Autor: |
Ziyi Wang, Dedipya Yelamanchili, Jing Liu, Antonio M. Gotto, Jr., Corina Rosales, Baiba K. Gillard, Henry J. Pownall |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Journal of Lipid Research, Vol 64, Iss 11, Pp 100456- (2023) |
Druh dokumentu: |
article |
ISSN: |
0022-2275 |
DOI: |
10.1016/j.jlr.2023.100456 |
Popis: |
Compared with WT mice, HDL receptor-deficient (Scarb1−/−) mice have higher plasma levels of free cholesterol (FC)-rich HDL and exhibit multiple pathologies associated with a high mol% FC in ovaries, platelets, and erythrocytes, which are reversed by lowering HDL. Bacterial serum opacity factor (SOF) catalyzes the opacification of plasma by targeting and quantitatively converting HDL to neo HDL (HDL remnant), a cholesterol ester-rich microemulsion, and lipid-free APOA1. SOF delivery with an adeno-associated virus (AAVSOF) constitutively lowers plasma HDL-FC and reverses female infertility in Scarb1−/− mice in an HDL-dependent way. We tested whether AAVSOF delivery to Scarb1−/− mice will normalize erythrocyte morphology in an HDL-FC-dependent way. We determined erythrocyte morphology and FC content (mol%) in three groups—WT, untreated Scarb1−/− (control), and Scarb1−/− mice receiving AAVSOF—and correlated these with their respective HDL-mol% FC. Plasma-, HDL-, and tissue-lipid compositions were also determined. Plasma- and HDL-mol% FC positively correlated across all groups. Among Scarb1−/− mice, AAVSOF treatment normalized reticulocyte number, erythrocyte morphology, and erythrocyte-mol% FC. Erythrocyte-mol% FC positively correlated with HDL-mol% FC and with both the number of reticulocytes and abnormal erythrocytes. AAVSOF treatment also reduced FC of extravascular tissues to a lesser extent. HDL-FC spontaneously transfers from plasma HDL to cell membranes. AAVSOF treatment lowers erythrocyte-FC and normalizes erythrocyte morphology and lipid composition by reducing HDL-mol% FC. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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