Serum opacity factor normalizes erythrocyte morphology in Scarb1-/- mice in an HDL-free cholesterol-dependent way

Compared with WT mice, HDL receptordeficient (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 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 adenoassociated 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-FCdependent way. We determined erythrocyte morphology and FC content (mol%) in three groups-WT, untreated Scarb1-/- (control), and these with their respective HDL-mol% FC. Plasma-, HDL-, and tissue-lipid compositions were also determined. Plasma- and HDL-mol% FC positively correlated treatment normalized reticulocyte number, erythrocyte morphology, and erythrocyte-mol% FC. Erythrocyteand 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 erythrocytecomposition by reducing HDL-mol% FC.