Inherited Thoracic Aortic Disease: New Insights and Translational Targets

Circulation. 2020 May 12;141(19):1570-1587. doi: 10.1161/CIRCULATIONAHA.119.043756. Epub 2020 May 11.

Abstract

Inherited thoracic aortopathies denote a group of congenital conditions that predispose to disease of the thoracic aorta. Aortic wall weakness and abnormal aortic hemodynamic profiles predispose these patients to dilatation of the thoracic aorta, which is generally silent but can precipitate aortic dissection or rupture with devastating and often fatal consequences. Current strategies to assess the future risk of aortic dissection or rupture are based primarily on monitoring aortic diameter. However, diameter alone is a poor predictor of risk, with many patients experiencing dissection or rupture below current intervention thresholds. Developing tools that improve the risk assessment of those with aortopathy is internationally regarded as a research priority. A robust understanding of the molecular pathways that lead to aortic wall weakness is required to identify biomarkers and therapeutic targets that could improve patient management. Here, we summarize the current understanding of the genetically determined mechanisms underlying inherited aortopathies and critically appraise the available blood biomarkers, imaging techniques, and therapeutic targets that have shown promise for improving the management of patients with these important and potentially fatal conditions.

Keywords: Marfan syndrome; aneurysm, dissecting; aortic aneurysm; bicuspid aortic valve; biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aorta, Thoracic* / metabolism
  • Aorta, Thoracic* / pathology
  • Aorta, Thoracic* / physiopathology
  • Aorta, Thoracic* / surgery
  • Aortic Aneurysm, Thoracic / diagnostic imaging
  • Aortic Aneurysm, Thoracic / genetics*
  • Aortic Aneurysm, Thoracic / physiopathology
  • Aortic Aneurysm, Thoracic / therapy
  • Aortic Dissection / diagnostic imaging
  • Aortic Dissection / genetics*
  • Aortic Dissection / physiopathology
  • Aortic Dissection / therapy
  • Aortic Rupture / diagnostic imaging
  • Aortic Rupture / genetics*
  • Aortic Rupture / physiopathology
  • Aortic Rupture / therapy
  • Biomarkers / metabolism
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Targeted Therapy
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Signal Transduction
  • Translational Research, Biomedical
  • Vascular Surgical Procedures

Substances

  • Biomarkers