Background: Tearing of inner layer of aorta causes aortic dissection (AD), a severe disease with high morbidity and mortality. The pathological development of AD partially results from apoptotic death of aortic endothelial cells (AECs), the trigger and the molecular regulation of which remain largely unknown. Cyclin-dependent kinase 5 (CDK5) was initially detected in the brain as a proline-directed serine/threonine protein kinase regulating neuronal cell cycle re-entry and arrest. The abnormal expression of CDK5 leads to apoptotic cell death following abortive cell cycle re-entry in some neuronal diseases. Although physiological and pathological roles of CDK5 have been widely investigated, the expression and function of CDK5 in AD have not been reported. Therefore, the aim of the present study was to discuss the expression and function of CDK5 in AD.
Methods: Gene expression profiles were compared between AD tissues and normal aortic tissues using Gene Expression Omnibus (GEO) database with bioinformatic tools. Different cell types were isolated from the digested AD and normal aortic specimens by fluorescence-activated cell sorting (FACS). Gene expression in cells was quantified by quantitative reverse transcription polymerase chain reaction. Endothelial cells purified by FACS were transfected with plasmids. Cell growth was analyzed by Cell Counting Kit-8 assay. Cell apoptosis was analyzed by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assay.
Results: Analysis of gene profiles from AD tissues and normal aortic tissues using GEO database showed significant higher expression of CDK5 and its downstream regulated genes, proliferating cell nuclear antigen, cyclin B1, and B-cell lymphoma 2, which are regulators for cell cycle and apoptosis. Analysis of purified cells from AD and normal aortic specimens further confirmed this result and showed that the major source of CDK5 was endothelial cells. Depletion of CDK5 inhibited apoptosis of AECs, while the expression of CDK5 promoted apoptosis of AECs.
Conclusions: CDK5 induces apoptosis of AECs to promote AD. CDK5 appears to be a promising novel target for preventing AD.
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| http://dx.doi.org/10.21037/atm-22-3777 | DOI Listing |
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