Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3774_Библиотеки_им_академика_М_И_Перельмана

should already be considered for aortic diameters as small as 4.0–4.5cm.

Aortic aneurysms result from structural weakening of the aortic wall [1], and pre­dispose to aortic rupture and dissection because of a progressive increase in wall tension. Only 5% of patients experience warning symptoms prior to aortic rupture

TAAs, located above the diaphragm, occur less frequently than AAAs but have been more extensively investigated due to a higher heritability and a younger age at onset. In approximately 20% of TAA patients, a positive family history is identied and in about 30% of these, a mutation is found in one of the roughly 30 currently known TAA genes (Table13.1). Patients with thoracic aortic aneurysm and dissec­tion (TAAD) often do not present with other risk factors such as hypertension.

Aortic aneurysms are pathological dilatations of the aorta, caused by vascular wall weakness. The aortic wall consists of three different layers: the intima, the media and the adventitia. The innermost layer, i.e. the intima, is composed of a metaboli­cally important endothelial monolayer that is supported by internal elastic laminae. This sub-endothelial elastic matrix harmonizes the motion of the intima and media during cyclic aortic expansion or contraction [10, 11]. The media makes up the larg­est part of the vessel wall and consists of vascular smooth muscle cells (VSMCs) embedded in extracellular matrix (ECM) proteins such as elastins, collagens and proteoglycans. The ECM provides elasticity and tensile strength, besides sequester­ing a variety of growth factors. ECM homeostasis is controlled by matrix metallo­proteinases (MMPs) and tissue inhibitors of MMPs (TIMPS) produced by synthetic VSMCs during vascular remodelling. Whereas MMPs degrade the ECM, TIMPs reduce ECM degradation through MMP inhibition [12]. Contractile VSMCs control the vessel’s luminal diameter, and hence blood pressure, by mediating vessel con­traction or relaxation. The adventitia is the outer layer of the vessel wall and consists of collagen and elastin bres as well as broblasts, immunomodulatory cells, vasa vasorum endothelial cells and pericytes. It contributes to aortic integrity and pro­vides nutritional circulation to the vascular wall [10, 11].

In TAA patients, a shift from contractile VSMCs towards synthetic VSMCs has been observed leading to an imbalance between MMP and TIMP expression. Pathological amounts of MMPs are secreted, resulting in disproportionate ECM degradation [13], ECM disorganisation and growth factor release [14]. Moreover, loss of VSMC contractility reduces the aortic wall’s capacity to properly control the luminal diameter. In addition to a shift in VSMC function, excessive VSMC apopto­sis (see Glossary) is typically observed. In the VSMC-depleted regions, degradation products of proteoglycans and glycosaminoglycans as well as inammatory cells can be found [15, 16]. Collectively, these events are hallmarks of a phenomenon called medial degeneration, which weakens the aortic wall and contributes to aortic aneurysm formation and progression according to Laplace’s Law: circumferential wall tension=transmural pressure x vessel radius. Ruptures or dissections occur when the mechanical stress on the vascular wall overpowers the tissue strength [17].