The turning away of serum amyloid A biological activities and receptor usage

The acute phase reactant serum amyloid A (SAA) is an HDL apolipoprotein that exhibits biological activities as a pro-inflammatory mediator, but its physiological function(s) are poorly understood. Possible functional differences between SAA1.1 and SAA2.1, the two major SAA isoforms, are also unclear. Mice deficient in either SAA1.1 or SAA2.1 were used to investigate SAA isoform plasma clearance rates and effects on HDL structure, composition and apolipoprotein catabolism. The absence of either isoform did not affect the size of the normally enlarged HDL found in acute phase wild type mice, and did not result in significant changes in HDL lipid composition. Plasma clearance rates of normal and acute phase HDL apolipoproteins were determined using native HDL particles. The fractional clearance rates (FCR’s) of apoA-I, apoA-II and SAA were distinct, indicating that neither normal nor acute phase particles are cleared as intact particles. No significant difference was found between the FCR’s of SAA1.1 and SAA2.1 in acute phase mice, suggesting that the selective deposition of SAA1.1 observed in amyloid plaques is not associated with a difference in the rates of plasma clearance of the isoforms. In the absence of the HDL receptor SR-BI, the clearance rate of SAA was reduced by about 30% and remained significantly greater compared to that of apoA-I and apoA-II, indicating a relatively minor role of SR-BI in SAA clearance. These studies contribute to our understanding of the metabolism of SAA and its effects on acute phase HDL composition and catabolism.

Download Full-text

The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality

Biological Chemistry ◽

10.1515/hsz-2014-0192 ◽

2015 ◽

Vol 396 (6-7) ◽

pp. 573-583 ◽

Cited By ~ 15

Author(s):

Nicole Prüfer ◽

Burkhard Kleuser ◽

Markus van der Giet

Keyword(s):

High Density Lipoprotein ◽

Acute Phase ◽

Serum Amyloid A ◽

Biological Activities ◽

Density Lipoprotein ◽

High Density ◽

Serum Amyloid ◽

Amyloid A ◽

Hdl Function ◽

Sphingosine 1 Phosphate

Abstract The high-density lipoprotein (HDL) is one of the most important endogenous cardiovascular protective markers. HDL is an attractive target in the search for new pharmaceutical therapies and in the prevention of cardiovascular events. Some of HDL’s anti-atherogenic properties are related to the signaling molecule sphingosine-1-phosphate (S1P), which plays an important role in vascular homeostasis. However, for different patient populations it seems more complicated. Significant changes in HDL’s protective potency are reduced under pathologic conditions and HDL might even serve as a proatherogenic particle. Under uremic conditions especially there is a change in the compounds associated with HDL. S1P is reduced and acute phase proteins such as serum amyloid A (SAA) are found to be elevated in HDL. The conversion of HDL in inflammation changes the functional properties of HDL. High amounts of SAA are associated with the occurrence of cardiovascular diseases such as atherosclerosis. SAA has potent pro-atherogenic properties, which may have impact on HDL’s biological functions, including cholesterol efflux capacity, antioxidative and anti-inflammatory activities. This review focuses on two molecules that affect the functionality of HDL. The balance between functional and dysfunctional HDL is disturbed after the loss of the protective sphingolipid molecule S1P and the accumulation of the acute-phase protein SAA. This review also summarizes the biological activities of lipid-free and lipid-bound SAA and its impact on HDL function.

Download Full-text