Palmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling.

Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE

Original Publication: [London] : Nature Pub. Group

Diabetes Mellitus, Type 2*/metabolism ; Plaque, Atherosclerotic*/metabolism; Animals ; Humans ; Mice ; Apolipoproteins E/metabolism ; Disease Models, Animal ; Macrophages/metabolism ; Mice, Knockout ; Myocytes, Smooth Muscle/metabolism ; Palmitic Acid/metabolism

Patients with Type 2 Diabetes Mellitus are increasingly susceptible to atherosclerotic plaque vulnerability, leading to severe cardiovascular events. In this study, we demonstrate that elevated serum levels of palmitic acid, a type of saturated fatty acid, are significantly linked to this enhanced vulnerability in patients with Type 2 Diabetes Mellitus. Through a combination of human cohort studies and animal models, our research identifies a key mechanistic pathway: palmitic acid induces macrophage Delta-like ligand 4 signaling, which in turn triggers senescence in vascular smooth muscle cells. This process is critical for plaque instability due to reduced collagen synthesis and deposition. Importantly, our findings reveal that macrophage-specific knockout of Delta-like ligand 4 in atherosclerotic mice leads to reduced plaque burden and improved stability, highlighting the potential of targeting this pathway. These insights offer a promising direction for developing therapeutic strategies to mitigate cardiovascular risks in patients with Type 2 Diabetes Mellitus.
(© 2024. The Author(s).)

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0 (Apolipoproteins E)
2V16EO95H1 (Palmitic Acid)
0 (DLL4 protein, human)
0 (DLL4 protein, mouse)

Date Created: 20240212 Date Completed: 20240217 Latest Revision: 20240217

20240217

PMC10861578

10.1038/s41467-024-45582-8

38346959