Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation
- University of Illinois at Chicago, United States
Abstract
Blood vessels are lined by endothelial cells engaged in distinct organ-specific functions but little is known about their characteristic gene expression profiles. RNA-Sequencing of the brain, lung, and heart endothelial translatome identified specific pathways, transporters and cell-surface markers expressed in the endothelium of each organ, which can be visualized at http://www.rehmanlab.org/ribo. We found that endothelial cells express genes typically found in the surrounding tissues such as synaptic vesicle genes in the brain endothelium and cardiac contractile genes in the heart endothelium. Complementary analysis of endothelial single cell RNA-Seq data identified the molecular signature shared across the endothelial translatome and single cell transcriptomes. The tissue-specific heterogeneity of the endothelium is maintained during systemic in vivo inflammatory injury as evidenced by the distinct responses to inflammatory stimulation. Our study defines endothelial heterogeneity and plasticity and provides a molecular framework to understand organ-specific vascular disease mechanisms and therapeutic targeting of individual vascular beds.
Data availability
RNA Sequencing data have been deposited in GEO under accession code GSE136848We downloaded Tabula Muris data from https://github.com/czbiohub/tabula-muris and Betsholtz Lab data from NCBI Gene Expression Omnibus (GSE99235, GSE98816)
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Single cell RNA-seq of mouse lung vascular transcriptomesNCBI Gene Expression Omnibus, GSE99235.
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Single cell RNA-seq of mouse brain vascular transcriptomesNCBI Gene Expression Omnibus, GSE98816.
Article and author information
Author details
Funding
National Institutes of Health (R01HL126516)
- Jalees Rehman
National Institutes of Health (P01-HL60678)
- Asrar B Malik
- Jalees Rehman
National Institutes of Health (T32-HL007829)
- Asrar B Malik
National Institutes of Health (R01-HL90152)
- Asrar B Malik
- Jalees Rehman
American Heart Association (18CDA34110068)
- Lianghui Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were conducted in accordance with NIH guidelines for the Care and Use of Laboratory Animals and were performed in accordance with protocols approved by the Institutional Animal Care and Use Committees (IACUC) of the University of Illinois (protocol approval numbers 19-014, 13-175 and 16-064) .
Reviewing Editor
- Anna Akhmanova, Utrecht University, Netherlands
Publication history
- Received: August 27, 2019
- Accepted: January 15, 2020
- Accepted Manuscript published: January 16, 2020 (version 1)
- Version of Record published: February 5, 2020 (version 2)
Copyright
© 2020, Jambusaria et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation
eLife 9:e51413.
https://doi.org/10.7554/eLife.51413
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Background: Although inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed.
Methods: We enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests.
Results: Our results revealed that binding antibody IgM peaked 14-28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The neutralized fraction subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89) to 17.8% (16/90).
Conclusions: Two doses of CoronaVac vaccine resulted in limited protection over a short duration. The inactivated vaccine booster can reverse the decrease of antibody levels to prime strain, but it does not elicit potent neutralization against Omicron; therefore, the optimization of booster procedures is vital.
Funding: Key Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation; Explorer Program of Zhejiang Municipal Natural Science Foundation.
