Original Article

SAA-only HDL formed during the acute phase response in apoA-I^+/+ and apoA-I^-/- mice

Correspondence to: Veneracion G. Cabana

Serum amyloid A (SAA) is an acute phase protein of unknown function that is involved in systemic amyloidosis and may also be involved in atherogenesis. The precise role of SAA in these processes has not been established. SAA circulates in plasma bound to high density lipoprotein-3 (HDL₃). The pathway for the production of SAA-containing HDL is not known. To test whether apolipoprotein (apo)A-I-HDL is required in the production of SAA-HDL, we analyzed the lipopolysaccharide (LPS)-induced changes in apoA-I^+/+ and apoA-I^-/- mice. In apoA-I^+/+ mice, after injection of LPS, remodeling of HDL occurred: total cholesterol increased and apoA-I decreased slightly and shifted to lighter density. Dense (density of HDL₃) but large (size of HDL₂ ) SAA-containing particles were formed. Upon fast phase liquid chromatography fractionation of plasma, >90% of SAA eluted with HDL that was enriched in cholesterol and phospholipid and shifted "leftward" to larger particles. Non-denaturing immunoprecipitation with anti-mouse apoA-I precipitated all of the apoA-I but not all of the SAA, confirming the presence of SAA-HDL devoid of apoA-I. In the apoA-I^-/- mice, which normally have very low plasma lipid levels, LPS injection resulted in significantly increased total and HDL cholesterol. Greater than 90% of the SAA was lipid associated and was found on dense but large, spherical HDL particles essentially devoid of other apolipoproteins.

We conclude that serum amyloid A (SAA) is able to sequester lipid, forming dense but large HDL particles with or without apoA-I or other apolipoproteins. The capacity to isolate lipoprotein particles containing SAA as the predominant or only apolipoprotein provides an important system to further explore the biological function of SAA.—Cabana, V. G., C. A. Reardon, B. Wei, J. R. Lukens, and G. S. Getz. SAA-only HDL formed during the acute phase response in apoA-I^+/+ and apoA-I^-/- mice. J. Lipid Res. 1999. 40: 1090–1103.

Supplementary key words: acute phase response, apoA-I, apoA-I gene knockout mice, cholesterol, HDL, lipoprotein, lipopolysaccharide, mouse plasma lipids, SAA, SAA-only HDL

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. S. Getz and C. A. Reardon SAA, HDL biogenesis, and inflammation J. Lipid Res., February 1, 2008; 49(2): 269 - 270. [Full Text] [PDF]

				W. Hu, S. Abe-Dohmae, M. Tsujita, N. Iwamoto, O. Ogikubo, T. Otsuka, Y. Kumon, and S. Yokoyama Biogenesis of HDL by SAA is dependent on ABCA1 in the liver in vivo J. Lipid Res., February 1, 2008; 49(2): 386 - 393. [Abstract] [Full Text] [PDF]

				M. Heller, E. Schlappritzi, D. Stalder, J.-M. Nuoffer, and A. Haeberli Compositional Protein Analysis of High Density Lipoproteins in Hypercholesterolemia by Shotgun LC-MS/MS and Probabilistic Peptide Scoring Mol. Cell. Proteomics, June 1, 2007; 6(6): 1059 - 1072. [Abstract] [Full Text] [PDF]

				A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF]

				S. Abe-Dohmae, K. H. Kato, Y. Kumon, W. Hu, H. Ishigami, N. Iwamoto, M. Okazaki, C.-A. Wu, M. Tsujita, K. Ueda, et al. Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner J. Lipid Res., July 1, 2006; 47(7): 1542 - 1550. [Abstract] [Full Text] [PDF]

				K. E. Lewis, E. A. Kirk, T. O. McDonald, S. Wang, T. N. Wight, K. D. O'Brien, and A. Chait Increase in Serum Amyloid A Evoked by Dietary Cholesterol Is Associated With Increased Atherosclerosis in Mice Circulation, August 3, 2004; 110(5): 540 - 545. [Abstract] [Full Text] [PDF]

				W. Khovidhunkit, M.-S. Kim, R. A. Memon, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host J. Lipid Res., July 1, 2004; 45(7): 1169 - 1196. [Abstract] [Full Text] [PDF]

				P. W. Connelly, G. F. Maguire, and D. I. Draganov Separation and quantitative recovery of mouse serum arylesterase and carboxylesterase activity J. Lipid Res., March 1, 2004; 45(3): 561 - 566. [Abstract] [Full Text] [PDF]

				V. G. Cabana, N. Feng, C. A. Reardon, J. Lukens, N. R. Webb, F. C. de Beer, and G. S. Getz Influence of apoA-I and apoE on the formation of serum amyloid A-containing lipoproteins in vivo and in vitro J. Lipid Res., February 1, 2004; 45(2): 317 - 325. [Abstract] [Full Text] [PDF]

				V. G. Cabana, C. A. Reardon, N. Feng, S. Neath, J. Lukens, and G. S. Getz Serum paraoxonase: effect of the apolipoprotein composition of HDL and the acute phase response J. Lipid Res., April 1, 2003; 44(4): 780 - 792. [Abstract] [Full Text] [PDF]

				P. C. TUCKER and G. H. SACK JR Expression of serum amyloid A genes in mouse brain: unprecedented response to inflammatory mediators FASEB J, October 1, 2001; 15(12): 2241 - 2246. [Abstract] [Full Text] [PDF]

				C. A. Reardon, L. Blachowicz, T. White, V. Cabana, Y. Wang, J. Lukens, J. Bluestone, and G. S. Getz Effect of Immune Deficiency on Lipoproteins and Atherosclerosis in Male Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 1011 - 1016. [Abstract] [Full Text] [PDF]