MG 53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling. J Am Heart Assoc 2019 Feb 19;8(4):e009960
Date
02/12/2019Pubmed ID
30741589Pubmed Central ID
PMC6405656DOI
10.1161/JAHA.118.009960Scopus ID
2-s2.0-85061251064 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
Author List
Adesanya TMA, Russell M, Park KH, Zhou X, Sermersheim MA, Gumpper K, Koenig SN, Tan T, Whitson BA, Janssen PML, Lincoln J, Zhu H, Ma JAuthor
Joy Lincoln PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAortic Valve
Aortic Valve Stenosis
Biomarkers
Blotting, Western
Calcinosis
Cells, Cultured
Disease Models, Animal
Echocardiography
Humans
Immunohistochemistry
Male
Mice
Signal Transduction
Stress, Mechanical
Swine
Tripartite Motif Proteins
Ventricular Remodeling
