Focal Induction of Reactive Oxygen Species as a Trigger of an Aortic Valve Degeneration

Background: Many different and interacting factors are involved in the process of degenerative aortic valve disease. Current animal models regarding the aspect of reactive oxygen species (ROS) focus on its systemic effects. We developed an animal model that allows a detailed analysis of the isolated and local effects of ROS in the pathophysiology of the degenerative aortic valve disease.

Methods: We applied a photodynamic reaction as source of ROS to the aortic valve by inserting a laser-fiber via the carotid artery of male rats, aiming a laser (1 mW; 652 nm) at the aortic valve for 60 min after administration of a photosensitizer (meta-tetrahydroxyphenylchlorine) 24 h before. Next to these animals (ROS), control- and sham-groups (n = 7, each) for every observation period (t = 0 d; t = 8 d; t = 84 d; t = 164 d) were established. The amount of ROS-generation, morphological changes, inflammatory-, immune- and apoptotic reactions and hemodynamic changes of the aortic valves were assessed by appropriate histology, immunohistology and chemistry as well as echocardiography.

Results: The ROS-group displayed a significantly increased amount of ROS (p < 0.01) after the photodynamic reaction, as well as a significantly increased inflammatory activation of the endothelium (p < 0.05) at t = 0 d. However, the integrity of the endothelium itself was not compromised and no signs of apoptosis were observed. No signs of morphological changes of the valves were observed in the early postinterventional period (t = 0 d, t = 8 d). In the ROS-group, the leaflets of the aortic valves were significantly calcified (p < 0.05) as well as the transvalvular gradient was significantly increased (p < 0.01) at t = 168 d.

Conclusion: We could demonstrate the feasibility to establish a photodynamic reaction in a small animal model. Any direct physical or chemical short-term effects of the laser or photosensitizer could be excluded. Obviously, the amount of generated ROS was sufficient to induce signaling pathways that end up in morphological and functional aspects of an aortic valve degeneration. We provided a small animal model that could serve as platform to analyze the isolated role of ROS or in combination with other factors in the context of the degenerative aortic valve disease.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
13 February 2024