High-Density Lipoproteins and Serum Amyloid A (SAA)

Abstract

Purpose of Review Serum amyloid A (SAA) is a highly sensitive acute phase reactant that has been linked to a number of chronic inflammatory diseases. During a systemic inflammatory response, liver-derived SAA is primarily found on high-density lipoprotein (HDL). The purpose of this review is to discuss recent literature addressing the pathophysiological functions of SAA and the significance of its association with HDL. Recent Findings Studies in gene-targeted mice establish that SAA contributes to atherosclerosis and some metastatic cancers. Accumulating evidence indicates that the lipidation state of SAA profoundly affects its bioactivities, with lipid-poor, but not HDL-associated, SAA capable of inducing inflammatory responses in vitro and in vivo. Factors that modulate the equilibrium between lipid-free and HDL-associated SAA have been identified. Summary HDL may serve to limit SAA’s bioactivities in vivo. Understanding the factors leading to the release of systemic SAA from HDL may provide insights into chronic disease mechanisms.

The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective

“…The incidental findings of prostatic amyloid transthyretin refers to cardiac amyloidosis [104], as opposed to the serum amyloid A [101][102][103]. Amyloidosis results from the accumulation of pathogenic amyloid, most of which are aggregates of misfolded proteins in a variety of tissues, which interferes with their normal physiology and function in chronic inflammatory diseases [103,[105][106][107][108][109][110]. It forms the amyloid senescence cascade hypothesis and is harmful to the non-senescent surrounding cells [111].…”

Role of Serum Amyloid A in Abdominal Aortic Aneurysm and Related Cardiovascular Diseases

“…Pro-inflammatory cytokines such as Interleukin-1β (IL-1β), Interleukin-6 (IL-6), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) serve as regulators in hepatic production of SAA during the acute-phase response [ 1 , 12 ]. SAA is also induced by inflammatory stimuli in other cell types, including adipocytes, muscle cells, and intestinal cells [ 24 ]. IL-6 seems to be the most critical stimulus of SAA early in the acute-phase response, but the combined activity of all factors gives the highest level of transcription [ 1 ].…”

“…The majority of liver-derived SAA is typically found associated with high-density lipoprotein (HDL) fraction [ 52 , 53 , 54 ]. During severe inflammation, SAA can become the major apolipoprotein on HDL [ 24 ]. The presence of SAA on HDL affects properties of both SAA and HDL.…”

Serum Amyloid A Correlates With the Osteonecrosis of Femoral Head by Affecting Bone Metabolism

“…In particular, SAA is involved with cholesterol metabolism in both physiologic and inflammatory conditions ( Sack, 2018 ). Clearly, the intimate relationship among SAA/HDL/cholesterol has implicated SAA in the pathogenesis of various diseases, such as rheumatoid arthritis ( Mun et al, 2021 ), atherosclerosis ( Webb, 2021 ), alcoholic liver cirrhosis ( Kim et al, 2014 ) and insulin resistance ( Li et al, 2021 ). Mechanistically, SAA participates in the processes of the above diseases by binding with HDL, promoting adipogenic differentiation and promoting the proliferation of preadipocytes.…”