Purpose: Atherosclerosis and its related clinical complications are the leading cause of death. MicroRNA (miR)-92a in the inflammatory endothelial dysfunction leads to atherosclerosis. Krüppel-like factor 2 (KLF2) is required for vascular integrity and endothelial function maintenance. Flavonoids possess many biological properties. This study investigated the vascular protective effects of chrysin in balloon-injured carotid arteries.
Materials And Methods: Exosomes were extracted from human coronary artery endothelial cell (HCAEC) culture media. Herb flavonoids and chrysin were the treatments in these atheroprotective models. Western blotting and real-time PCRs were performed. In situ hybridization, immunohistochemistry, and immunofluorescence analyses were employed.
Results: MiR-92a increased after balloon injury and was present in HCAEC culture media. Chrysin was treated, and significantly attenuated the miR-92a levels after balloon injury, and similar results were obtained in HCAEC cultures in vitro. Balloon injury-induced miR-92a expression, and attenuated KLF2 expression. Chrysin increased the KLF2 but reduced exosomal miR-92a secretion. The addition of chrysin and antagomir-92a, neointimal formation was reduced by 44.8 and 49.0% compared with balloon injury after 14 days, respectively.
Conclusion: Chrysin upregulated KLF2 expression in atheroprotection and attenuated endothelial cell-derived miR-92a-containing exosomes. The suppressive effect of miR-92a suggests that chrysin plays an atheroprotective role. Proposed pathway for human coronary artery endothelial cell (HCAEC)-derived exosomes induced by chrysin to suppress microRNA (miR)-92a expression and counteract the inhibitory effect of miR-92a on KLF2 expression in HCAECs. This provides an outline of the critical role of the herbal flavonoid chrysin, which may serve as a valuable therapeutic supplement for atheroprotection.
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http://dx.doi.org/10.1007/s00394-021-02593-1 | DOI Listing |
Int Immunopharmacol
January 2025
Zhejiang Provincial Clinical Research Center for Pediatric Disease, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address:
Coronary artery lesions constitute a significant complication of Kawasaki disease (KD) and represents one of the primary etiologies of acquired cardiovascular disease in pediatric populations. In the present study, we observed a downregulation of MEF2C expression in the whole blood of KD patients and in human coronary artery endothelial cells (HCAECs) during the pathophysiological progression of KD. Furthermore, transcriptomic data analysis, in conjunction with observations from HCAECs stimulated with KD serum, indicates that the downregulation of MEF2C in KD is correlated with increased inflammatory levels and the activation of inflammatory pathways.
View Article and Find Full Text PDFIschemic stroke (IS) often causes fearful sequela, even death. Curcumin was beneficial to IS, but its underlying molecular mechanism is unclear. Mice were subjected to middle cerebral artery occlusion (MCAO) surgery, and BV-2 cells were treated with oxygen-glucose deprivation/reoxygenation (OGD/R) induction to establish IS models in vivo and in vitro.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Experimental Medicine, Tor Vergata University of Rome, 00133 Rome, Italy.
MicroRNA (miR)-126 is frequently downregulated in malignancies, including breast cancer (BC). Despite its tumor-suppressive role, the mechanisms underlying miR-126 deregulation in BC remain elusive. Through silencing experiments, we identified Early B Cell Factor 1 (EBF1), ETS Proto-Oncogene 2 (ETS2), and Krüppel-Like Factor 2 (KLF2) as pivotal regulators of miR-126 expression.
View Article and Find Full Text PDFBiomedicines
November 2024
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, University of Montréal, Montréal, QC H1T 2M4, Canada.
Choroidal involution is a common feature of age-related ischemic retinopathies such as age-related macular degeneration (AMD). It is now well recognized that endothelial progenitor cells (EPCs) are essential to endothelial repair processes and in maintaining vascular integrity. However, the contribution of EPCs and the role of senescence in age-related choroidal vascular degeneration remain to be investigated.
View Article and Find Full Text PDFJ Mol Cell Cardiol
December 2024
Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen 518057, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; Key Laboratory of Application of Pluripotent Stem Cells in Heart Regeneration, Chinese Academy of Medical Sciences, Beijing 100037, China. Electronic address:
Background: Our previous single-cell RNA sequencing study in the adult human heart revealed that cardiomyocytes from both the atrium and ventricle display high activities of Krüppel-like factor 2 (KLF2) regulons. However, the role of the transcription factor KLF2 in cardiomyocyte biology remains largely unexplored.
Methods And Results: We employed transverse aortic constriction surgery in male C57BL/6 J mice to develop an in vivo model of cardiac hypertrophy, and generated different in vitro cardiac hypertrophy models in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes.
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