Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome
Summary: Myxomatous valve disease (MVD) can lead to cardiac dysfunction and heart failure, yet medical therapies are lacking. C-C chemokine receptor type 2 (CCR2)+ immune cell infiltration promotes mitral valve inflammation in a Marfan syndrome (MFS) mouse model. The CCR2 genetic knockout reduces in...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | JACC: Basic to Translational Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452302X22002182 |
| _version_ | 1798018856010121216 |
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| author | Na Xu, PhD Katherine E. Yutzey, PhD |
| author_facet | Na Xu, PhD Katherine E. Yutzey, PhD |
| author_sort | Na Xu, PhD |
| collection | DOAJ |
| description | Summary: Myxomatous valve disease (MVD) can lead to cardiac dysfunction and heart failure, yet medical therapies are lacking. C-C chemokine receptor type 2 (CCR2)+ immune cell infiltration promotes mitral valve inflammation in a Marfan syndrome (MFS) mouse model. The CCR2 genetic knockout reduces inflammation with downregulated proteases and improved extracellular matrix integrity. Pharmacological inhibition of CCR2+ cell infiltration by RS504393 prevents the initiation and progression of MVD, indicated by restored protease expression, improved extracellular matrix organization, and reduced valve leaflet thickness in MFS mice. Thus, the CCR2 antagonist RS504393 is a promising therapy for the treatment of MVD in MFS. |
| first_indexed | 2024-04-11T16:31:08Z |
| format | Article |
| id | doaj.art-200fccab3fc04348ad0de065e4c4a7ee |
| institution | Directory Open Access Journal |
| issn | 2452-302X |
| language | English |
| last_indexed | 2024-04-11T16:31:08Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JACC: Basic to Translational Science |
| spelling | doaj.art-200fccab3fc04348ad0de065e4c4a7ee2022-12-22T04:14:00ZengElsevierJACC: Basic to Translational Science2452-302X2022-11-0171111431157Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan SyndromeNa Xu, PhD0Katherine E. Yutzey, PhD1Division of Molecular Cardiovascular Biology, the Heart Institute, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USAAddress for correspondence: Dr Katherine E. Yutzey, Molecular Cardiovascular Biology, ML7020, Cincinnati Children’s Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039, USA.; Division of Molecular Cardiovascular Biology, the Heart Institute, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USASummary: Myxomatous valve disease (MVD) can lead to cardiac dysfunction and heart failure, yet medical therapies are lacking. C-C chemokine receptor type 2 (CCR2)+ immune cell infiltration promotes mitral valve inflammation in a Marfan syndrome (MFS) mouse model. The CCR2 genetic knockout reduces inflammation with downregulated proteases and improved extracellular matrix integrity. Pharmacological inhibition of CCR2+ cell infiltration by RS504393 prevents the initiation and progression of MVD, indicated by restored protease expression, improved extracellular matrix organization, and reduced valve leaflet thickness in MFS mice. Thus, the CCR2 antagonist RS504393 is a promising therapy for the treatment of MVD in MFS.http://www.sciencedirect.com/science/article/pii/S2452302X22002182C-C chemokine receptor type 2extracellular matrixinflammationmyxomatous valve disease |
| spellingShingle | Na Xu, PhD Katherine E. Yutzey, PhD Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome JACC: Basic to Translational Science C-C chemokine receptor type 2 extracellular matrix inflammation myxomatous valve disease |
| title | Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome |
| title_full | Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome |
| title_fullStr | Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome |
| title_full_unstemmed | Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome |
| title_short | Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome |
| title_sort | therapeutic ccr2 blockade prevents inflammation and alleviates myxomatous valve disease in marfan syndrome |
| topic | C-C chemokine receptor type 2 extracellular matrix inflammation myxomatous valve disease |
| url | http://www.sciencedirect.com/science/article/pii/S2452302X22002182 |
| work_keys_str_mv | AT naxuphd therapeuticccr2blockadepreventsinflammationandalleviatesmyxomatousvalvediseaseinmarfansyndrome AT katherineeyutzeyphd therapeuticccr2blockadepreventsinflammationandalleviatesmyxomatousvalvediseaseinmarfansyndrome |