Introduction

Each year in the United States, nearly 10,000 people die from aortic aneurysms, while over 16,000 people die from complications associated with aortic disease, making aneurysm disease the 18th most common cause of death in the United States, and the 15th most common cause of death in individuals older than 65 years.[1] An aortic aneurysm is defined as an enlargement of the aorta, the main artery that carries blood form the heart to the rest of the body, to a size 1.5 times its normal baseline diameter. Although aortic disease is more prevalent in men, the prognosis is typically worse in women, who with smaller aortic diameters, are more likely to have an aortic dissection, or experience aortic rupture.[2] The pathogenesis of TAA covers a wide range of idiopathic-degenerative, congenitally acquired, genetically based, and traumatically induced disorders of the aorta.[3] While it is likely that the degenerative process begins earlier in life, the mean age at diagnosis is approximately 65 years.[4] Given the predominantly asymptomatic nature of thoracic aortic disease development, the incidence can be difficult to estimate; however, previous reports have demonstrated that both the prevalence and incidence of thoracic aortic disease had doubled between 1982 and 2002.[5],[6],[7] With the aging of Baby Boomers, current population projections suggest that the number of individuals 65 years and older will double by the year 2030,[8] and when this is combined with improved awareness and advancements in noninvasive imaging, the number of patients diagnosed and living with thoracic aortic disease is likely to rise, and may be higher than originally expected.[9] Once diagnosed, a “watch and wait” surveillance program is initiated until the risk of aortic rupture outweighs the risk of the surgical repair. Autopsy studies have revealed that the most common cause of death is aortic rupture.[10],[11] In spite of the fact that the vast majority of patients with aortic rupture make it to the emergency department alive, 97% die within the first 6 hours after arrival. Recent advancements such as endovascular stent grafting have significantly decreased the early mortality and perioperative complications associated with open surgical procedures; however, endovascular repair is not without limitations, and in the long-term (after 4 years) has not proven to provide significant benefit over open surgical repair.[9] Importantly, neither option is aimed at treating the underlying cellular and molecular mechanisms responsible for aortic wall remodeling and dilatation. This highlights a critical need for a better understanding of the etiology of aortic disease and the development of better tools for diagnosis, prognosis, and treatment.

Since the first case of aortic aneurysm recorded by Antyllus in the 2nd century CE, through the rudimentary advancements of diagnosis by Vesalius in 1555, the first comprehensive text on the pathology of aneurysm by Lancisi in 1728, and a major advancement in the surgical management of aortic aneurysm disease by Mata in 1888, the words of William Osler (1849-1919) continue to ring true: “There is no disease more conducive to clinical humility than aneurysm of the aorta”.[12],[13] In this chapter, we will provide a comprehensive review of normal aortic structure and the pathophysiology of thoracic aortic disease, and will provide insights into some of the mechanisms involved in extracellular matrix (ECM) remodeling and how they can be leveraged for diagnostic and therapeutic use, as well as a discussion of strategies for advancing the field.