Details

Autor(en) / Beteiligte

• Wang, Ziyi
• Yelamanchili, Dedipya
• Liu, Jing
• Gotto, Antonio M.
• Rosales, Corina
• Gillard, Baiba K.
• Pownall, Henry J.

Titel

Serum Opacity Factor Normalizes Erythrocyte Morphology in Scarb1-/- Mice in an HDL-Free Cholesterol-Dependent Way

Ist Teil von

• Journal of lipid research, 2023-11, Vol.64 (11), p.100456-100456, Article 100456

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Compared to wild-type (WT) mice, high-density lipoprotein (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. [Display omitted]