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Review
. 2021 Dec;26(1):45-52.
doi: 10.1080/13510002.2021.1899473.

Oxidative stress in genetically triggered thoracic aortic aneurysm: role in pathogenesis and therapeutic opportunities

Stefanie S Portelli  1 , Brett D Hambly  1 , Richmond W Jeremy  2 , Elizabeth N Robertson  1   2
Affiliations
Review

Oxidative stress in genetically triggered thoracic aortic aneurysm: role in pathogenesis and therapeutic opportunities

Stefanie S Portelli et al. Redox Rep. 2021 Dec.

Abstract

Background: The primary objective of this review was to explore the contribution of oxidative stress to the pathogenesis of genetically-triggered thoracic aortic aneurysm (TAA). Genetically-triggered TAAs manifest substantial variability in onset, progression, and risk of aortic dissection, posing a significant clinical management challenge. There is a need for non-invasive biomarkers that predict the natural course of TAA and therapeutics that prevent aneurysm progression.Methods: An online systematic search was conducted within PubMed, MEDLINE, Scopus and ScienceDirect databases using keywords including: oxidative stress, ROS, nitrosative stress, genetically triggered thoracic aortic aneurysm, aortic dilatation, aortic dissection, Marfan syndrome, Bicuspid Aortic Valve, familial TAAD, Loeys Dietz syndrome, and Ehlers Danlos syndrome.Results: There is extensive evidence of oxidative stress and ROS imbalance in genetically triggered TAA. Sources of ROS imbalance are variable but include dysregulation of redox mediators leading to either insufficient ROS removal or increased ROS production. Therapeutic exploitation of redox mediators is being explored in other cardiovascular conditions, with potential application to TAA warranting further investigation.Conclusion: Oxidative stress occurs in genetically triggered TAA, but the precise contribution of ROS to pathogenesis remains incompletely understood. Further research is required to define causative pathological relationships in order to develop therapeutic options.

Keywords: Bicuspid Aortic Valve; Marfan syndrome; ROS; Thoracic aortic aneurysm; aortic dilatation; aortic dissection; oxidative stress; redox.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Unanswered questions concerning the role of oxidative stress in genetically triggered TAA pathogenesis. The relationship between oxidative stress and TAA development is likely due to altered aortic biomechanics, specifically due to intrinsic deficiencies in the aortic wall as in MFS, LDS, vEDS and fTAAD, or elevated wall stresses from turbulent flow as in BAV. Each render the aorta unable to adapt and instead undergo pathological remodelling leading to aneurysm formation. The specific contributions of redox pathway mediators to both oxidative stress and TAA pathogenesis are unknown. Therapeutics that can restore redox homeostasis may present a novel strategy to halt or reverse TAA development. MFS, Marfan syndrome; Loeys-Dietz syndrome; vEDS, vascular Ehlers Danlos syndrome; fTAAD, familial thoracic aortic aneurysm and dissection; BAV, bicuspid aortic valve; MMP, matrix metalloproteinase; SMCNL, smooth muscle cell nuclei loss; ECM, extracellular matrix.
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