Aortic Pathologies and Connective Tissue Disorders

Aortic pathologies encompass a spectrum of structural abnormalities of the aorta, the main arterial conduit from the heart, including aneurysmal dilatation, dissection and rupture. These conditions are often compounded by inherited connective tissue disorders such as Marfan syndrome, Loeys-Dietz syndrome and vascular Ehlers-Danlos syndrome, in which mutations disrupt key components of the extracellular matrix and perturb transforming growth factor-β (TGF-β) signalling. The resultant weakness of the aortic wall and dysfunction of vascular smooth muscle cells predispose to progressive dilatation and catastrophic tear. Advances in molecular genetics, imaging and biomechanical characterisation have deepened understanding of pathological mechanisms, enabling risk stratification, targeted surveillance and development of novel therapeutic strategies. Despite regional variations in prevalence and access to care, these disorders pose a global challenge owing to their high morbidity and mortality when diagnosis or intervention is delayed. Clinical management now integrates genotype-guided thresholds for prophylactic surgery, personalised pharmacotherapy to modulate TGF-β and angiotensin pathways, and consensus-driven guidelines for imaging intervals and lifestyle modification.

Research from Nature Portfolio

One foundational study has identified a convergent epigenetic mechanism underlying thoracic aortic aneurysm in both TGF-β signalling–deficient and cytoskeletal-mutant backgrounds. Investigators demonstrated that mutations affecting TGF-β receptors or vascular smooth muscle contractile proteins promote formation of a ternary complex of HDAC9, BRG1 and the long noncoding RNA MALAT1. This complex binds to chromatin and represses expression of contractile apparatus genes through histone H3 lysine 27 trimethylation. Genetic or pharmacological disruption of MALAT1 or HDAC9 restores contractile gene expression, improves aortic wall architecture and halts experimental aneurysm progression, highlighting an epigenetic axis amenable to therapeutic targeting.

Aortic Pathologies and Connective Tissue Disorders publication trend

The graph below shows the total number of articles in aortic pathologies and connective tissue disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Aortic aneurysm: Localised enlargement of the aorta due to weakening of the vessel wall.

Aortic dissection: A tear in the intimal layer of the aorta allowing blood to split its wall layers.

Extracellular matrix: The network of proteins (e.g. fibrillin, collagen) that provides structural support and regulates cell behaviour.

Transforming growth factor-β signalling: A cellular pathway controlling extracellular matrix synthesis and vascular cell phenotype; dysregulation is central to connective tissue disorders.

Vascular smooth muscle cell: The contractile cells in the medial layer of the artery responsible for maintaining vessel tone and structure.

References

1. Management of aortic disease in children with FBN1-related Marfan syndrome. European Heart Journal (2024).
2. The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-β signalling. Cardiovascular Research (2024).
3. An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm. Nature Communications (2018).