Abstract
Neutrophil extracellular traps (NETs) are DNA–protein structures released by neutrophils in response to various stimuli, including oxidized, low-density lipoprotein (oxLDL). Accumulating evidence suggests a role for NETs in the pathogenesis of abdominal aortic aneurysm (AAA). In this study, we investigated the potential association of lipoprotein particles and NETs in AAA in comparison to non-AAA control groups. The concentrations of neutrophil myeloperoxidase (MPO), the NET parameters citrullinated histone H3 (citH3) and circulating cell-free DNA (cfDNA), as well as of blood lipids were determined in plasma or serum of patients with AAA (n = 40), peripheral artery occlusive disease (PAD; n = 40) and healthy donors (n = 29). A sandwich ELISA detecting oxidized phosphatidylcholine in association with apolipoprotein B-100 (oxPL/apoB) was applied to measure oxidized phospholipids in circulation. The effect of lipoparticles on NET formation was tested using a DNA release assay with isolated human neutrophils. Plasma MPO, citH3 and cfDNA levels were significantly increased in AAA patients in comparison to healthy donors and PAD patients. Plasma concentrations of citH3 positively correlated with serum oxPL/apoB in AAA patients. In functional in vitro assays, the addition of oxLDL induced NET formation in pre-stimulated neutrophils. In conclusion, our data suggest a promoting role of oxLDL on NET formation in AAA patients.
Highlights
The healthy controls (H) had a significantly lower percentage of current or past smokers compared to the two cardiovascular disease (CVD) cohorts (H: 69%, peripheral artery occlusive disease (PAD): 93% and abdominal aortic aneurysm (AAA): 93%)
Our study evaluated the interrelation of lipoprotein particles with Neutrophil extracellular traps (NETs) parameters in patients with abdominal aortic aneurysm as compared to peripheral artery occlusive disease and healthy controls
We found that neutrophil activation and NET parameters are higher in blood of AAA than PAD patients and that the serum concentration of oxPL/apoB
Summary
Abdominal aortic aneurysm (AAA) is a precarious condition, as patients are often asymptomatic, while the risk of rupture remains a constant threat and leads to death in 80%. It is vital to further improve our knowledge on the pathogenesis of this aortic dilatation, so that future therapies can have a causal mode of action and be effective before surgery is indicated. It is known that immune cells, neutrophils, accumulate in the intraluminal thrombus and adventitia of the AAA and contribute to the progression of disease [2]. Neutrophils release proteolytic enzymes and cause oxidative stress, thereby promoting the degradation of elastin fibers and the death of smooth muscle cells in the aortic wall [3,4]
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