Abstract
Modifications in high-density lipoprotein (HDL) particle sizes and HDL-binding proteins have been reported in stroke patients. We evaluated whether the lipoprotein profile, HDL composition and functionality were altered in stroke patients according to their clinical outcome using the modified Rankin Score at 3 months. Plasma samples were obtained from stroke patients treated with intravenous thrombolysis. Levels of cardiovascular and inflammatory markers in plasma were measured using the Human CVD Panel 1 (Milliplex® MAP). Lipoprotein subfractions from plasma were quantified by non-denaturing acrylamide gel electrophoresis, using the Lipoprint®-System (Quantimetrix®), and HDLs were isolated by ultracentrifugation. Relative amounts of paraoxonase-1 (PON1) and alpha-1 anti-trypsin (AAT) in the isolated HDLs were determined by Western blot. HDL anti-inflammatory function was evaluated in human blood–brain barrier endothelial cells stimulated with 100 ng/mL TNFα, and HDL antioxidant function was evaluated via their capacity to limit copper-induced low-density lipoprotein oxidation. Stroke patients with unfavorable outcomes had a lower proportion of small-sized HDLs and increased plasma levels of E-selectin (SELE) and the intercellular adhesion molecule 1 (ICAM1). HDLs from patients with unfavorable outcomes had lower levels of PON1 and displayed a blunted capacity to reduce the expression of SELE, interleukin 8 (IL8) and the monocyte chemoattractant protein-1 (MCP1) mRNA induced by TNFα in endothelial cells. These HDLs also had a reduced antioxidant capacity relative to HDLs from healthy donors. In conclusion, an increased ratio of large/small HDLs with impaired anti-inflammatory and antioxidant capacities was associated with unfavorable outcomes in stroke patients. Alteration of HDL functionality was mainly associated with a low amount of PON1 and high amount of AAT.
Highlights
High-density lipoproteins (HDL) are highly heterogeneous in size, shape and composition [1,2]
Since HDL particles may participate in the pathology of stroke and potentially limit subsequent brain damage, the aim of the present study was to evaluate whether the lipoprotein profile, HDL composition and functionality were altered in stroke patients according to their clinical outcome, determined using the modified Rankin Score at 3 months
We found that alpha-1 anti-trypsin (AAT) was more abundant in HDLs from stroke patients compared to healthy controls, but no differences related to the outcome were found
Summary
High-density lipoproteins (HDL) are highly heterogeneous in size, shape and composition [1,2]. HDL subfractions differ in their ability to exert their antiatherogenic functions (cholesterol removal, anti-inflammatory, antioxidant and endothelial cell protection) [4]. Some of the identified proteins related to HDL functions are paraoxonase-1 (PON1) and alpha-1 anti-trypsin (AAT), which show antioxidant and anti-inflammatory properties, respectively [6,7,8]. AAT is an acute-phase reactive plasma protein that belongs to the family of serine protease inhibitors. It is the main physiological inhibitor of neutrophil elastase, an enzyme produced by activated neutrophils in atherosclerotic lesions, which degrades extracellular matrix components and stimulates the production of pro-inflammatory cytokines that contribute to plaque instability [11,12]
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