Colchicine Alleviates Non-Atherosclerotic Vascular Aging by Targeting Endothelial Dysfunction and Inflammatory Status

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Soroush Mohammadi Jouabadi,1,2 Annika A Jüttner,1 Keivan Golshiri,1 Ehsan Ataei Ataabadi,1 Martine de Boer,3 Rene De Vries,1 Richard Van Veghel,1 Yoëlle Goos,1 Youri Boon,1 Usha Musterd-Bhaggoe,1 Dirk J Duncker,3 Antoinette MaassenVanDenBrink,1 AH Jan Danser,1 Willem A Bax,4 Jan H Cornel,5,6 Anton JM Roks1 1Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; 2Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; 3Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; 4Department of Internal Medicine, Northwest Clinics, Alkmaar, the Netherlands; 5Department of Cardiology, Radboud University Nijmegen Medical Centre, the Netherlands; 6Department of Cardiology, Northwest Clinics, Alkmaar, the NetherlandsCorrespondence: Anton JM Roks, Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands, Email a.roks@erasmusmc.nlBackground: Non-atherosclerotic vascular aging (NAVA) contributes to cardiovascular risk through progressive arterial stiffening and endothelial dysfunction. Colchicine, best known for anti-inflammatory activity, has been proposed to protect vascular structure and function. We evaluated whether chronic colchicine mitigates NAVA in a smooth-muscle–specific ERCC1 knockout (SMC-KO) mouse model of DNA-damage–driven vascular aging.Methods: We performed experiments in the SMC-KO treated with colchicine (0.1mg/kg/day) or vehicle from the age of 10 to 22 weeks. Endothelial function was assessed by acetylcholine-induced vasorelaxation, and vascular structure by pulse-wave velocity (PWV), carotid intima–media thickness (cIMT), and elastin integrity.Results: SMC-KO mice developed increased arterial stiffness and impaired acetylcholine-mediated relaxation. Chronic colchicine significantly (p< 0.01) lowered PWV, preserved elastin architecture, and improved endothelium-dependent relaxation, while sodium-nitroprusside responses and systemic cytokine levels remained unchanged.Conclusion: Chronic colchicine treatment preserves endothelial function and vascular elastin structure and reduces arterial stiffness in a DNA-damage–driven model of non-atherosclerotic vascular aging. These findings highlight colchicine’s pleiotropic vascular benefits beyond anti-inflammation, supporting its potential repurposing for primary prevention in vascular aging and cardiovascular health or the development of colchicine-mimicking drugs with greater selectivity and improved safety profiles. Keywords: vascular aging, colchicine, stiffness, endothelial function, beta-adrenoreceptors

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