Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE
Abstract Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the sm...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-82190-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585900971786240 |
|---|---|
| author | Lihong Huo Arati Naveen Kumar Gantsetseg Tumurkhuu Moumita Bose Daniel S. Berman Daniel J. Wallace Janet Wei Mariko Ishimori C. Noel Bairey Merz Caroline Jefferies |
| author_facet | Lihong Huo Arati Naveen Kumar Gantsetseg Tumurkhuu Moumita Bose Daniel S. Berman Daniel J. Wallace Janet Wei Mariko Ishimori C. Noel Bairey Merz Caroline Jefferies |
| author_sort | Lihong Huo |
| collection | DOAJ |
| description | Abstract Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n = 4) from those without (n = 7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. RNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and healthy control (HC) groups, with virus defense and interferon (IFN) signaling being the key pathways identified as enriched in SLE as expected. We next conducted a comparative analysis of genes differentially expressed in SLE–CMD and SLE–non-CMD relative to HC samples. Our analysis highlighted differences in IFN signaling, RNA sensing and ADP-ribosylation pathways between SLE–CMD and SLE–non-CMD. This is the first study to investigate possible gene signatures associating with CMD in SLE, and our data strongly suggests that distinct molecular mechanisms underly vascular changes in CMD and non-CMD involvement in SLE. |
| format | Article |
| id | doaj-art-29c72e1a298a4bc4a31f6d98c6d54665 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-29c72e1a298a4bc4a31f6d98c6d546652025-01-26T12:24:32ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-024-82190-4Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLELihong Huo0Arati Naveen Kumar1Gantsetseg Tumurkhuu2Moumita Bose3Daniel S. Berman4Daniel J. Wallace5Janet Wei6Mariko Ishimori7C. Noel Bairey Merz8Caroline Jefferies9Division of Rheumatology, Department of Medicine, Cedars-Sinai Medical CenterDivision of Rheumatology, Department of Medicine, Cedars-Sinai Medical CenterDivision of Rheumatology, Department of Medicine, Cedars-Sinai Medical CenterDivision of Rheumatology, Department of Medicine, Cedars-Sinai Medical CenterS. Mark Taper Foundation Imaging Center, Cedars-Sinai Medical CenterDivision of Rheumatology, Department of Medicine, Cedars-Sinai Medical CenterDepartment of Cardiology, Cedars-Sinai Medical CenterDivision of Rheumatology, Department of Medicine, Cedars-Sinai Medical CenterDepartment of Cardiology, Cedars-Sinai Medical CenterDivision of Rheumatology, Department of Medicine, Cedars-Sinai Medical CenterAbstract Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n = 4) from those without (n = 7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. RNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and healthy control (HC) groups, with virus defense and interferon (IFN) signaling being the key pathways identified as enriched in SLE as expected. We next conducted a comparative analysis of genes differentially expressed in SLE–CMD and SLE–non-CMD relative to HC samples. Our analysis highlighted differences in IFN signaling, RNA sensing and ADP-ribosylation pathways between SLE–CMD and SLE–non-CMD. This is the first study to investigate possible gene signatures associating with CMD in SLE, and our data strongly suggests that distinct molecular mechanisms underly vascular changes in CMD and non-CMD involvement in SLE.https://doi.org/10.1038/s41598-024-82190-4InterferonCoronary microvascular diseaseGene expressionSystemic lupus erythematosus |
| spellingShingle | Lihong Huo Arati Naveen Kumar Gantsetseg Tumurkhuu Moumita Bose Daniel S. Berman Daniel J. Wallace Janet Wei Mariko Ishimori C. Noel Bairey Merz Caroline Jefferies Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE Scientific Reports Interferon Coronary microvascular disease Gene expression Systemic lupus erythematosus |
| title | Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE |
| title_full | Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE |
| title_fullStr | Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE |
| title_full_unstemmed | Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE |
| title_short | Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE |
| title_sort | alterations in genes associated with cytosolic rna sensing in whole blood are associated with coronary microvascular disease in sle |
| topic | Interferon Coronary microvascular disease Gene expression Systemic lupus erythematosus |
| url | https://doi.org/10.1038/s41598-024-82190-4 |
| work_keys_str_mv | AT lihonghuo alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle AT aratinaveenkumar alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle AT gantsetsegtumurkhuu alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle AT moumitabose alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle AT danielsberman alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle AT danieljwallace alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle AT janetwei alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle AT marikoishimori alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle AT cnoelbaireymerz alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle AT carolinejefferies alterationsingenesassociatedwithcytosolicrnasensinginwholebloodareassociatedwithcoronarymicrovasculardiseaseinsle |