Human carotid atherosclerotic plaque protein(s) change HDL protein(s) composition and impair HDL anti‐oxidant activity

Abstract

High density lipoprotein (HDL) anti-atherogenic functions are closely associated with cardiovascular disease risk factor, and are dictated by its composition, which is often affected by environmental factors. The present study investigates the effects of the human carotid plaque constituents on HDL composition and biological functions. To this end, human carotid plaques were homogenized and incubated with HDL. Results showed that after incubation, most of the apolipoprotein A1 (Apo A1) protein was released from the HDL, and HDL diameter increased by an average of approximately 2 nm. In parallel, HDL antioxidant activity was impaired. In response to homogenate treatment HDL could not prevent the accelerated oxidation of LDL caused by the homogenate. Boiling of the homogenate prior to its incubation with HDL abolished its effects on HDL composition changes. Moreover, tryptophan fluorescence quenching assay revealed an interaction between plaque component(s) and HDL, an interaction that was reduced by 50% upon using pre-boiled homogenate. These results led to hypothesize that plaque protein(s) interacted with HDL-associated Apo A1 and altered the HDL composition. Immuno-precipitation of Apo A1 that was released from the HDL after its incubation with the homogenate revealed a coprecipitation of three isomers of actin. However, beta-actin alone did not significantly affect the HDL composition, and yet the active protein within the plaque was elusive. In conclusion then, protein(s) in the homogenate interact with HDL protein(s), leading to release of Apo A1 from the HDL particle, a process that was associated with an increase in HDL diameter and with impaired HDL anti-oxidant activity.

Paraoxonase 1, HDL Subclasses and Post Surgery Acute Inflammation: A Pilot Study

“…Studies have also shown that PON1, an antioxidant marker, and SAA, an inflammation marker, move in opposite directions and indicate dysfunctional and a more proatherogenic form of HDL [15,23]. Inflammation and oxidative stress coexist in patients with chronic disease [15,24] and under these conditions native HDL may be converted into dysfunctional HDL [7,25] with altered proteins. These changes may contribute to the less protective and more atherogenic nature of HDL [15].…”

“…In addition to its reverse cholesterol transport and cholesterol efflux activity, HDL has various endothelial promoting and cardio-protective properties; it is antithrombotic, anti-inflammatory and an antioxidant [7,8,9]. PON1, an enzyme found mostly in bound form to HDL [10], in association with ApoA-1 [11], affords antioxidant capacity to HDL and may explain, in part, its anti-atherogenic function [12,13].…”

Anti-Atherogenic Properties of Allium ursinum Liophylisate: Impact on Lipoprotein Homeostasis and Cardiac Biomarkers in Hypercholesterolemic Rabbits

“…Thus, the lack of significant differences in the ApoA content of blood from animals fed normal diets (control) versus the content of this molecule in WGLL-treated rabbits maintained on high cholesterol (HCT) indicated a normalizing effect of the lyophilisate on this outcome. The significance of this result is that ApoA-I deficiency causes both hypertriglyceridemia and increased atherosclerosis in animal models [44], which can be counteracted by a WGLL-supported diet.…”

Association Between Plasma Lipids Profile and Lipids Oxidizability in Healthy Men

“…16 Another finding observed in this study was an inverse relationship between HDL concentration and the lag time, which indicates that HDL reduces resistance to oxidizability process. 16,20 The most epidemiological studies indicate that plasma HDL is considered as a protective factor against coronary heart disease. The prevalence of atherosclerosis has been reported to be lower in the patients with high HDL levels.…”