Back to Search
Start Over
Endothelial KLF11 is a novel protector against diabetic atherosclerosis.
- Source :
-
Cardiovascular Diabetology . 10/26/2024, Vol. 23 Issue 1, p1-21. 21p. - Publication Year :
- 2024
-
Abstract
- Background: Atherosclerotic cardiovascular diseases remain the leading cause of mortality in diabetic patients, with endothelial cell (EC) dysfunction serving as the initiating step of atherosclerosis, which is exacerbated in diabetes. Krüppel-like factor 11 (KLF11), known for its missense mutations leading to the development of diabetes in humans, has also been identified as a novel protector of vascular homeostasis. However, its role in diabetic atherosclerosis remains unexplored. Methods: Diabetic atherosclerosis was induced in both EC-specific KLF11 transgenic and knockout mice in the Ldlr−/− background by feeding a diabetogenic diet with cholesterol (DDC). Single-cell RNA sequencing (scRNA-seq) was utilized to profile EC dysfunction in diabetic atherosclerosis. Additionally, gain- and loss-of-function experiments were conducted to investigate the role of KLF11 in hyperglycemia-induced endothelial cell dysfunction. Results: We found that endothelial KLF11 deficiency significantly accelerates atherogenesis under diabetic conditions, whereas KLF11 overexpression remarkably inhibits it. scRNA-seq profiling demonstrates that loss of KLF11 increases endothelial-to-mesenchymal transition (EndMT) during atherogenesis under diabetic conditions. Utilizing gain- and loss-of-function approaches, our in vitro study reveals that KLF11 significantly inhibits EC inflammatory activation and TXNIP-induced EC oxidative stress, as well as Notch1/Snail-mediated EndMT under high glucose exposure. Conclusion: Our study demonstrates that endothelial KLF11 is an endogenous protective factor against diabetic atherosclerosis. These findings indicate that manipulating KLF11 could be a promising approach for developing novel therapies for diabetes-related cardiovascular complications. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14752840
- Volume :
- 23
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cardiovascular Diabetology
- Publication Type :
- Academic Journal
- Accession number :
- 180500562
- Full Text :
- https://doi.org/10.1186/s12933-024-02473-y