Background: Aortic aneurysms (AAs), characterized by localized dilation of the aorta, represent a life-threatening condition often progressing asymptomatically until rupture. This review explores the multifactorial pathogenesis of aortic wall degeneration, integrating molecular, cellular, and structural perspectives. Methods: A focused search of international bibliographic sources was conducted using WoS, PubMed, and Scopus databases, Google Scholar was used as an additional source. The aim was to facilitate the analytical integration of studies that highlight the relationship between pathological features and molecular pathways involved in AA development and progression. Results: The review synthesizes findings from 78 studies spanning diverse disciplines, emphasizing the dynamic interplay between genetic predispositions and environmental factors in aneurysm development. Key pathological mechanisms include extracellular matrix (ECM) degradation mediated by upregulated matrix metalloproteinases (MMPs), chronic inflammation with immune cell infiltration, vascular smooth muscle cell (VSMC) apoptosis and phenotypic switching, oxidative stress, and dysregulated transforming growth factor-beta (TGF-β) signaling. Emerging roles of ADAM/ADAMTS proteases, non-coding RNAs, and epigenetic modifications are highlighted, alongside novel contributions from intraluminal thrombus (ILT) and perivascular adipose tissue (PVAT), which foster hypoxia and inflammation. Conclusions: Understanding these interwoven mechanisms is crucial for the development of effective diagnostic tools and personalized treatments aimed at halting aneurysm progression and rupture.
Aortic Wall Degeneration in Aortic Aneurysms. Pathological and Molecular Insights
Costa, Davide;Andreucci, Michele;Bracale, Umberto Marcello;Serra, Raffaele
2026-01-01
Abstract
Background: Aortic aneurysms (AAs), characterized by localized dilation of the aorta, represent a life-threatening condition often progressing asymptomatically until rupture. This review explores the multifactorial pathogenesis of aortic wall degeneration, integrating molecular, cellular, and structural perspectives. Methods: A focused search of international bibliographic sources was conducted using WoS, PubMed, and Scopus databases, Google Scholar was used as an additional source. The aim was to facilitate the analytical integration of studies that highlight the relationship between pathological features and molecular pathways involved in AA development and progression. Results: The review synthesizes findings from 78 studies spanning diverse disciplines, emphasizing the dynamic interplay between genetic predispositions and environmental factors in aneurysm development. Key pathological mechanisms include extracellular matrix (ECM) degradation mediated by upregulated matrix metalloproteinases (MMPs), chronic inflammation with immune cell infiltration, vascular smooth muscle cell (VSMC) apoptosis and phenotypic switching, oxidative stress, and dysregulated transforming growth factor-beta (TGF-β) signaling. Emerging roles of ADAM/ADAMTS proteases, non-coding RNAs, and epigenetic modifications are highlighted, alongside novel contributions from intraluminal thrombus (ILT) and perivascular adipose tissue (PVAT), which foster hypoxia and inflammation. Conclusions: Understanding these interwoven mechanisms is crucial for the development of effective diagnostic tools and personalized treatments aimed at halting aneurysm progression and rupture.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
