RESUMO
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.
Assuntos
Fibrilação Atrial , Animais , Anti-Inflamatórios , Bovinos , Células Endoteliais , Humanos , Lipoproteínas HDL , Selectina-P , Molécula 1 de Adesão de Célula VascularRESUMO
BACKGROUND: Myeloperoxidase (MPO), secreted by neutrophils under inflammatory conditions, is elevated in atrial fibrillation (AF). MPO may be involved in atrial remodeling that underpins AF progression characterized by a switch from paroxysmal to persistent AF and the formation of low-voltage areas (LVA). MPO levels are modulated by renin-angiotensin system antagonists (RAS-A), commonly used to treat AF comorbidities, and are associated with reduced AF incidence, implicating a potential link. OBJECTIVE: We investigated MPO levels in progressing AF in peripheral and left atrial (LA) blood and analyzed a potential effect of RAS-A. METHODS: Samples of AF patients were collected from the femoral vein and the LA during catheter ablation (n = 121) and at follow-up (n = 23). No-AF probands (n = 37) served as controls. MPO was determined using commercial ELISA. RESULTS: MPO levels were significantly increased in AF patients compared to controls (median, 27.7 ng/ml (IQR 14.3-66.6) versus 12.6 (IQR 9.9-17.7), p < 0.001), without differences between clinical AF progression phenotypes. MPO concentration was tenfold higher in LA than periphery (279.2 ng/ml (IQR 202.2-342.9) versus 27.7 ng/ml (IQR 14.3-65.9), p < 0.001). MPO remained increased at midterm follow-up irrespective of rhythm outcome. RAS-A was associated with significantly lower peripheral (22.2 ng/ml (IQR 12.7-48.2) versus 37.1 ng/ml (IQR 18.2-85.2), p < 0.05) MPO levels in AF patients. CONCLUSION: The pro-fibrotic enzyme MPO is generally elevated in AF patients irrespective of AF type, the presence of LVA or midterm rhythm outcome. Our data suggest that MPO may directly originate from the LA. RAS-A decrease peripheral MPO levels in AF patients.
Assuntos
Fibrilação Atrial/fisiopatologia , Ablação por Cateter , Peroxidase/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Idoso , Fibrilação Atrial/enzimologia , Remodelamento Atrial/fisiologia , Estudos de Coortes , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The human gut microbiome and its metabolite Trimethylamine N-oxide (TMAO) are sensitive to the human diet and are involved in the complex pathomechanisms that underpin diabetes, obesity, and cardiovascular diseases. A potential involvement of increased TMAO in atrial fibrillation (AF) manifestation and progression is not clear. We measured TMAO in peripheral blood of 45 AF patients and 20 non-AF individuals (matched for age, sex, BMI, prevalence of hypertension and diabetes). TMAO levels in AF (median [IQR] 3.5 µM [2.51-4.53]) were comparable with those in non-AF individuals (3.62 µM [2.49-5.46]) (p = 0.629). There was no association between TMAO and AF progression phenotypes (p = 0.588). In 35 AF patients, TMAO was additionally measured 12-18 months after AF catheter ablation. TMAO levels at baseline and follow-up were correlated (r = 0.481, p = 0.003), and TMAO was increased independent from the success (restoration of sinus rhythm) of the ablation procedure. The data of this pilot study indicate that TMAO is not generally higher in AF and is not associated with AF progression phenotypes. The observed TMAO increase 12-18 months after AF catheter ablation needs further investigation in a larger cohort.
RESUMO
BACKGROUND: Reperfusion strategies in acute myocardial infarction (AMI) may result in ischemia reperfusion injury characterized by increased oxidative stress, inflammation, and ultimately death of myocardial tissue which may be of particular importance in infarct-related cardiogenic shock (CS). Many anti-oxidative and immune regulatory processes depend on selenium which in large proportions is bound to circulating selenoprotein P (SelP). Individual SelP patterns may therefore be associated with inflammatory response and possibly mortality in patients with CS post AMI. METHODS: In the randomized Intra-Aortic Balloon Pump in cardiogenic Shock II (IABP-SHOCK II)-trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. In a predefined biomarker substudy of 147 patients, we analyzed SelP levels 1 and 3 days following randomization. Samples were compared with healthy controls and associations with the unspecific inflammatory marker C-reactive protein (CRP) were analyzed. RESULTS: Compared with controls SelP levels in patients with infarct-related CS were markedly higher (2.7-fold at day 1 and 5.7-fold at day 3 following AMI, all Pâ<â0.001). Thirty-day mortality was significantly higher in patients with SelP levels above the 75th percentile at day 3 following AMI (26% vs. 46%, Pâ=â0.045). SelP was significantly proportionally correlated with CRP 1 (Râ=â0.762, Pâ<â0.0001) and 3 days (Râ=â0.777 Pâ<â0.0001) following AMI. CONCLUSION: SelP levels are significantly increased post AMI with CS. Higher SelP levels are associated with increased CRP levels indicative for inflammatory processes. Future studies should focus on the characterization of SelP profiles following AMI and the identification of pathomechanisms affected by SelP.