Severe hypertriglyceridemia caused by Gpihbp1 deficiency facilitates vascular remodeling through increasing endothelial activation and oxidative stress.

Rui Fan, Xiangbo An, Yao Wang, Jinjin Zhang, Shuang Liu, Jie Bai, Jiatian Li, Qiuyue Lin, Yunpeng Xie, Yunlong Xia, Jiawei Liao

Biochimica et biophysica acta. Molecular and cell biology of lipids 2023 Jul

filter terms:

Hypertriglyceridemia (HTG) is an independent risk factor for atherosclerosis. However, its impact on non-atherosclerotic cardiovascular diseases remains largely unknown. Glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1 (GPIHBP1) is essential for the hydrolysis of circulating triglycerides and loss of functional GPIHBP1 causes severe HTG. In this study, we used Gpihbp1 knockout (GKO) mice to investigate the potential effects of HTG on non-atherosclerotic vascular remodeling. We compared the aortic morphology and gene expressions between three-month-old and ten-month-old GKO mice and their age-matched wild-type controls. We also conducted similar comparisons between GKO mice and wild-type controls in an angiotensin II (AngII)-induced vascular remodeling model. Our data showed that the intima-media wall of ten-month-old GKO mice but not three-month-olds was significantly thickened compared to wild-type controls. Moreover, ten-month-old GKO mice but not three-month-olds had increased aortic macrophage infiltration and perivascular fibrosis, along with increased endothelial activation and oxidative stress. Similarly, the AngII-induced vascular remodeling, as well as endothelial activation and oxidative stress, were also exacerbated in the GKO mice compared to wild-type controls. In conclusion, we demonstrated that severe HTG caused by Gpihbp1 deficiency could facilitate the onset and progression of non-atherosclerotic vascular remodeling through endothelial activation and oxidative stress in mice. Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Citation

Rui Fan, Xiangbo An, Yao Wang, Jinjin Zhang, Shuang Liu, Jie Bai, Jiatian Li, Qiuyue Lin, Yunpeng Xie, Yunlong Xia, Jiawei Liao. Severe hypertriglyceridemia caused by Gpihbp1 deficiency facilitates vascular remodeling through increasing endothelial activation and oxidative stress. Biochimica et biophysica acta. Molecular and cell biology of lipids. 2023 Jul;1868(7):159330