Research ArticleAortic aneurysm

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

See allHide authors and affiliations

Science Translational Medicine  21 Jul 2021:
Vol. 13, Issue 603, eaaz4959
DOI: 10.1126/scitranslmed.aaz4959

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Erythropoietin and AAA

Abdominal aortic aneurysm (AAA) is a common vascular disease, but its pathogenesis has not been fully elucidated. Here, Zhang and colleagues developed a murine model of AAA by administering high doses of erythropoietin, which led to aneurysm formation regardless of ApoE status or angiotensin II infusion, unlike the commonly used murine AAA model. Endothelial cells were critical to erythropoietin’s effects on the aorta, and JAK2/STAT5 pathway activation was implicated in this process. The authors also found a correlation between erythropoietin concentrations and AAA in patients, suggesting that the link between erythropoietin and AAA deserves further investigation in humans.


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.

View Full Text

Stay Connected to Science Translational Medicine