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Review
. 2020 Mar 1;318(3):H652-H670.
doi: 10.1152/ajpheart.00621.2019. Epub 2020 Feb 21.

Pathogenic mechanisms and the potential of drug therapies for aortic aneurysm

Bo Liu  1 , David J Granville  2 , Jonathan Golledge  3 , Zamaneh Kassiri  4
Affiliations
Review

Pathogenic mechanisms and the potential of drug therapies for aortic aneurysm

Bo Liu et al. Am J Physiol Heart Circ Physiol. .

Abstract

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 ∼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.

Keywords: aortic aneurysm; aortic remodeling; proteases; smooth muscle cells.

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Conflict of interest statement

J. Golledge has received funds to consult Amgen and Reven and travel expenses to speak at international and national meetings. D. J. Granville is a cofounder and serves as a consultant/chief scientific officer for viDA Therapeutics. B. Liu. and Z. Kassiri have no conflicts of interest, financial or otherwise, to declare.

Figures

Fig. 1.
Fig. 1.
Aortic aneurysm can form in different regions along the aorta. Generally, if aneurysm is detected above the diaphragm it is referred to as thoracic aortic aneurysm (TAA), and if below the diaphragm it is referred to as abdominal aortic aneurysm (AAA).
Fig. 2.
Fig. 2.
Aortic aneurysm can present different morphologies, depending on the type of damage or remodeling in the aortic wall: saccular (A), fusiform (B), false aneurysm (C), and dissecting aneurysm (D).
Fig. 3.
Fig. 3.
A summary of the risk factors and cellular and molecular events that lead to aortic aneurysm. Although there are distinct differences between thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), these 2 pathologies also share common mechanisms. ECM, extracellular matrix; Gzms, granzymes; LDS, Loeys-Dietz syndrome; MMP, matrix metalloproteinases; SMC, smooth muscle cells; TGFβ1, transforming growth factor-β1.
See this image and copyright information in PMC

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