2
- Primary Topic
- Calcium signaling and nucleotide metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00