Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases

Huakang Zhou; Dilaware Khan; Sajid Muhammad Hussain; Norbert Gerdes; Carsten Hagenbeck; Majeed Rana; Jan Frederick Cornelius; Sajjad Muhammad

doi:10.1186/s12950-023-00366-7

Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases

J Inflamm (Lond). 2023 Nov 24;20(1):41. doi: 10.1186/s12950-023-00366-7.

Authors

Huakang Zhou¹, Dilaware Khan², Sajid Muhammad Hussain³, Norbert Gerdes^{4

5}, Carsten Hagenbeck⁶, Majeed Rana⁷, Jan Frederick Cornelius¹, Sajjad Muhammad^{1

8

9}

Affiliations

¹ Department of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine- Universität Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
² Department of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine- Universität Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany. [email protected].
³ Cologne Center for Genomics (CCG), University of Cologne, Weyertal 115b, 50931, Cologne, Germany.
⁴ Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
⁵ Cardiovascular Reasearch Institute Düsseldorf (CARID), Medical Faculty, Heinrich-Heine- University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
⁶ Clinic for Gynecology and Obstetrics, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225, Düsseldorf, Germany.
⁷ Department of Oral-, Maxillofacial and Facial Plastic Surgery, University Hospital Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
⁸ Department of Neurosurgery, University Hospital Helsinki, Topeliuksenkatu 5, Helsinki, 00260, Finland.
⁹ Department of Neurosurgery, King Edward Medical University, Lahore, Pakistan.

Abstract

Background: Smoking, alcohol abuse, and hypertension are - among others, potential risk factors for cardiovascular diseases. These risk factors generate oxidative stress and cause oxidative stress-induced DNA damage, resulting in cellular senescence and senescence-associated secretory phenotype (SASP). The SASP factors in feed-forward response exacerbate inflammation and cause tissue remodeling, resulting in atherosclerotic plaque formation and rupture.

Results: Colchicine inhibited ROS generation and mitigated oxidative stress-induced DNA damage. It dampened oxidative stress-induced endothelial cell senescence and improved the expression of DNA repair protein KU80 and aging marker Lamin B1. The drug attenuated the expression of senescence marker P21 at mRNA and protein levels. The pathway analysis showed that colchicine inhibited NF-κB and MAPKs pathways and subdued mTOR activation. Colchicine also attenuated mRNA expression of interleukin (IL)-1β, IL-6, IL-8, MCP-1, ICAM-1, and E-selectin. Furthermore, colchicine reduced the mRNA and protein expression of matrix metalloproteinase (MMP-2).

Conclusion: In summary, colchicine blocked oxidative stress-induced senescence and SASP by inhibiting the activation of NF-κB and MAPKs pathways.

Keywords: Cellular senescence; Colchicine; Endothelial cells; Inflammation; MAPKs; NFκ-B; Oxidative stress; mTOR.