Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.).
Published: November 2015
AI Article Synopsis
Article Abstract
Background: High-fat diet (HFD) promotes endothelial dysfunction and proinflammatory monocyte activation, which contribute to atherosclerosis in obesity. We investigated whether HFD also induces the dysfunction of red blood cells (RBCs), which serve as a reservoir for chemokines via binding to Duffy antigen receptor for chemokines (DARC).
Methods And Results: A 60% HFD for 12 weeks, which produced only minor changes in lipid profile in C57/BL6 mice, markedly augmented the levels of monocyte chemoattractant protein-1 bound to RBCs, which in turn stimulated macrophage migration through an endothelial monolayer. Levels of RBC-bound KC were also increased by HFD. These effects of HFD were abolished in DARC(-/-) mice. In RBCs from HFD-fed wild-type and DARC(-/-) mice, levels of membrane cholesterol and phosphatidylserine externalization were increased, fostering RBC-macrophage inflammatory interactions and promoting macrophage phagocytosis in vitro. When labeled ex vivo and injected into wild-type mice, RBCs from HFD-fed mice exhibited ≈3-fold increase in splenic uptake. Finally, RBCs from HFD-fed mice induced increased macrophage adhesion to the endothelium when they were incubated with isolated aortic segments, indicating endothelial activation.
Conclusions: RBC dysfunction, analogous to endothelial dysfunction, occurs early during diet-induced obesity and may serve as a mediator of atherosclerosis. These findings may have implications for the pathogenesis of atherosclerosis in obesity, a worldwide epidemic.
