Genetic determinants of aortic aneurysm pathogenesis

Genetic determinants of aortic aneurysm pathogenesis

T.I. Khomyakova^1,2, V.A. Mkhitarov¹, Yu.N. Khomyakov², O.V. Makarova¹

Tatyana I. Khomyakova, e-mail: tatkhom@yandex.ru

¹Petrovsky National Research Centre of Surgery, Moscow, Russian Federation

²Synergy University, Moscow, Russian Federation

Aortic aneurysm (AA) represents a progressive dilatation of any aortic segment, generally arising from the interplay of multiple precipitating factors in genetically susceptible individuals. Characterization of the underlying genetic architecture holds promise for elucidating the pathogenetic mechanisms and signaling cascades implicated in AA initiation and progression, as well as for the discovery of candidate diagnostic biomarkers and druggable targets to advance pharmacotherapy in affected patients. The present review provides a comprehensive analysis of contemporary evidence pertaining to the genetic foundations of both thoracic and abdominal aortic aneurysm formation. While high-penetrance risk genes have been more thoroughly delineated and are more robustly associated with thoracic aortic disease, emerging research methodologies are uncovering a unique genetic landscape underlying abdominal aortic aneurysms.

Genetic predisposition to aneurysm development is conferred by both common polymorphisms, whose allele frequencies in aneurysm patient populations deviate from those in control cohorts by no more than 5%, and rare pathogenic mutations affecting genes encoding extracellular matrix constituents and signaling pathway components. The convergence of gene-level investigations (genomics), global RNA expression analysis (transcriptomics), heritable modifications of the genetic material (epigenomics), and comprehensive protein profiling (proteomics) with clinical phenotypic data will ultimately enable the adoption of personalized approaches to screening, longitudinal monitoring, and potentially pharmacological prophylaxis of this life-threatening condition.

Keywords: narrative review, aortic aneurysm, thoracic aortic aneurysm, abdominal aortic aneurysm, smooth muscle cells, extracellular matrix, metalloproteinases, genetic predisposition.

For citation: Khomyakova T.I., Mkhitarov V.A., Khomyakov Yu.N., Makarova O.V. Genetic determinants of aortic aneurysm pathogenesis. RMJ. 2026;5:27–31. DOI: 10.32364/2225-2282-2026-5-5