Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 318, Issue 3, Pages H652-H670Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00621.2019
Keywords
aortic aneurysm; aortic remodeling; proteases; smooth muscle cells
Funding
- National Heart, Lung, and Blood Institute [R01-HL-088447, R01-HL-122562]
- National Health and Medical Research Council
- Townsville Hospital and Health Services Study, the Education and Research Trust Fund
- Queensland Government
- National Heart Foundation
- James Cook University
- Queensland Government, Australia
- Canadian Institutes for Health Research and Michael Smith Foundation for Health Research
- Canadian Institute for Health Research, Heart and Stroke Foundation
- Canada Foundation for Innovation
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Aortic aneurysm is a permanent focal dilation of the aorta. It is usually an asymptomatic disease but can lead to sudden death due to aortic rupture. Aortic aneurysm-related mortalities are estimated at similar to 200,000 deaths per year worldwide. Because no pharmacological treatment has been found to be effective so far, surgical repair remains the only treatment for aortic aneurysm. Aortic aneurysm results from changes in the aortic wall structure due to loss of smooth muscle cells and degradation of the extracellular matrix and can form in different regions of the aorta. Research over the past decade has identified novel contributors to aneurysm formation and progression. The present review provides an overview of cellular and noncellular factors as well as enzymes that process extracellular matrix and regulate cellular functions (e.g., matrix metalloproteinases, granzymes, and cathepsins) in the context of aneurysm pathogenesis. An update of clinical trials focusing on therapeutic strategies to slow abdominal aortic aneurysm growth and efforts underway to develop effective pharmacological treatments is also provided.
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