Myeloperoxidase in atrial fibrillation: association with progression, origin and influence of renin–angiotensin system antagonists

Holzwirth, Erik; Kornej, Jelena; Erbs, Sandra; Obradović, Danilo; Bollmann, Andreas; Hindricks, Gerhard; Thiele, Holger; Büttner, Petra

doi:10.1007/s00392-019-01512-z

Cited by 22 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is in line with results from our previous study where we observed that elevated MPO levels in AF patients are independent from the AF progression phenotype and also the rhythm outcome following catheter ablation [30]. Therefore, we hypothesized that MPO might be involved in the initiation of fibrotic processes but is not directly associated with the extent of fibrotic remodelling in AF [30]. Likewise, MPO may contribute to the observed HDL dysfunction in AF but also other yet unrecognized factors that were not measured in our study may be of importance.…”

Section: Possible Mechanisms Of Hdl Impairmentsupporting

confidence: 93%

“…As endothelial dysfunction and the associated chronic inflammation are a well described phenomena in AF [ 26 ] we chose endothelial cells over other cardiac tissues as a model of the atria for our experiments. Inflammatory hallmarks of AF include increased macrophage infiltration and cytokine deposition into atrial tissue [ 27 ] and elevated levels of circulating interleukin-6 [ 28 ], TNF-α [ 29 ], and MPO [ 30 , 31 ]. Aside from stimulating the expression of pro-inflammatory cytokines, TNF-α has been found to be a driver of chronic electro-anatomical remodelling [ 32 ] as well as short-term alterations in ion currents [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Anti-inflammatory HDL effects are impaired in atrial fibrillation

et al. 2021

Self Cite

View full text Add to dashboard Cite

High-density lipoprotein (HDL), best known for cholesterol transport, also has anti-inflammatory effects. Previous studies suggest involvement of myeloperoxidase (MPO) in modification of HDL. HDL bound Sphingosine-1-phosphate (S1P) has been implied to be an essential protein regarding beneficial HDL effects. In this study, we analyzed anti-inflammatory HDL properties in patients with atrial fibrillation (AF), a disease involving atrial inflammation, compared to non-AF controls and whether anti-inflammatory properties improve upon catheter ablation. Additionally, association with serum concentrations of MPO and S1P were assessed. We isolated HDL from 25 AF patients, 13 non-AF individuals and 14 AF patients at follow-up (FU) after catheter ablation. S1P was measured in a cohort of 141 AF and 21 FU patients. Following preincubation with HDL from either group, bovine aortic endothelial cells were stimulated using tumor necrosis factor α and expression of pro-inflammatory genes intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), E-selectin (SELE) and P-selectin (SELP) was assessed using qPCR. Concentrations of circulating protein of these genes as well as MPO and S1P were measured in serum samples. Compared to non-AF individuals HDL from AF patients suppressed gene expression of the pro-inflammatory adhesion molecules ICAM1, VCAM1, SELE and SELP 27%, 18%, 21% and 57% less, respectively (p < 0.05 for all except SELE p = 0.06). In FU patients, the anti-inflammatory HDL activity was improved (suppression of ICAM1 + 22%, VCAM1 + 10%, SELE + 38% and SELP + 75%, p < 0.05 for all except VCAM1 p = 0.08). AF patients using angiotensin converting enzyme inhibitors or angiotensin receptor blockers had better anti-inflammatory HDL properties than non-users (gene expression suppression at least 28% more, p < 0.05 for all except ICAM1 p = 0.051). Circulating protein concentrations were not correlated with in vitro gene-expression, but circulating P-selectin was generally elevated in AF and FU patients compared to non-AF patients. MPO plasma concentration was positively associated with gene-expression of ICAM1, VCAM1 and SELP (r2 > 0.4, p < 0.05). Serum concentrations of S1P were increased in FU patients {1.201 µM [1.077–1.543]} compared to AF patients {0.953 µM [0.807–1.135], p < 0.01} but not correlated with ICAM1, VCAM1 and SELP gene expression. We conclude that the anti-inflammatory activity of HDL is impaired in AF patients, which might promote AF progression and AF-associated complications.

show abstract

Section: Possible Mechanisms Of Hdl Impairmentsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory HDL effects are impaired in atrial fibrillation

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Myeloperoxidase (MPO) is a crucial regulator of modulating MMP activity and strongly linked to the oxidative stress and inflammation process of remodelling in atria 2 . Studies showed that plasma MPO level was higher in AF patients than in common controls, and AF patients with high MPO levels showed an increased risk of recurrence after catheter ablation 3‐6 . Considering the important roles of oxidative stress and inflammation in the initiation and maintenance of AF, 7 it remains unclear whether MPO acts as a passive marker or as a risk factor in AF.…”

Section: Introductionmentioning

confidence: 99%

SNP rs2243828 in MPO associated with myeloperoxidase level and atrial fibrillation risk in Chinese Han population

Wang

Cheng

Wang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Previous studies shown that myeloperoxidase (MPO) level is higher in patients with atrial fibrillation (AF); however, no genetic evidence between MPO and AF risk in human population was observed. Therefore, the present study was aimed to investigate the association between rs2243828, a variant in promoter region of MPO and the risk of AF in Chinese GeneID population. The results demonstrated that the minor G allele of rs2243828 showed a significant association with AF in two independent population (GeneID‐north population with 694 AF cases and 710 controls, adjusted P‐adj = 6.25 × 10−3 with an odds ratio was 0.77, GeneID‐central population with 1106 cases and 1501 controls, P‐adj = 9.88 × 10−5 with an odds ratio was 0.75). The results also showed G allele was significantly associated with lower plasma concentration of myeloperoxidase in general population. We also observed a significant difference of odds ratio between subgroups of hypertension and non‐hypertension. Therefore, our findings identified variant in MPO associated with risk of AF and it may give strong evidence to link the inflammation with the incidence of AF.

show abstract

“…AF is often the first cardiac manifestation of the laminopathy, as in our presented patient below. In laminopathy AF is found in around 60% of patients increasing to around 90% in patients who progressed to manifest dilated cardiomyopathy [8]. On the cellular level various factors are known for promoting fibrosis [8,9].…”

mentioning

confidence: 99%

“…In laminopathy AF is found in around 60% of patients increasing to around 90% in patients who progressed to manifest dilated cardiomyopathy [8]. On the cellular level various factors are known for promoting fibrosis [8,9]. In laminopathies mutations in lamin A/C lead to structural remodeling and fibrosis of the conduction system and the myocardium.…”

mentioning

confidence: 99%