Salah A. Mohamed
UKSH-Campus Luebeck, Germany
Title: Genetic basis, pathogenesis, and haemodynamic aneurysm of the ascending aorta in patients with a bicuspid aortic valve
Biography
Biography: Salah A. Mohamed
Abstract
Statement of the Problem: The normal diameter of the aorta in adults is approximately 35 mm. A vessel bulge (aneurysm) is defined as permanent and exceeding of the standard value involving all layers of the vessel wall. Aneurysm of the ascending aorta is responsible for 1–2% of all deaths in industrialized countries. In approximately 50% of patients with a bicuspid aortic valve (BAV), the most common congenital heart disease, aneurysms of any or all segments of the aorta occurs. While aortic aneurysms are generally a benign condition, a consistent increase in the diameter of an aneurysm can give rise to catastrophic events such as acute aortic dissection (AAD) or aortic rupture. Methodology & Research orientation: Comprehensive genetic, molecular analysis and proteomic approaches to understand complex cellular processes and networks in the pathophysiology of aneurysms of the ascending aorta. To support two known kinds of hypotheses proposed to explain the causality in aneurysms formation, intrinsic factor is further investigated and analyzed in sense of vascular remodeling between congenital BAV and Marfan’s patients (MFS). In MFS, mutations in the gene encoding for the extracellular matrix protein fibrillin-1 can be observed; this mutations lead to dysregulation of the transforming growth factor-beta signaling. Findings: The interaction between mechanical forces and biological function is intimately coupled. In the subsequent molecular investigations of AAD, further genes were described, and their proteins were altered in patients with AAD. Conclusion & Significance: The etiology of BAV and the thoracic aortic aneurysm appears to be multiple. At the onset of valvulogenesis a number of mechanisms [e.g. Genes, epigenetic factors, fluid forces (Fig)] may be involved, either alone or combined, in the pathogenesis.
Fig. Genetic basis and pathogenesis of BAV/BAV associated aortopathy
1. Navarrete Santos et al., (2016). Collagen analysis of the ascending aortic dilatation associated with bicuspid aortic valve disease compared with tricuspid aortic valve. Arch Physiol Biochem. 2016;5:1-6
2. Lazar-Karsten et al., (2016). Generation and Characterization of Vascular Smooth Muscle Cell Lines Derived from a Patient with a Bicuspid Aortic Valve.
3. Paloschi et al., (2015). Aneurysm Development in Patients With a Bicuspid Aortic Valve Is Not Associated With Transforming Growth Factor-ß Activation. ATVBAHA 2015
4. Mohamed et al., (2006). Novel missense mutations (Thr595Met and Pro1795His) in NOTCH1 in patients with bicuspid aortic valve. BBRC. 2006;345:1460-146
5. Mohamed et al., (2005). Ubiquitin fusion degradation 1-like gene dysregulation in Bicuspid Aortic Valve. J Thorac Cardiovas Sur; 2005;130:1531-1536