title: Apolipoprotein AI deficiency inhibits serum opacity factor activity against plasma high density lipoprotein via a stabilization mechanism.
abstract: The reaction of Streptococcal serum opacity factor (SOF) against plasma high-density lipoproteins (HDL) produces a large cholesteryl ester-rich microemulsion (CERM), a smaller neo HDL that is apolipoprotein (apo) AI-poor, and lipid-free apo AI. SOF is active versus both human and mouse plasma HDL. In vivo injection of SOF into mice reduces plasma cholesterol ∼40% in 3 h while forming the same products observed in vitro, but at different ratios. Previous studies supported the hypothesis that labile apo AI is required for the SOF reaction vs HDL. Here we further tested that hypothesis by studies of SOF against HDL from apo AI-null mice. When injected into apo AI-null mice, SOF reduced plasma cholesterol ∼35% in 3 h. The reaction of SOF vs apo AI-null HDL in vitro produced a CERM and neo HDL, but no lipid-free apo. Moreover, according to the rate of CERM formation, the extent and rate of the SOF reaction versus apo AI-null mouse HDL were less than that against wild-type (WT) mouse HDL. Chaotropic perturbation studies using guanidine hydrochloride showed that apo AI-null HDL was more stable than WT HDL. Human apo AI added to apo AI-null HDL was quantitatively incorporated, giving reconstituted HDL. Both SOF and guanidine hydrochloride displaced apo AI from the reconstituted HDL. These results support the conclusion that apo AI-null HDL is more stable than WT HDL because it lacks apo AI, a labile protein that is readily displaced by physicochemical and biochemical perturbations. Thus, apo AI-null HDL is less SOF-reactive than WT HDL. The properties of apo AI-null HDL can be partially restored to those of WT HDL by the spontaneous incorporation of human apo AI. It remains to be determined what other HDL functions are affected by apo AI deletion.
authors: †Laboratory of Atherosclerosis and Lipoprotein Research, Department of Cardiology, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.
authors: Corina
authors: C
authors: Rosales
authors: †Laboratory of Atherosclerosis and Lipoprotein Research, Department of Cardiology, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.
authors: Niket
authors: N
authors: Patel
authors: †Laboratory of Atherosclerosis and Lipoprotein Research, Department of Cardiology, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.
authors: Baiba K
authors: BK
authors: Gillard
authors: †Laboratory of Atherosclerosis and Lipoprotein Research, Department of Cardiology, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.
authors: Dedipya
authors: D
authors: Yelamanchili
authors: †Laboratory of Atherosclerosis and Lipoprotein Research, Department of Cardiology, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.
authors: Yaliu
authors: Y
authors: Yang
authors: ‡Veterans Affairs Medical Center and Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38104, United States.
authors: Harry S
authors: HS
authors: Courtney
authors: §Heart Institute-INCOR, University of Sao Paulo, 05409-003 Sao Paulo, Brazil.
authors: Raul D
authors: RD
authors: Santos
authors: †Laboratory of Atherosclerosis and Lipoprotein Research, Department of Cardiology, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.|⊥Weill Cornell Medical College, 1305 York Avenue, New York, New York 10021, United States.
authors: Antonio M
authors: AM
authors: Gotto
authors: †Laboratory of Atherosclerosis and Lipoprotein Research, Department of Cardiology, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.|⊥Weill Cornell Medical College, 1305 York Avenue, New York, New York 10021, United States.
authors: Henry J
authors: HJ
authors: Pownall
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000235:genetics; D019791:Guanidine / Q000737:chemistry; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry*; D018345:Mice, Knockout; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; C021908:opacity factor; D010447:Peptide Hydrolases; D019791:Guanidine