Aortic aneurysms account for 1-2% of deaths in Western countries, and despite improvements in surgical repair, morbidity and mortality remain high, especially with thoracic aortic aneurysms and dissections (TAAD). Degeneration of the medial layer of the aorta leads to aortic dilation and/or rupture; pathological changes in the media include progressive elastin fiber fragmentation, loss of smooth muscle cells, and proteoglycan accumulation. Mutations causing hereditary TAAD affect proteins regulating transforming growth factor-β signaling (e.g., Loeys-Dietz syndrome and Marfan syndrome), or components of the smooth muscle cell contractile apparatus. Aortic pathology has been attributed to smooth muscle cell phenotypic alterations and activation of stress pathways, leading to increased production of tissue-destructive matrix metalloproteinases and increased oxidative stress. Abdominal aortic aneurysms (AAAs) may share with TAAD some of these pathogenic mechanisms. While blood pressure control with β-adrenergic or angiotensin receptor blockers modestly improve the prognosis of patients with TAAD, there is no treatment to prevent the pathologic changes in the aorta.
Researchers at UC San Diego have used a newly developed, potent antioxidant in mouse studies of TAAD to show that it completely prevented age-related development of aortic media degeneration and aortic dilation.
The therapeutic could potentially be used to prevent and treat a variety of aortic diseases associated with excess oxidative stress, including TAAD and AAA.
This is at the experimental state.
The technology is patent pending and available for licensing or collaborations.
Aortic aneurysms, aortic disease, Marfan syndrome, oxidative stress, antioxidant