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Updated: Jun 3, 2025
Author Spotlight: Accelerating Research on Bacterial Extracellular Vesicles Separation and Heterogeneity
Published on: September 1, 2023
Klebsiella pneumoniae-derived extracellular vesicles impair endothelial function by inhibiting SIRT1
Xinxin Li1, Jinghua Cui2, Zanbo Ding2
1Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling Cardiovascular Diseases, Ministry of Education; Collaborative Innovation Center for Cardiovascular Disorders, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, 100029, China.
Background:
The potential role of Klebsiella pneumoniae (K.pn) in hypertension development has been emphasized, although the specific mechanisms have not been well understood. Bacterial extracellular vesicles (BEVs) released by Gram-negative bacteria modulate host cell functions by delivering bacterial components to host cells. Endothelial dysfunction is an important early event in the pathogenesis of hypertension, yet the impact of K.pn-secreted EVs (K.pn EVs) on endothelial function remains unclear. This study aimed to investigate the effects of K.pn EVs on endothelial function and to elucidate the underlying mechanisms.
Methods:
K.pn EVs were purified from the bacterial suspension using ultracentrifugation and characterized by transmission electron microscopy nanoparticle tracking analysis, and EV marker expression. Endothelium-dependent relaxation was measured using a wire myograph after in vivo or ex vivo treatment with K.pn EVs. Superoxide anion production was measured by confocal microscopy and HUVEC senescence was assessed by SA-β-gal activity. SIRT1 overexpression or activator was utilized to investigate the underlying mechanisms.
Results:
Our data showed that K.pn significantly impaired acetylcholine-induced endothelium-dependent relaxation and increased superoxide anion production in endothelial cells in vivo. Similarly, in vivo and ex vivo studies showed that K.pn EVs caused significant endothelial dysfunction, endothelial provocation, and increased blood pressure. Further examination revealed that K.pn EVs reduced the levels of SIRT1 and p-eNOS and increased the levels of NOX2, COX-2, ET-1, and p53 in endothelial cells. Notably, overexpression or activation of SIRT1 attenuated the adverse effects and protein changes induced by K.pn EVs on endothelial cells.
Conclusion:
This study reveals a novel role of K.pn EVs in endothelial dysfunction and dissects the relevant mechanism involved in this process, which will help to establish a comprehensive understanding of K.pn EVs in endothelial dysfunction and hypertension from a new scope.
