Neutralization of reactive oxygen species with cobinamide augments aortic dissections and rupture in BAPN-administered mice

Authors

• Alexis Richard, University of Texas Medical School at Houston
• Zhen Zhou, University of Texas Medical School at Houston
• Jose Emiliano Esparza Pinelo, University of Texas Medical School at Houston
• Callie S. Kwartler, University of Texas Medical School at Houston
• Hema Kalyanaraman, University of California San Diego Health
• Gerry R. Boss, University of California San Diego Health
• Hong S. Lu, University of KentuckyFollow
• Alan Daugherty, University of KentuckyFollow
• Dianna M. Milewicz, University of Texas Medical School at HoustonFollow

Abstract

Thoracic aortic aneurysms involving the root and ascending aorta progressively enlarge and can lead to life-threatening acute aortic dissections, collectively termed thoracic aortic disease (TAD). Oxidative stress due to an excess of reactive oxygen species (ROS) has been implicated in TAD pathogenesis by promoting vascular inflammation, extracellular matrix degradation, and smooth muscle cell apoptosis. Cobinamide (Cbi), a potent antioxidant and vitamin B12 analog, has been reported to slow aortic aneurysm growth in TAD mouse models. We evaluated its efficacy in mice administered b-aminopropionitrile (BAPN) to induce TAD, a model in which aneurysms progress to dissections. C57BL/6J mice of both sexes were administered either BAPN alone or BAPN plus Cbi in drinking water from postnatal day 21 (P21). Survival analysis showed that 56% of mice in the BAPN group died from aortic rupture by P49, whereas mortality increased to 91% in the BAPN þ Cbi group (P ¼ 0.049). Necropsy confirmed thoracic aortic rupture as the cause of death. At P35, proximal aortic analyses showed that Cbi significantly reduced ROS abundance in the ascending aorta, based on decreased dihydroethidium staining and lower oxidative stress markers, including protein carbonylation and DNA oxidation by 8-hydroxy-deoxyguanosine staining. Cbi did not affect aortic diameters by echocardiography or elastic fiber fragmentation. Cbi was associated with reduced oxidative stress in aortic tissue; it did not prevent aortic dissection and was associated with increased rupture-related mortality in the BAPN model. These findings highlight context-dependent roles of ROS in TAD and the importance of carefully evaluating antioxidant strategies in dissection-prone settings.

Document Type

Article

Publication Date

8-1-2026

Notes/Citation Information

Publisher Copyright: Copyright © 2026 The Authors.

Digital Object Identifier (DOI)

10.1152/ajpheart.00314.2026

Archival?

Archival

Repository Citation

Richard, Alexis; Zhou, Zhen; Esparza Pinelo, Jose Emiliano; Kwartler, Callie S.; Kalyanaraman, Hema; Boss, Gerry R.; Lu, Hong S.; Daugherty, Alan; and Milewicz, Dianna M., "Neutralization of reactive oxygen species with cobinamide augments aortic dissections and rupture in BAPN-administered mice" (2026). Physiology Faculty Publications. 201.
https://uknowledge.uky.edu/physiology_facpub/201