Genetic and molecular mechanisms of hereditary thoracic aortic aneurysm and dissection (Review)

Thoracic aortic aneurysm and dissection (TAAD) is a life‑threatening disease with an insidious onset and a largely elusive pathogenesis. Hereditary TAAD (HTAD) can be classified into syndromic forms, including Marfan syndrome, Loeys‑Dietz syndrome and vascular Ehlers‑Danlos syndrome and non‑syndromic forms, including familial TAAD and bicuspid aortic valve‑associated TAAD. Current evidence suggests that HTAD development shares several core mechanisms, including extracellular matrix disruption, dysregulated transforming growth factor‑β signaling, vascular smooth muscle cell dysfunction and, in the case of bicuspid aortic valve, abnormal hemodynamic stress. The present review summarizes the major genes and molecular pathways involved in HTAD and discusses their contributions to disease progression. Elucidating the underlying mechanisms associated with HTAD may facilitate risk assessment and the development of targeted therapies.