Bibliographic Details
| Title: |
Hematopoietic Cell-Specific SLC37A2 Deficiency Accelerates Atherosclerosis in LDL Receptor-Deficient Mice |
| Authors: |
Qingxia Zhao, Zhan Wang, Allison K. Meyers, Jennifer Madenspacher, Manal Zabalawi, Qianyi Zhang, Elena Boudyguina, Fang-Chi Hsu, Charles E. McCall, Cristina M. Furdui, John S. Parks, Michael B. Fessler, Xuewei Zhu |
| Source: |
Frontiers in Cardiovascular Medicine, Vol 8 (2021) |
| Publisher Information: |
Frontiers Media S.A., 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Diseases of the circulatory (Cardiovascular) system |
| Subject Terms: |
glucose 6-phosphate transporter, macrophage inflammation, IL-10, efferocytosis, atherosclerosis, Diseases of the circulatory (Cardiovascular) system, RC666-701 |
| More Details: |
Macrophages play a central role in the pathogenesis of atherosclerosis. Our previous study demonstrated that solute carrier family 37 member 2 (SLC37A2), an endoplasmic reticulum-anchored phosphate-linked glucose-6-phosphate transporter, negatively regulates macrophage Toll-like receptor activation by fine-tuning glycolytic reprogramming in vitro. Whether macrophage SLC37A2 impacts in vivo macrophage inflammation and atherosclerosis under hyperlipidemic conditions is unknown. We generated hematopoietic cell-specific SLC37A2 knockout and control mice in C57Bl/6 Ldlr−/− background by bone marrow transplantation. Hematopoietic cell-specific SLC37A2 deletion in Ldlr−/− mice increased plasma lipid concentrations after 12-16 wks of Western diet induction, attenuated macrophage anti-inflammatory responses, and resulted in more atherosclerosis compared to Ldlr−/− mice transplanted with wild type bone marrow. Aortic root intimal area was inversely correlated with plasma IL-10 levels, but not total cholesterol concentrations, suggesting inflammation but not plasma cholesterol was responsible for increased atherosclerosis in bone marrow SLC37A2-deficient mice. Our in vitro study demonstrated that SLC37A2 deficiency impaired IL-4-induced macrophage activation, independently of glycolysis or mitochondrial respiration. Importantly, SLC37A2 deficiency impaired apoptotic cell-induced glycolysis, subsequently attenuating IL-10 production. Our study suggests that SLC37A2 expression is required to support alternative macrophage activation in vitro and in vivo. In vivo disruption of hematopoietic SLC37A2 accelerates atherosclerosis under hyperlipidemic pro-atherogenic conditions. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2297-055X |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fcvm.2021.777098/full; https://doaj.org/toc/2297-055X |
| DOI: |
10.3389/fcvm.2021.777098 |
| Access URL: |
https://doaj.org/article/faf5fd19e0c94aa199d2c274dfbde07e |
| Accession Number: |
edsdoj.faf5fd19e0c94aa199d2c274dfbde07e |
| Database: |
Directory of Open Access Journals |
