Redox Biology (Sep 2020)
Angiogenic and Antiangiogenic mechanisms of high density lipoprotein from healthy subjects and coronary artery diseases patients
- Hua-Ming Li,
- Zhi-Wei Mo,
- Yue-Ming Peng,
- Yan Li,
- Wei-Ping Dai,
- Hai-Yun Yuan,
- Feng-Jun Chang,
- Tian-Tian Wang,
- Mian Wang,
- Kun-Hua Hu,
- Xiao-Di Li,
- Da-Sheng Ning,
- Ya-Ting Chen,
- Yuan-Kai Song,
- Xi-Lin Lu,
- Zhong Pei,
- Yu-Gang Dong,
- Zhi-Ping Wang,
- Xi Zhang,
- Ying-Qi Xu,
- Shen-Ming Wang,
- Zhi-Jun Ou,
- Jing-Song Ou
Affiliations
- Hua-Ming Li
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Zhi-Wei Mo
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Yue-Ming Peng
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Yan Li
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Wei-Ping Dai
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Hai-Yun Yuan
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Feng-Jun Chang
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Tian-Tian Wang
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Mian Wang
- National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China
- Kun-Hua Hu
- Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, 510080, PR China; Proteomics Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, PR China
- Xiao-Di Li
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Da-Sheng Ning
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Ya-Ting Chen
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Yuan-Kai Song
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Xi-Lin Lu
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China
- Zhong Pei
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China
- Yu-Gang Dong
- National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Department of Cardiology, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China
- Zhi-Ping Wang
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Xi Zhang
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Ying-Qi Xu
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China
- Shen-Ming Wang
- National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China
- Zhi-Jun Ou
- National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; Division of Hypertension and Vascular Diseases, Department of Cardiology, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; Corresponding author. Division of Hypertension and Vascular Diseases The First Affiliated Hospital, Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, PR China.
- Jing-Song Ou
- Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, 510080, PR China; Corresponding author. Division of Cardiac Surgery , The First Affiliated Hospital, Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, PR China.
- Journal volume & issue
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Vol. 36
p. 101642
Abstract
Normal high-density lipoprotein (nHDL) in normal, healthy subjects is able to promote angiogenesis, but the mechanism remains incompletely understood. HDL from patients with coronary artery disease may undergo a variety of oxidative modifications, rendering it dysfunctional; whether the angiogenic effect is mitigated by such dysfunctional HDL (dHDL) is unknown. We hypothesized that dHDL compromises angiogenesis. The angiogenic effects of nHDL and dHDL were assessed using endothelial cell culture, endothelial sprouts from cardiac tissue from C57BL/6 mice, zebrafish model for vascular growth and a model of impaired vascular growth in hypercholesterolemic low-density lipoprotein receptor null(LDLr-/-)mice. MiRNA microarray and proteomic analyses were used to determine the mechanisms. Lipid hydroperoxides were greater in dHDL than in nHDL. While nHDL stimulated angiogenesis, dHDL attenuated these responses. Protein and miRNA profiles in endothelial cells differed between nHDL and dHDL treatments. Moreover, nHDL suppressed miR-24-3p expression to increase vinculin expression resulting in nitric oxide (NO) production, whereas dHDL delivered miR-24-3p to inhibit vinculin expression leading to superoxide anion (O2•-) generation via scavenger receptor class B type 1. Vinculin was required for endothelial nitric oxide synthase (eNOS) expression and activation and modulated the PI3K/AKT/eNOS and ERK1/2 signaling pathways to regulate nHDL- and VEGF-induced angiogenesis. Vinculin overexpression or miR-24-3p inhibition reversed dHDL-impaired angiogenesis. The expressions of vinculin and eNOS and angiogenesis were decreased, but the expression of miR-24-3p and lipid hydroperoxides in HDL were increased in the ischemic lower limbs of hypercholesterolemic LDLr-/- mice. Overexpression of vinculin or miR-24-3p antagomir restored the impaired-angiogenesis in ischemic hypercholesterolemic LDLr-/- mice. Collectively, nHDL stimulated vinculin and eNOS expression to increase NO production by suppressing miR-24-3p to induce angiogenesis, whereas dHDL inhibited vinculin and eNOS expression to enhance O2•- generation by delivering miR-24-3p to impair angiogenesis, and that vinculin and miR-24-3p may be therapeutic targets for dHDL-impaired angiogenesis.