Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice
Kip P, Sluiter TJ, MacArthur MR, Tao M, Kruit N, Mitchell SJ, Jung J, Kooijman S, Gorham J, Seidman JG, Quax PHA, Decano JL, Aikawa M, Ozaki CK, Mitchell JR and de Vries MR
Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice
Kip P, Sluiter TJ, MacArthur MR, Tao M, Kruit N, Mitchell SJ, Jung J, Kooijman S, Gorham J, Seidman JG, Quax PHA, Decano JL, Aikawa M, Ozaki CK, Mitchell JR and de Vries MR
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.
Short-term Pre-operative Methionine Restriction Induces Browning of Perivascular Adipose Tissue and Improves Vein Graft Remodeling in Mice
Kip P, Sluiter TJ, MacArthur MR, Tao M, Jung J, Mitchell SJ, Kooijman S, Kruit N, Gorham J, Seidman JG, Quax PHA, Aikawa M, Ozaki CK, Mitchell JR and de Vries MR
Short-term Pre-operative Methionine Restriction Induces Browning of Perivascular Adipose Tissue and Improves Vein Graft Remodeling in Mice
Kip P, Sluiter TJ, MacArthur MR, Tao M, Jung J, Mitchell SJ, Kooijman S, Kruit N, Gorham J, Seidman JG, Quax PHA, Aikawa M, Ozaki CK, Mitchell JR and de Vries MR
Short-term preoperative methionine restriction (MetR) shows promise as a translatable strategy to modulate the body's response to surgical injury. Its application, however, to improve post-interventional vascular remodeling remains underexplored. Here, we find that MetR protects from arterial intimal hyperplasia in a focal stenosis model and adverse vascular remodeling after vein graft surgery. RNA sequencing reveals that MetR enhances the brown adipose tissue phenotype in arterial perivascular adipose tissue (PVAT) and induces it in venous PVAT. Specifically, PPAR-α was highly upregulated in PVAT-adipocytes. Furthermore, MetR dampens the post-operative pro-inflammatory response to surgery in PVAT-macrophages and . This study shows for the first time that the detrimental effects of dysfunctional PVAT on vascular remodeling can be reversed by MetR, and identifies pathways involved in browning of PVAT. Furthermore, we demonstrate the potential of short-term pre-operative MetR as a simple intervention to ameliorate vascular remodeling after vascular surgery.
Tc17 CD8+ T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development
van Duijn J, de Jong MJM, Benne N, Leboux RJT, van Ooijen ME, Kruit N, Foks AC, Jiskoot W, Bot I, Kuiper J and Slütter B
Tc17 CD8+ T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development
van Duijn J, de Jong MJM, Benne N, Leboux RJT, van Ooijen ME, Kruit N, Foks AC, Jiskoot W, Bot I, Kuiper J and Slütter B
CD8+ T cells can differentiate into subpopulations that are characterized by a specific cytokine profile, such as the Tc17 population that produces interleukin-17. The role of this CD8+ T-cell subset in atherosclerosis remains elusive. In this study, we therefore investigated the contribution of Tc17 cells to the development of atherosclerosis.
