Abstract

Background: Ribosome biogenesis is related to cell proliferation and contractility. Aortic smooth muscle cells showed proliferation and apoptosis in aortic dissection. Theoretically, ribosome biogenesis should be enhanced in aortic smooth muscle cell at proliferative state but suppressed at apoptosis state. It still needs to elucidate the ribosome biogenesis status and possible mechanism in aortic dissection. Methods: The BOP1 level, indicator of rRNA processing, was detected in clinical aortic samples. The protein synthesis, motility, apoptosis and related protein were investigated upon knockdown BOP1 expression, over-express BOP1 or cx-5461 treatment. PFTI± was used to deplete p53 function. BAPN-base mouse AD model was to explore the ribosome biogenesis status in vivo. Administration mouse with cx-5461 was used to interference ribosome biogenesis in vivo. P53(-/-) mice were used to explore the function of p53 in BAPN-base AD model. Findings: BOP1 was decreased in aortic sample of AD group. Knockdown BOP1 slowed-down protein synthesis rate and cell mobility in HASMCs. cx-5461 lead HASMCs apoptosis, which partly attenuated by depletion p53. Moreover, cx-5461 aggravated the severity of AD in vivo. cx-5461 cause proliferative- suppression and apoptosis in aortic smooth muscle cells. P53(-/-) mice showed extended life-span and lower AD incidence rate with significant increased proliferation and low apoptosis rate of aortic smooth muscle cells. Conclusion: Our finding indicated impaired ribosome biogenesis in aortic smooth muscle cells, results in p53 dependent proliferative-inhibition and apoptosis is involved in aortic dissection. Clinical Trial Registry Number: ChiCTR1800014384 Funding Statement: National Natural Science Foundation of China (NSFC)81570428; National Natural Science Foundation of China (NSFC)81600367. Conflicts of Interest: There were no potential conflicts of interest to be disclosed. Ethics Approval Statement: This study protocol was approved by the Clinical Research Ethics Committees of Renmin Hospital of Wuhan University of China and registered at the Chinese Clinical Trial Registry (ChiCTR), and informed written consent was obtained from each subject.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.