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Review
. 2019 Dec 19;51(12):1-15.
doi: 10.1038/s12276-019-0286-3.

Extracellular Matrix, Regional Heterogeneity of the Aorta, and Aortic Aneurysm

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Free PMC article
Review

Extracellular Matrix, Regional Heterogeneity of the Aorta, and Aortic Aneurysm

Sayantan Jana et al. Exp Mol Med. .
Free PMC article

Abstract

Aortic aneurysm is an asymptomatic disease with dire outcomes if undiagnosed. Aortic aneurysm rupture is a significant cause of death worldwide. To date, surgical repair or endovascular repair (EVAR) is the only effective treatment for aortic aneurysm, as no pharmacological treatment has been found effective. Aortic aneurysm, a focal dilation of the aorta, can be formed in the thoracic (TAA) or the abdominal (AAA) region; however, our understanding as to what determines the site of aneurysm formation remains quite limited. The extracellular matrix (ECM) is the noncellular component of the aortic wall, that in addition to providing structural support, regulates bioavailability of an array of growth factors and cytokines, thereby influencing cell function and behavior that ultimately determine physiological or pathological remodeling of the aortic wall. Here, we provide an overview of the ECM proteins that have been reported to be involved in aortic aneurysm formation in humans or animal models, and the experimental models for TAA and AAA and the link to ECM manipulations. We also provide a comparative analysis, where data available, between TAA and AAA, and how aberrant ECM proteolysis versus disrupted synthesis may determine the site of aneurysm formation.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Cross section of the aortic wall and its remodeling during physiological versus pathological remodeling. The tunica media is separated from the tunica intima by the internal elastic lamina, and from the tunica adventitia by the external elastic lamina. Intermittent layers of elastic fiber and smooth muscle cells make up the tunica media, while this region is also rich in proteoglycans and glycoproteins. During physiological remodeling, degradation of ECM proteins by MMPs (and other proteases) is balanced by newly synthesized ECM proteins, while tissue inhibitors of proteases (TIMPs) keep the proteolytic activity of MMPs under check. Excess ECM degradation, or impaired ECM renewal synthesis, along with smooth muscle cell death, lead to adverse ECM remodeling as observed in aortic aneurysm

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