Molecular Pathogenesis of Fibulin-4 Associated Aortic Aneurysms

markdownabstract__Abstract__ Aortic disease represents one of the major causes of morbidity and mortality in the industrialized society. Approximately 2% of all deaths are caused by aortic aneurysm and dissections [1]. Aneurysms are defined as a local widening of the artery with more than 50 percent of the normal diameter [2]. An aneurysm can result in a fatal aortic rupture or in an aortic dissection, which is a tear in the wall of the artery that causes blood to flow between the layers of the wall and forces the layers apart [3]. Dissections involving the ascending aorta, Stanford type A dissections, have a mortality rate of 1-2% per hour and should be immediately treated surgically [4], while dissections occurring in the descending aorta are usually treated medically and have an in-hospital mortality of about 10% [5]. However, an acute aortic dissection may also result in a rupture and with thoracic aortic rupture mortality is very high, approximately 94 to 100%. Both diseases have principles and techniques of surgical treatment in common. Surgery of aneurysms of the ascending aorta and arch, the descending aorta, and the thoracoabdominal aorta has been associated with a reduced operative mortality of respectively 2.9%, 3.0% and 11.9% between 1995 and 2004 [6]. However, the diagnosis of aneurysms and dissections is at the moment limited to computed tomography and echocardiography, usually in late and severe stages of the diseases. The main mechanisms by which these diseases occur are largely unknown. It is thought that aneurysm formation is the result of changes in the extracellular matrix (ECM) of the aortic wall and signaling pathways of the vasculature [3]. However, more insight into the molecular mechanisms leading to aneurysm formation is required in order to identify predisposing factors and new detection protocols for earlier detection of aortic aneurysms