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  • Review Article
  • Published:

Aetiology and management of hereditary aortopathy

Nature Reviews Cardiology volume 14, pages 197–208 (2017)Cite this article

Subjects

Key Points

  • Aortic aneurysms are a major health problem accounting for 1–2% of all deaths in Western countries

  • The genetic basis of thoracic aortic aneurysms (TAAs) is highly heterogeneous

  • Dysregulated transforming growth factor-β signalling, extracellular matrix homeostasis, and vascular smooth muscle cell contraction are crucial disease mechanisms in TAA

  • Further elucidation of the genetic aetiology of TAA will advance patient management by improving family-based risk stratification, by paving the way for personalized treatment protocols and by pinpointing novel therapeutic targets

  • The pathological mechanisms of inherited TAA might serve as a paradigm for sporadic TAA

Abstract

Aortic aneurysms are a major health problem because they account for 1–2% of all deaths in the Western population. Although abdominal aortic aneurysms (AAAs) are more prevalent than thoracic aortic aneurysms (TAAs), TAAs have been more exhaustively studied over the past 2 decades because they have a higher heritability and affect younger individuals. Gene identification in both syndromic and nonsyndromic TAA is proceeding at a rapid pace and has already pinpointed >20 genes associated with familial TAA risk. Whereas these genes explain <30% of all cases of familial TAA, their functional characterization has substantially improved our knowledge of the underlying pathological mechanisms. As such, perturbed extracellular matrix homeostasis, transforming growth factor-β signalling, and vascular smooth muscle cell contractility have been proposed as important processes in TAA pathogenesis. These new insights enable novel treatment options that are currently being investigated in large clinical trials. Moreover, together with the advent of next-generation sequencing approaches, these genetic findings are promoting a shift in the management of patients with TAA by enabling gene-tailored interventions. In this Review, we comprehensively describe the molecular landscape of familial TAA, and we discuss whether familial TAA, from a biological point of view, can serve as a paradigm for the genetically more complex forms of the condition, such as sporadic TAA or AAA.

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Figure 1: Functional classification of genes associated with syndromic and nonsyndromic thoracic aortic aneurysms.
Figure 2: Signalling pathways involved in familial thoracic aortic aneurysms (TAA).

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Acknowledgements

B.L. receives research funding from the Fund for Scientific Research Flanders [G.0221.12]; the Foundation Leducq [12 CVD 03] and the European Research Council [ERC-StG-2012-30972]. B.L. is a senior clinical investigator of the Fund for Scientific Research Flanders (FWO). A.V. is a postdoctoral researcher supported by the Fund for Scientific Research Flanders (FWO). I.L. holds a PhD grant from the Agency for Innovation by Science and Technology (IWT).

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Authors and Affiliations

  1. Centre of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, Antwerp, 2650, Belgium

    Aline Verstraeten, Ilse Luyckx & Bart Loeys

  2. Department of Human Genetics, Radboud University Nijmegen Medical Center, Geert Grooteplein-Zuid 10, Nijmegen, 6525, Netherlands

    Bart Loeys

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  1. Aline Verstraeten
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All the authors researched data for the article, discussed its content, and wrote the manuscript. B.L. and A.V. reviewed and edited the article before submission.

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Correspondence to Bart Loeys.

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Verstraeten, A., Luyckx, I. & Loeys, B. Aetiology and management of hereditary aortopathy. Nat Rev Cardiol 14, 197–208 (2017). https://doi.org/10.1038/nrcardio.2016.211

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