Effects of serum amyloid A on the structure and antioxidant ability of high-density lipoprotein

Abstract

Serum amyloid A (SAA) levels increase during acute and chronic inflammation and are mainly associated with high-density lipoprotein (HDL). In the present study, we investigated the effect of SAA on the composition, surface charge, particle size and antioxidant ability of HDL using recombinant human SAA (rhSAA) and HDL samples from patients with inflammation. We confirmed that rhSAA bound to HDL3 and released apolipoprotein A-I (apoA-I) from HDL without an apparent change in particle size. Forty-one patients were stratified into three groups based on serum SAA concentrations: Low (SAA ≤ 8 μg/ml), Middle (8 < SAA ≤ 100 μg/ml) and High (SAA > 100 μg/ml). The ratios of apoA-I to total protein mass, relative cholesterol content and negative charge of HDL samples obtained from patients with high SAA levels were lower than that for samples from patients with low SAA levels. Various particle sizes of HDL were observed in three groups regardless of serum SAA levels. Antioxidant ability of rhSAA, evaluated as the effect on the formation of conjugated diene in low-density lipoprotein (LDL) induced by oxidation using copper sulfate, was higher than that of apoA-I. Consistent with this result, reconstituted SAA-containing HDL (SAA-HDL) indicated higher antioxidant ability compared with normal HDL. Furthermore, HDL samples obtained from High SAA group patients also showed the highest antioxidant ability among the three groups. Consequently, SAA affects the composition and surface charge of HDL by displacement of apoA-I and enhances its antioxidant ability.

Paradoxical effects of SAA on lipoprotein oxidation suggest a new antioxidant function for SAA

“…Although the anti-oxidant effect of apoA-I on LDL is well-established, to our knowledge this is one of the first reports of a similar, but smaller, effect of free SAA on LDL (Fig. 4B), along with a very recent study by Sato et al (24) reporting that SAA decelerates copper-induced LDL oxidation. Both our study and the study by Sato et al also show that SAA decelerates copper-induced HDL oxidation in a dose-dependent manner ( Figs.…”

“…In this work, we determined the combined effects of SAA enrichment and oxidation by various oxidative agents on the biochemical and biophysical modifications in HDL and LDL, with the main focus on HDL. Concurrently, Sato et al (24) reported, for the first time, that human SAA retards the copper-induced oxidation of HDL and LDL. Together, these results indicate that SAA partially compensates for the loss of anti-oxidant HDL proteins, suggest a new physiological function for SAA as a mild anti-oxidant for lipids, and shed new light on the complex role of SAA in lipid oxidation and human disease.…”

High-Density Lipoprotein (HDL) Inhibits Serum Amyloid A (SAA)-Induced Vascular and Renal Dysfunctions in Apolipoprotein E-Deficient Mice

“…Under inflammatory conditions, SAA displaces ApoA-I, the predominant apolipoprotein of HDL. Although debated in the literature [23,55], at least some of the available data [56][57][58] indicate that this mode of ApoA-I displacement alters HDL function and effectively promotes a pro-atherogenic phenotype at a threshold when SAA constitutes more than half of the HDL protein [59]. Therefore, it is hypothesized that the ratio of SAA/HDL is important for HDL anti-inflammatory and antioxidant activities in biological systems.…”

“…HDL also inhibits SAA-mediated reactive oxygen species generation and Nod-like receptor protein 3 (NLRP3) inflammasome activation [22]. Nonetheless, others have reported contradictory results showing that reconstituted HDL containing SAA showed higher antioxidant potential than normal HDL [23] and that SAA bound by HDL exhibited no discernible cytotoxicity under pathophysiological conditions [24].…”

Dynamic changes of the composition of plasmaHDLparticles in patients with cardiac disease: Spotlight on sphingosine‐1‐phosphate/serum amyloid A ratio

“…54 HDL cell-cholesterol efflux capacity (CEC) has been inversely linked to ASCVD. [64][65][66] The primary methods of cell-cholesterol efflux are via ABCA1 and scavenger receptor class B type I (SR-BI). 67 Studying the activity of these has allowed for a better understanding of cholesterol transport.…”