Unveiling the protective role of ESM1 in endothelial cell proliferation and lipid reprogramming.

May 05, 2025

Experts: Yukun Li,Anbo Gao,Wenchao Zhou,Xing Tang,Tian Zeng,Tingyu Fan,Weimin Jiang,Min Tang,Fan Ouyang

Palmitic acid (PA), being the most prevalent free fatty acid in the human, holds significant implications as a risk factor for atherosclerosis (AS) due to its ability to induce physiological dysfunction in endothelial cells (ECs). Endothelial cell-specific molecule 1 (ESM1), has been identified as a marker for activated ECs. Nevertheless, the mechanisms underlying ESM1-induced endothelial cell proliferation remain elusive. The expression of ESM1, ANGPTL4 and autophagy related protein were confirmed by western blot. Proliferation ability was tested by MTT and EdU. Lipids level was confirmed by Oil red staining. Autophagic flux was confirmed by Monodansylcadaverine (MDC) staining and pCMV-mCherry-GFP-LC3B fluorescence staining assay. The mouse model of AS was used to observe the effect of PA on the ESM1-ANGPTL4-autophagy signaling axis. This study elucidates ESM1-ANGPTL4 axis in maintaining proliferation of ECs and lipid reprogramming. Furthermore, it has been observed that PA has the ability to stimulate EC to autonomously increase the expression of ESM1, which in turn can counteract the detrimental effects of PA on ECs. Conversely, when ESM1 is suppressed, the damaging effects of PA on ECs are exacerbated. Mechanistically, our findings indicate that ESM1 facilitates EC proliferation and lipids homeostasis by up-regulating autophagy through ANGPTL4. This effect of ESM1 on ECs can be attenuated by ATG7 inhibiting. Additionally, the serum levels of ESM1 were found to be elevated in AS mice. ESM1 was found to enhance ECs proliferation and mitigate endothelial cell injury induced by PA through the upregulation of autophagy. This mechanism potentially serves as a protective factor against atherosclerosis progression.
© 2025. The Author(s).

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ABOUT THE EXPERTS

Yukun Li,Anbo Gao,Wenchao Zhou,Xing Tang,Tian Zeng,Tingyu Fan,Weimin Jiang,Min Tang,Fan Ouyang

Yukun Li

Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.

Anbo Gao

Department of Cardiology, Xiangya Hospital Zhuzhou, Zhuzhou Central Hospital, Central South University, Central South University, Zhuzhou, Hunan, China.

Clinical Research Institute, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Wenchao Zhou

Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.

Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Xing Tang

Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.

Tian Zeng

Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.

Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Tingyu Fan

Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.

Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Weimin Jiang

Department of Cardiology, Xiangya Hospital Zhuzhou, Zhuzhou Central Hospital, Central South University, Central South University, Zhuzhou, Hunan, China.

Min Tang

Department of Cardio-Thoracic Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Fan Ouyang

Department of Cardiology, Xiangya Hospital Zhuzhou, Zhuzhou Central Hospital, Central South University, Central South University, Zhuzhou, Hunan, China. 9304117@csu.edu.cn.

Department of Cardiology, Zhuzhou Hospital, the Affiliated Hospital of Xiangya Medical College of Central South University, Zhuzhou, Hunan, China. 9304117@csu.edu.cn.

Department of Cardiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. 9304117@csu.edu.cn.