Update in Biomolecular and Genetic Bases of Bicuspid Aortopathy

Abstract

Bicuspid aortic valve (BAV) associated with aortopathy is the most common congenital heart disease in the general population. Far from being a simple harmless valve malformation, it can be a complex and heterogeneous disease and a source of chronic and acute pathology (early valvular disease, aneurysm, dissection). In the previous years, intense research has been carried out to find out and understand its mechanisms, but the pathophysiology of the disease is still not fully understood and many questions remain open. Recent studies have discovered several genetic mutations involved in the development of valvular and aortic malformations, but still cannot explain more than 5-10% of cases. Other studies have also focused on molecular alterations and cellular processes (TGF-β pathway, microRNAs, degradation of the extracellular matrix, metalloproteinases, etc.), being a field in constant search and development, looking for a therapeutic target to prevent the development of the disease. Increased knowledge about this multifaceted disorder, derived from both basic and clinical research, may influence the diagnosis, follow-up, prognosis, and therapies of affected patients in the near future. This review focuses on the latest and outstanding developments on the molecular and genetic investigations of the bicuspid aortopathy.

Keywords: aortopathy; bicuspid aortic valve; bicuspid aortopathy; biomarkers; congenital heart disease; genetics.

Figure 1

Bicuspid aortopathy is a double road. The congenital defect can develop in the person who suffers from both valvulopathy (stenosis or regurgitation) and aortopathy (aneurysms and risk of spontaneous dissection). On the left, echocardiographic image of BAV (arrow). On the right, a resonance image of dilated ascending aorta (marked straight line).

Figure 2

Imaging of bicuspid associated aneurysm. (A) The 2D image of a transthoracic echocardiogram in the parasternal long axis plane showing the dilated aorta (Ao) marked with the straight line (LV: left ventricle). (B) Computed tomography (CT) in axial plane showing the very dilated ascending aorta (Ao) at the level of the sinuses of Valsalva. (C) The 3D CT reconstruction, showing a huge 8 cm aneurysm.

Figure 3

Bicuspid aortopathy is a complex syndrome that includes many parts. Translational research is essential, from the laboratory to daily medical practice, in order to address not only each piece (etiology, diagnostic methods, complications, and treatment) but also the whole problem. In this way, each step that improves scientific knowledge in bicuspid aortopathy improves the lives of the patients who suffer from it. TTE: transthoracic echocardiography; CT: computed tomography; TEE: transesophageal echocardiography; CMR: cardiac magnetic resonance.