MG 53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling
Background The aortic valve of the heart experiences constant mechanical stress under physiological conditions. Maladaptive valve injury responses contribute to the development of valvular heart disease. Here, we test the hypothesis that MG 53 (mitsugumin 53), an essential cell membrane repair protein, can protect valvular cells from injury and fibrocalcific remodeling processes associated with valvular heart disease. Methods and Results We found that MG 53 is expressed in pig and human patient aortic valves and observed aortic valve disease in aged Mg53-/- mice. Aortic valves of Mg53-/- mice showed compromised cell membrane integrity. In vitro studies demonstrated that recombinant human MG 53 protein protects primary valve interstitial cells from mechanical injury and that, in addition to mediating membrane repair, recombinant human MG 53 can enter valve interstitial cells and suppress transforming growth factor-β-dependent activation of fibrocalcific signaling. Conclusions Together, our data characterize valve interstitial cell membrane repair as a novel mechanism of protection against valvular remodeling and assess potential in vivo roles of MG 53 in preventing valvular heart disease.
| Errataetall: |
ErratumIn: J Am Heart Assoc. 2020 Jun 16;9(12):e014526. - PMID 32539606 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Journal of the American Heart Association - 8(2019), 4 vom: 19. Feb., Seite e009960 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Adesanya, T M Ayodele [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.03.2020 Date Revised 09.12.2022 published: Print ErratumIn: J Am Heart Assoc. 2020 Jun 16;9(12):e014526. - PMID 32539606 Citation Status MEDLINE |
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| doi: |
10.1161/JAHA.118.009960 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM293674477 |
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| 100 | 1 | |a Adesanya, T M Ayodele |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a MG 53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling |
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| 500 | |a published: Print | ||
| 500 | |a ErratumIn: J Am Heart Assoc. 2020 Jun 16;9(12):e014526. - PMID 32539606 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background The aortic valve of the heart experiences constant mechanical stress under physiological conditions. Maladaptive valve injury responses contribute to the development of valvular heart disease. Here, we test the hypothesis that MG 53 (mitsugumin 53), an essential cell membrane repair protein, can protect valvular cells from injury and fibrocalcific remodeling processes associated with valvular heart disease. Methods and Results We found that MG 53 is expressed in pig and human patient aortic valves and observed aortic valve disease in aged Mg53-/- mice. Aortic valves of Mg53-/- mice showed compromised cell membrane integrity. In vitro studies demonstrated that recombinant human MG 53 protein protects primary valve interstitial cells from mechanical injury and that, in addition to mediating membrane repair, recombinant human MG 53 can enter valve interstitial cells and suppress transforming growth factor-β-dependent activation of fibrocalcific signaling. Conclusions Together, our data characterize valve interstitial cell membrane repair as a novel mechanism of protection against valvular remodeling and assess potential in vivo roles of MG 53 in preventing valvular heart disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cell membrane repair | |
| 650 | 4 | |a fibrosis | |
| 650 | 4 | |a heart valve | |
| 650 | 4 | |a transforming growth factor‐β | |
| 650 | 4 | |a valvular heart disease | |
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| 700 | 1 | |a Russell, Melanie |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Ki Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Sermersheim, Matthew A |e verfasserin |4 aut | |
| 700 | 1 | |a Gumpper, Kristyn |e verfasserin |4 aut | |
| 700 | 1 | |a Koenig, Sara N |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Whitson, Bryan A |e verfasserin |4 aut | |
| 700 | 1 | |a Janssen, Paul M L |e verfasserin |4 aut | |
| 700 | 1 | |a Lincoln, Joy |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jianjie |e verfasserin |4 aut | |
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