Affiliation:
1. Department of Biomedical Engineering, Yale University, New Haven, Connecticut
2. Vascular Biology and Therapeutics Program, Yale University, New Haven, Connecticut
3. Department of Surgery, Yale University, New Haven, Connecticut
Abstract
Thoracic aortopathy, especially aneurysm, dissection, and rupture, is responsible for significant morbidity and mortality. Uncontrolled hypertension and aging are primary risk factors for such conditions, and they contribute to an increase in the mechanical stress on the wall and an increase in its structural vulnerability, respectively. Select genetic mutations also predispose to these lethal conditions, and the collection of known mutations suggests that dysfunctional mechanosensing and mechanoregulation of the extracellular matrix may contribute to pathogenesis and disease progression. In the absence of a well-accepted pharmacotherapy, nonsurgical treatments tend to focus on reducing the mechanical loading on the aorta, particularly via the use of antihypertensive medications and recommendations to avoid strenuous exercises such as weight lifting. In this brief review, we discuss the important effects of central artery stiffening on global hemodynamics and, in particular, on the increase in pulse pressure that acts on the proximal thoracic aorta. We consider Marfan syndrome as an illustrative aortopathy but discuss other conditions leading to thoracic aortic aneurysm and dissection. We highlight the importance of phenotyping the aorta biomechanically, not just clinically, and emphasize the utility of mouse models in elucidating molecular and mechanical mechanisms of disease. Notwithstanding the widely recognized role of central artery stiffening in driving end-organ disease, we suggest that there is similarly a need to consider its key role in thoracic aortopathy.
Funder
HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)
HHS | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
44 articles.
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