1. Academic Validation
  2. Erythropoietin promotes abdominal aortic aneurysms in mice through angiogenesis and inflammatory infiltration

Erythropoietin promotes abdominal aortic aneurysms in mice through angiogenesis and inflammatory infiltration

  • Sci Transl Med. 2021 Jul 21;13(603):eaaz4959. doi: 10.1126/scitranslmed.aaz4959.
Meng Zhang 1 Wenhai Sui 1 Cheng Cheng 1 Fei Xue 1 Zhenyu Tian 1 Jing Cheng 1 Jie Zhang 1 Tao Zhang 2 Jianlin Zhang 1 Weiwei Wang 1 Wenjing Xiong 1 Panpan Hao 1 Jing Ma 1 Xingli Xu 1 Shuangxi Wang 1 Shangwen Sun 1 Meng Zhang 3 Yun Zhang 3 Cheng Zhang 3
Affiliations

Affiliations

  • 1 Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.
  • 2 Department of Vascular Surgery, First Affiliated Hospital of Shandong First Medical University, Jinan 250013, Shandong, China.
  • 3 Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China. [email protected] [email protected] [email protected].
Abstract

Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease, but the underlying mechanisms remain unknown. Here, we tested the hypothesis that erythropoietin (EPO) may promote the formation of AAA. We found that EPO dose-dependently promoted the formation of AAA in both Apoe -/- (66.7%) and wild-type (WT) (60%) mice receiving a high dose of EPO. EPO monoclonal Antibodies given to Apoe -/- mice receiving angiotensin II (AngII) stimulation resulted in a markedly lower incidence of AAA (from 86.7 to 20%, P < 0.001), and EPO receptor (EPOR) knockdown in Epor +/- Apoe -/- mice substantially reduced the incidence of AAA compared to Apoe -/- mice after AngII stimulation (from 86.7 to 45.5%, P < 0.05), further supporting the finding that EPO is a contributor to AAA formation. EPO-induced AAA resulted in increased microvessels, phagocyte infiltration, and matrix metalloproteinase secretion, as well as reduced collagen and smooth muscle cells (SMCs). Experiments in vitro and ex vivo demonstrated that EPO induced proliferation, migration, and tube formation of endothelial cells via the JAK2/STAT5 signaling pathway. In humans, serum EPO concentrations were higher in patients with AAA than in healthy individuals and correlated with the size of the AAA, suggesting a potential link between EPO and the severity of AAA in humans. In conclusion, we found that EPO promotes the formation of AAA in both Apoe -/- and WT mice by enhancing angiogenesis, inflammation, collagen degradation, and Apoptosis of SMCs and that EPO/EPOR signaling is essential for AngII-induced AAA. The association between EPO and AAA in humans warrants further study.

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