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

Author:

Wang Xiqiang,Zhu Ling,Liu Jing,Ma Yanpeng,Qiu ChuanORCID,Liu Chengfeng,Gong Yangchao,Yuwen Ya,Guan Gongchang,Zhang Yong,Pan ShuoORCID,Wang JunkuiORCID,Liu ZhongweiORCID

Abstract

AbstractPatients 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.

Publisher

Springer Science and Business Media LLC

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