Aortas reveal the myth of male privilege

Abstract

The commonest congenital heart defect in adults is the bicuspid aortic valve. It affects 1.3 % of the population worldwide and is responsible for more deaths and complications than all the other congenital heart defects combined (Fig. 1). Fusion of aortic valve leaflets occurs most commonly (≈80 %) between the right coronary and left coronary leaflets (RL), which are the anterior leaflets of the aortic valve. Fusion also occurs between the right coronary and noncoronary leaflets (RN; ≈17 %), and least commonly between the noncoronary and left coronary leaflets (LN; ≈2 %). Verma and Siu recently provided an overview of the basic principles, recent advances, and recommendations for the treatment of adults with bicuspid aortopathy [1]. Aortic stenosis and insufficiency are the hallmarks of a bicuspid aortic valve; however, dilatation of any or all proximal aortic segments extending from the aortic root to the aortic arch, namely, bicuspid aortopathy, is also present in at least half of affected persons (Fig. 2). A heterogeneous pattern of aortic dilatation develops in an affected person, probably reflecting heterogeneity in molecular, rheologic, and clinical features [2].In this issue, Lee et al. [3] suggest that aortic remodeling in patients with bicuspid aortic valve-associated thoracic aneurysms is sex-dependent. They studied the structural remodeling in patients with bicuspid aortic valves and compared molecular alterations in men and women by investigating aortic aneurysmal tissue samples. Women had smaller aortic aneurysms than men, but the size difference disappeared when the data were normalized for body surface area. Elastin fibers were disorganized and reduced in men and women. However, only men exhibited disarrayed collagen fibers and reduced protein. The mRNA levels were similar in both groups, suggesting post-translational degradation of proteins, more prominent in men compared to women. The enzymatic elastase activity was elevated in both men and women, while the membrane-anchored collagenase membrane type 1 matrix metalloprotease (MT1-MMP) was more increased in men than in women. Furthermore, matrix metalloprotease (MMP)-8 and MMP-13 were lower, while MMP-2 was higher in women than men. Tissue-inhibitor of metalloprotease (TIMP)-3 and TIMP-4 were similarly decreased in both sexes, while TIMP-2 was increased in women. The vascular smooth muscle cell density in the media of dilated aortas from men corresponded to an increase in caspase-3 cleavage, compared to women. The authors suggest a sex-dependent MMP/TIMP axis, including collagen remodeling and vascular smooth muscle cell survival, could protect women from aortic rupture.Lee et al. [3] claim that sex-related effects have not been explored in thoracic aortic aneurysms associated with bicuspid aortic valve disease. Predictors of bicuspid aortopathy progression include older age, male sex, elevated systolic blood pressure, coexisting aortic valve stenosis or regurgitation, and morphologic features of the valve, namely, right or left cusp fusion [4]....