Medical Therapy of Aortic Aneurysms: A Pathophysiology-Based Approach

Abstract

One of the critical points in the pathogenesis of aortic aneurysms (AAs) is the disruption of the balance between vascular extracellular matrix (ECM) deposition and degradation. AAs are common features in some genetically determined diseases of the connective tissue, such as Marfan and Ehlers-Danlos. Acquired factors determining an enhanced inflammatory state of the arterial wall also play a key role. Previous studies have determined the role of tumor growth factor β (TGF-β); as a principal mediator of the pathogenesis of the alterations of the arterial wall homeostasis in AAs. The medical management of any AA is mainly focused on the use of pharmacological agents that reduce hemodynamic stress of the aortic wall, since hypertension is the major risk factor for the enlargement and rupture of the AAs. However, this is far from being a comprehensive pathophysiology-based therapeutic approach. Drugs potentially able to reduce the release of TGF-β may play a role in the pathogenesis of the AAs. They work by improving matrix repair, decreasing the proteolytic pattern and inhibition of angiotensin-converting enzyme (ACE) as well as preventing angiotensin II-induced angiotensin type-1 receptor (AT1R) activation. A new pathophysiology-based therapeutic approach, involving the mechanisms leading to the rupture of the AAs, could represent an additional tool in combination with the current established antihypertensive therapy.

Osteogenesis Imperfecta and Other Defects of Bone Development as Occasional Causes of Adult Osteoporosis

“…However, clinically, LDS exhibits a more aggressive course than MFS or the vascular type IV EDS, with higher morbidity and mortality due to the complications of arterial and aortic dissections [262]. The medical management of aneurysmal disease in MFS and LDS is mainly focused on the use of β-blocking agents that reduce hemodynamic stress of the aortic wall [263].…”