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Pathophysiology of Aortic Aneurysms: Insights from Animal Studies.

ABSTRACT: Aortic aneurysms are defined as dilations of the aorta greater than 50 percent. Currently, the only effective treatment for aortic aneurysms is surgical repair, which is recommended only to those that meet criteria. There is no available pharmaceutical therapy to slow aneurysm growth and thus prevent lethal rupture. The development of a number of murine models has allowed in depth studies of various cellular and extracellular components of aneurysm pathophysiology. The identification of key therapeutic targets has resulted in several clinical trials evaluating pharmaceutical candidates to treat aneurysm progression. In this review, we focus on providing recent updates on developments in murine models of aortic aneurysm. In addition, we discuss recent studies of the various cellular and extracellular components of the aorta along with the abutting aortic structures that contribute to aneurysm development and progression.

SUBMITTER: Khoury MK

PROVIDER: S-EPMC7508467 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Pathophysiology of Aortic Aneurysms: Insights from Animal Studies.

Khoury Mitri K MK Stranz Amelia R AR Liu Bo B

Cardiology and cardiovascular medicine 20200831 4

Aortic aneurysms are defined as dilations of the aorta greater than 50 percent. Currently, the only effective treatment for aortic aneurysms is surgical repair, which is recommended only to those that meet criteria. There is no available pharmaceutical therapy to slow aneurysm growth and thus prevent lethal rupture. The development of a number of murine models has allowed in depth studies of various cellular and extracellular components of aneurysm pathophysiology. The identification of key ther ...[more]

PMID: 32968712

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Project description:ObjectiveThe need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress.MethodsSerum and aortic tissue from n = 24 patients and serum from n = 19 healthy controls was analyzed by ELISA and gelatin zymography. 24 patients had ascending aortic aneurysms, 10 of them also had aortic root aneurysms. Three patients had normally functioning valves, 12 had regurgitation alone, eight had regurgitation and stenosis and one had only stenosis. Patients had bicuspid and tricuspid aortic valves (9/15). Serum samples were taken preoperatively, and the aortic wall specimen collected during surgical aortic repair.ResultsPro-MMP-2 was identified in all serum and tissue samples. Pro-MMP-2 was detected in all tissue and serum samples from patients with ascending aortic/aortic root aneurysms, irrespective of valve morphology or other clinical parameters and in serum from healthy controls. We also identified active MMP-2 in all tissue samples from patients with ascending aortic/aortic root aneurysms. None of the analyzed serum samples revealed signals relatable to active MMP-2. No correlation between aortic tissue total MMP-2 or tissue pro-MMP-2 or tissue active MMP-2 and serum MMP-2 was found and tissue MMP-2/pro-MMP-2/active MMP-2 did not correlate with aortic diameter. This evidence shows that pro-MMP-2 is the predominant MMP-2 species in serum of patients and healthy individuals and in aneurysmatic aortic tissue, irrespective of aortic valve configuration. Active MMP-2 species are either not released into systemic circulation or not detectable in serum. There is no reliable connection between aortic tissue-and serum MMP-2 isoforms, nor any indication that pro-MMP-2 functions as a common marker of high aortic wall stress.

Dataset Information

Pathophysiology of Aortic Aneurysms: Insights from Animal Studies.

Publications

Pathophysiology of Aortic Aneurysms: Insights from Animal Studies.

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