Paradoxical Changes: EMMPRIN Tissue and Plasma Levels in Marfan Syndrome-Related Thoracic Aortic Aneurysms

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  • Alexander, Kyle C.
    • Affiliation: School of Medicine, Department of Surgery
  • Anderson, Carlton W.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Agala, Chris B.
    • Affiliation: School of Medicine, Department of Surgery
  • Tasoudis, Panagiotis
    • Affiliation: School of Medicine, Department of Surgery
  • Collins, Elizabeth N.
    • Affiliation: School of Medicine, Department of Surgery
  • Ding, Yiwen
    • Affiliation: School of Medicine, Department of Surgery
  • Blackwell, John W.
    • Affiliation: School of Medicine, Department of Surgery
  • Willcox, Danielle E.
    • Affiliation: School of Medicine, Department of Surgery
  • Farivar, Behzad S.
    • Other Affiliation: University of Virginia
  • Kibbe, Melina R.
    • Other Affiliation: University of Virginia
  • Ikonomidis, John S.
    • Affiliation: School of Medicine, Department of Surgery
  • Akerman, Adam W.
    • Affiliation: School of Medicine, Department of Surgery
Abstract
  • Background: Thoracic aortic aneurysms (TAAs) associated with Marfan syndrome (MFS) are unique in that extracellular matrix metalloproteinase inducer (EMMPRIN) levels do not behave the way they do in other cardiovascular pathologies. EMMPRIN is shed into the circulation through the secretion of extracellular vesicles. This has been demonstrated to be dependent upon the Membrane Type-1 MMP (MT1-MMP). We investigated this relationship in MFS TAA tissue and plasma to discern why unique profiles may exist. Methods: Protein targets were measured in aortic tissue and plasma from MFS patients with TAAs and were compared to healthy controls. The abundance and location of MT1-MMP was modified in aortic fibroblasts and secreted EMMPRIN was measured in conditioned culture media. Results: EMMPRIN levels were elevated in MFS TAA tissue but reduced in plasma, compared to the controls. Tissue EMMPRIN elevation did not induce MMP-3, MMP-8, or TIMP-1 expression, while MT1-MMP and TIMP-2 were elevated. MMP-2 and MMP-9 were reduced in TAA tissue but increased in plasma. In aortic fibroblasts, EMMPRIN secretion required the internalization of MT1-MMP. Conclusions: In MFS, impaired EMMPRIN secretion likely contributes to higher tissue levels, influenced by MT1-MMP cellular localization. Low EMMPRIN levels, in conjunction with other MMP analytes, distinguished MFS TAAs from controls, suggesting diagnostic potential.
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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Journal of Clinical Medicine
Journal volume
  • 13
Journal issue
  • 6
Page start
  • 1548
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  • English
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  • 2077-0383
Publisher
  • Multidisciplinary Digital Publishing Institute (MDPI)

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