Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice
Abstract Short-term preoperative methionine restriction (MetR) is a promising translatable strategy to mitigate surgical injury response. However, its application to improve post-interventional vascular remodeling remains underexplored. Here we find that MetR protects from arterial intimal hyperplas...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53844-8 |
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| author | Peter Kip Thijs J. Sluiter Michael R. MacArthur Ming Tao Nicky Kruit Sarah J. Mitchell Jonathan Jung Sander Kooijman Josh Gorham Jonathan G. Seidman Paul H. A. Quax Julius L. Decano Masanori Aikawa C. Keith Ozaki James R. Mitchell Margreet R. de Vries |
| author_facet | Peter Kip Thijs J. Sluiter Michael R. MacArthur Ming Tao Nicky Kruit Sarah J. Mitchell Jonathan Jung Sander Kooijman Josh Gorham Jonathan G. Seidman Paul H. A. Quax Julius L. Decano Masanori Aikawa C. Keith Ozaki James R. Mitchell Margreet R. de Vries |
| author_sort | Peter Kip |
| collection | DOAJ |
| description | Abstract Short-term preoperative methionine restriction (MetR) is a promising translatable strategy to mitigate surgical injury response. However, its application to improve post-interventional vascular remodeling remains underexplored. Here we find that MetR protects from arterial intimal hyperplasia in a focal stenosis model and pathologic vascular remodeling following vein graft surgery in male mice. RNA sequencing reveals that MetR enhances browning in arterial (thoracic aorta) perivascular adipose tissue (PVAT) and induces it in venous (caval vein) PVAT. Specifically, Ppara is highly upregulated in PVAT-adipocytes upon MetR. Furthermore, MetR dampens the postoperative pro-inflammatory response to surgery in PVAT-macrophages in vivo and in vitro. This study shows that the detrimental effects of dysfunctional PVAT on vascular remodeling can be reversed by MetR, and identifies pathways involved in MetR-induced browning of PVAT. Furthermore, we demonstrate the potential of short-term preoperative MetR as a simple intervention to ameliorate vascular remodeling after vascular surgery. |
| format | Article |
| id | doaj-art-8f299f54c6294dc69d98482c052be4d7 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8f299f54c6294dc69d98482c052be4d72025-08-20T02:49:59ZengNature PortfolioNature Communications2041-17232024-11-0115111910.1038/s41467-024-53844-8Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male micePeter Kip0Thijs J. Sluiter1Michael R. MacArthur2Ming Tao3Nicky Kruit4Sarah J. Mitchell5Jonathan Jung6Sander Kooijman7Josh Gorham8Jonathan G. Seidman9Paul H. A. Quax10Julius L. Decano11Masanori Aikawa12C. Keith Ozaki13James R. Mitchell14Margreet R. de Vries15Department of Surgery, Brigham & Women’s Hospital, Harvard Medical SchoolDepartment of Surgery, Brigham & Women’s Hospital, Harvard Medical SchoolDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public HealthDepartment of Surgery, Brigham & Women’s Hospital, Harvard Medical SchoolEinthoven Laboratory for Experimental Vascular Medicine and Regenerative Medicine, Leiden University Medical CenterLudwig Princeton Branch, Ludwig Institute for Cancer Research, Princeton UniversityDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public HealthDivision of Endocrinology, Department of Medicine, Leiden University Medical CenterDepartment of Genetics, Harvard Medical SchoolDepartment of Genetics, Harvard Medical SchoolEinthoven Laboratory for Experimental Vascular Medicine and Regenerative Medicine, Leiden University Medical CenterCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Harvard Medical SchoolCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Harvard Medical SchoolDepartment of Surgery, Brigham & Women’s Hospital, Harvard Medical SchoolDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public HealthDepartment of Surgery, Brigham & Women’s Hospital, Harvard Medical SchoolAbstract Short-term preoperative methionine restriction (MetR) is a promising translatable strategy to mitigate surgical injury response. However, its application to improve post-interventional vascular remodeling remains underexplored. Here we find that MetR protects from arterial intimal hyperplasia in a focal stenosis model and pathologic vascular remodeling following vein graft surgery in male mice. RNA sequencing reveals that MetR enhances browning in arterial (thoracic aorta) perivascular adipose tissue (PVAT) and induces it in venous (caval vein) PVAT. Specifically, Ppara is highly upregulated in PVAT-adipocytes upon MetR. Furthermore, MetR dampens the postoperative pro-inflammatory response to surgery in PVAT-macrophages in vivo and in vitro. This study shows that the detrimental effects of dysfunctional PVAT on vascular remodeling can be reversed by MetR, and identifies pathways involved in MetR-induced browning of PVAT. Furthermore, we demonstrate the potential of short-term preoperative MetR as a simple intervention to ameliorate vascular remodeling after vascular surgery.https://doi.org/10.1038/s41467-024-53844-8 |
| spellingShingle | Peter Kip Thijs J. Sluiter Michael R. MacArthur Ming Tao Nicky Kruit Sarah J. Mitchell Jonathan Jung Sander Kooijman Josh Gorham Jonathan G. Seidman Paul H. A. Quax Julius L. Decano Masanori Aikawa C. Keith Ozaki James R. Mitchell Margreet R. de Vries Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice Nature Communications |
| title | Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice |
| title_full | Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice |
| title_fullStr | Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice |
| title_full_unstemmed | Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice |
| title_short | Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice |
| title_sort | preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice |
| url | https://doi.org/10.1038/s41467-024-53844-8 |
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