E-selectin inhibition mitigates splenic HSC activation and myelopoiesis in hypercholesterolemic mice with myocardial infarction
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Dutta, Partha
Hoyer, Friedrich Felix
Sun, Yuan
Iwamoto, Yoshiko
Tricot, Benoit
Weissleder, Ralph
Magnani, John
Swirski, Filip
Nahrendorf, Matthias
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https://doi.org/10.1161/ATVBAHA.116.307519Metadata
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Dutta, Partha, Friedrich Felix Hoyer, Yuan Sun, Yoshiko Iwamoto, Benoit Tricot, Ralph Weissleder, John L. Magnani, Filip K. Swirski, and Matthias Nahrendorf. 2016. “E-Selectin Inhibition Mitigates Splenic HSC Activation and Myelopoiesis in Hypercholesterolemic Mice With Myocardial Infarction.” Arteriosclerosis, Thrombosis, and Vascular Biology 36 (9): 1802–8. https://doi.org/10.1161/atvbaha.116.307519.Abstract
Objective Atherosclerosis is a chronic disease characterized by lipid accumulation in the arterial wall. After myocardial infarction (MI), atherosclerotic plaques are infiltrated by inflammatory myeloid cells that aggravate the disease and increase the risk of secondary myocardial ischemia. Splenic myelopoiesis provides a steady flow of myeloid cells to inflamed atherosclerotic lesions after MI. Therefore, targeting myeloid cell production in the spleen could ameliorate increased atherosclerotic plaque inflammation after MI.Approach and Results Here we show that MI increases splenic myelopoiesis by driving hematopoietic stem and progenitor cells into the cell cycle. In an atherosclerotic mouse model, E-selectin inhibition decreased hematopoietic stem and progenitor cell proliferation in the spleen after MI. This led to reduced extramedullary myelopoiesis and decreased myeloid cell accumulation in atherosclerotic lesions. Finally, we observed stable atherosclerotic plaque features, including smaller plaque size, reduced necrotic core area, and thicker fibrous cap after E-selectin inhibition. Conclusions: Inhibiting E-selectin attenuated inflammation in atherosclerotic plaques, likely by reducing leukocyte recruitment into plaques and by mitigating hematopoietic stem and progenitor cell activation in the spleen of mice with MI.Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:41384340
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