Studies on Aortic and Aortic Valve Diseases | Abstract
Clinical & Experimental Cardiology

Clinical & Experimental Cardiology
Open Access

ISSN: 2155-9880


Studies on Aortic and Aortic Valve Diseases

Salah A. Mohamed, Johnson J Yan and Hans H Sievers

Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, with an estimated incidence of 1%–2% in the general population. Patients with BAV are predisposed to early and frequent stenosis, regurgitation, and endocarditis, often accompanied by aneurysm and dissection. A family-based genome-wide analysis found that BAV was linked to chromosomal regions 5q, 13q, and 18q, with autosomal dominant inheritance, reduced penetrance and a non-Mendelian inheritance pattern. Mutations in the transmembrane receptor-encoding gene NOTCH1 have been detected in familial and sporadic BAV cases. Mutations in the vascular smooth muscle cell alpha actin gene (ACTA2) have also been identified in BAV patients. Expression of UFD1L, a gene that is highly expressed in the outflow tract during embryogenesis, was downregulated in the cusps of BAV patients compared with those of controls. BAV is associated with left ventricular outflow tract abnormality, including aortic coarctation, arch hypoplasia, and supravalvular and mitral valve stenosis. A male predominance of more than 3:1 has been reported for BAV. This anomaly is very frequent in X0 Turner’s syndrome. Many studies have observed similarities between the histology of aortic aneurysmal tissue in the connective tissue disorder Marfan syndrome (MFS) and the histology of the corresponding tissue in BAV. In this lecture, we review our present understanding of BAV malformation and ascending thoracic aortic aneurysm pathogenesis. We discuss the genetic basis and the basic pathology underlying BAV and aortopathy and compare these with known mechanisms underlying MFS.