English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Background  The liver X receptors ( LXRs ; α/β) are nuclear receptors known to regulate cholesterol homeostasis and the production of select hematopoietic populations. The objective of this study was to determine the importance of  LXR s and a high‐fat high‐cholesterol diet on global hematopoiesis, with special emphasis on endothelial progenitor cells ( EPC s), a vasoreparative cell type that is derived from bone marrow hematopoietic stem cells.    Methods and Results  Wild‐type and  LXR  double‐knockout ( Lxr αβ  −/−  ) mice were fed a Western diet ( WD ) to increase plasma cholesterol levels. In  WD ‐fed  Lxr αβ  −/−   mice, flow cytometry and complete blood cell counts revealed that hematopoietic stem cells, a myeloid progenitor, and mature circulating myeloid cells were increased;  EPC  numbers were significantly decreased. Hematopoietic stem cells from  WD ‐fed  Lxr αβ  −/−   mice showed increased cholesterol content, along with increased myeloid colony formation compared with chow‐fed mice. In contrast,  EPC s from  WD ‐fed  Lxr αβ  −/−   mice also demonstrated increased cellular cholesterol content that was associated with greater expression of the endothelial lineage markers  Cd144  and  Vegfr2 , suggesting accelerated differentiation of the  EPC s. Treatment of human umbilical vein endothelial cells with conditioned medium collected from these  EPC s increased  THP ‐1 monocyte adhesion. Increased monocyte adhesion to conditioned medium–treated endothelial cells was recapitulated with conditioned medium from  Lxr αβ  −/−    EPC s treated with cholesterol ex vivo, suggesting cholesterol is the main component of the  WD  inducing  EPC  dysfunction.    Conclusions   LXR s are crucial for maintaining the balance of hematopoietic cells in a hypercholesterolemic environment and for mitigating the negative effects of cholesterol on  EPC  differentiation/secretome changes that promote monocyte‐endothelial adhesion.

Loss of the Liver X Receptors Disrupts the Balance of Hematopoietic Populations, With Detrimental Effects on Endothelial Progenitor Cells