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Macrophages exposed to hypoxia secrete proteoglycans for which LDL has higher affinity

Artikel i vetenskaplig tidskrift
Författare Annika Asplund
Vincent Fridén
Pia Stillemark-Billton
German Camejo
Göran Bondjers
Publicerad i ATHEROSCLEROSIS
Volym 215
Nummer/häfte 1
Sidor 77-81
ISSN 0021-9150
Publiceringsår 2011
Publicerad vid Wallenberglaboratoriet
Sidor 77-81
Språk en
Länkar dx.doi.org/10.1016/j.atherosclerosi...
Ämnesord macrophages, hypoxia, ldl-glycosaminoglycans interactions
Ämneskategorier Cell- och molekylärbiologi

Sammanfattning

Macrophages are prominent in hypoxic areas of atherosclerotic lesions. Their secreted proteoglycans (PG) can modulate the retention of lipoproteins as well as the activity of enzymes, cytokines, and growth factors involved in atherogenesis. Versican appears to be one of the main extracellular matrix components binding LDL in the arterial intima. We have recently shown that hypoxia increases versican and perlecan expression in macrophages, and that this increase was regulated by the hypoxia inducible factor (HIF). Here we report effects of hypoxia on human monocyte-derived macrophage (HMDM) secreted glycosaminoglycans (GAG), and its interaction with LDL. After 24 h exposure to 0.5% O2 (hypoxia), metabolically labeled GAG of secreted PG had higher affinity for LDL compared to 21% O2 (control cells). GAG secreted by HMDM in hypoxia were found to be more sulfated and longer which might be responsible for the increased affinity of LDL for these GAG chains. These results indicate that hypoxia induced changes in macrophage GAG biosynthesis have important consequences for the interaction with LDL. If present in vivo, an augmented association of GAG with LDL might contribute to the development of atherosclerosis in hypoxic intima.

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