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  1. Artikel ; Online: Neutrophils and Circulating Inflammatory Biomarkers in Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction.

    Chaar, Diana / Dumont, Benjamin L / Vulesevic, Branka / Neagoe, Paul-Eduard / Räkel, Agnès / White, Michel / Sirois, Martin G

    The American journal of cardiology

    2022  Band 178, Seite(n) 80–88

    Abstract: Heart failure with preserved ejection fraction (HFpEF) is characterized by low-grade chronic inflammation, which could be exacerbated by type 2 diabetes mellitus (DM). We hypothesized that neutrophils in patients with DM and patients with HFpEF with/ ... ...

    Abstract Heart failure with preserved ejection fraction (HFpEF) is characterized by low-grade chronic inflammation, which could be exacerbated by type 2 diabetes mellitus (DM). We hypothesized that neutrophils in patients with DM and patients with HFpEF with/without DM contribute to low-grade inflammation through the release of pro-inflammatory cytokines. Venous blood was withdrawn from patients with DM (n = 22), HFpEF (n = 15), HFpEF with DM (n = 13), and healthy controls (CTL) (n = 21). Levels of circulating cytokines and in vitro cytokines released by isolated neutrophils were assessed by enzyme-linked immunosorbent assay. Compared with CTL, there was a significant decrease in circulating nitric oxide in patients with DM (p ≤0.001), HFpEF (p ≤0.05), and HFpEF with DM (p ≤0.001) up to 44%. Circulating soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels increased (up to 2.5-fold and 1.9-fold, respectively; p ≤0.001) in patients with HFpEF and patients with HFpEF and DM, whereas soluble E-selectin only increased in patients with HFpEF and DM (1.4-fold, p ≤0.001). Circulating vascular endothelial growth factor levels were similar in CTL and patients with DM but were decreased in patients with HFpEF with/without DM (up to 94%; p ≤0.001). Circulating C-reactive protein, interleukin (IL)-8, IL-6, and IL-receptor antagonist increased in all patient groups with a maximum of 3.3-fold, 4.7-fold, 4.8-fold, and 1.6-fold, respectively, in patients with HFpEF and patients with DM. In vitro, lipopolysaccharide increased neutrophils IL-6 release from HFpEF with DM (3.7-fold; p ≤0.001), and IL-8 release from DM and HFpEF with DM versus CTL (2.8-fold and 10.1-fold, respectively; p ≤0.001). IL-1 receptor antagonist and vascular endothelial growth factor release from HFpEF neutrophils significantly decreased up to 87.0% and 92.2%, respectively, versus CTL. Neutrophils from patients with DM and HFpEF release more cytokines than CTL. This increase in pro-inflammatory status may explain the greater event rate in patients with HFpEF and DM.
    Mesh-Begriff(e) Biomarkers ; Cytokines ; Diabetes Mellitus, Type 2/complications ; Heart Failure ; Humans ; Inflammation ; Interleukin-6 ; Neutrophils/metabolism ; Stroke Volume ; Vascular Endothelial Growth Factor A
    Chemische Substanzen Biomarkers ; Cytokines ; Interleukin-6 ; Vascular Endothelial Growth Factor A
    Sprache Englisch
    Erscheinungsdatum 2022-07-08
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80014-4
    ISSN 1879-1913 ; 0002-9149
    ISSN (online) 1879-1913
    ISSN 0002-9149
    DOI 10.1016/j.amjcard.2022.05.026
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Neutrophils pro-inflammatory and anti-inflammatory cytokine release in patients with heart failure and reduced ejection fraction.

    Chaar, Diana / Dumont, Benjamin / Vulesevic, Branka / Neagoe, Paul-Eduard / Rakel, Agnes / Sirois, Martin G / White, Michel

    ESC heart failure

    2021  Band 8, Heft 5, Seite(n) 3855–3864

    Abstract: Aims: Heart failure with reduced ejection fraction (HFrEF) is characterized by sub-clinical inflammation. Changes in selected biomarkers of inflammation concomitant with the release of pro-inflammatory and anti-inflammatory cytokines by neutrophils have ...

    Abstract Aims: Heart failure with reduced ejection fraction (HFrEF) is characterized by sub-clinical inflammation. Changes in selected biomarkers of inflammation concomitant with the release of pro-inflammatory and anti-inflammatory cytokines by neutrophils have not been investigated in patients with HFrEF.
    Methods and results: Fifty-two patients, aged 68.8 ± 1.7 years, with HFrEF and left ventricular ejection fraction 28.7 ± 1.0%, and 21 healthy controls (CTL) were recruited. Twenty-five HF patients had type 2 diabetes. Venous blood samples from HF and CTL were collected once. Neutrophil-derived pro-inflammatory and anti-inflammatory cytokine levels were assessed in plasma by ELISA. Plasma biomarkers assessed included: C-reactive protein (CRP), vascular endothelial growth factor (VEGF), interleukins (IL)-6, -8, -1 receptor antagonist (-1RA), nitric oxide (NO), soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and E-Selectin (sE-Sel). Neutrophils were isolated and stimulated with various agonists to promote VEGF, IL-6, IL-8, and IL-1RA release. Compared with CTL, HFrEF patients showed a marked decrease in circulating VEGF [178.0 (interquartile range; IQR 99.6; 239.2) vs. 16.2 (IQR 9.3; 20.2) pg/mL, P ≤ 0.001] and NO [45.2 (IQR 42.1; 57.6) vs. 40.6 (IQR 30.4; 47.1) pg/mL, P = 0.0234]. All other circulating biomarkers were significantly elevated. Neutrophils isolated from patients with HFrEF exhibited a greater IL-8 release in response to LPS [1.2 ± 0.1 (CTL); 10.4 ± 1.6 ng/mL (HFrEF) and 12.4 ± 1.6 ng/mL (HFrEF and DM), P ≤ 0.001]. IL-6 release in response to LPS was not changed in HFrEF patients without diabetes, whereas it was significantly increased in patients with HFrEF and diabetes [46.7 ± 3.9 (CTL) vs. 165.8 ± 48.0 pg/mL (HFrEF), P = 0.1713 and vs. 397.7 ± 67.4 pg/mL (HFrEF and DM), P ≤ 0.001]. In contrast, the release of VEGF and IL-1RA was significantly reduced in HFrEF (VEGF; TNF-α: 38.6 ± 3.1 and LPS: 25.3 ± 2.6 pg/mL; IL1RA; TNF-α: 0.6 ± 0.04 and LPS: 0.3 ± 0.02 ng/mL) compared with CTL (VEGF; TNF-α: 60.0 ± 9.4 and LPS: 41.2 ± 5.9 pg/mL; IL1RA; TNF-α: 3.3 ± 0.2 and LPS: 2.3 ± 0.1 ng/mL).
    Conclusions: Patients with HFrEF exhibit a significant decrease in circulating VEGF. The release of VEGF and both pro-inflammatory and anti-inflammatory cytokines from the stimulated neutrophils is markedly altered in these patients. The clinical significance of these findings deserves further investigation.
    Mesh-Begriff(e) Anti-Inflammatory Agents ; Cytokines ; Diabetes Mellitus, Type 2 ; Heart Failure ; Humans ; Neutrophils ; Stroke Volume ; Vascular Endothelial Growth Factor A ; Ventricular Function, Left
    Chemische Substanzen Anti-Inflammatory Agents ; Cytokines ; Vascular Endothelial Growth Factor A
    Sprache Englisch
    Erscheinungsdatum 2021-08-12
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2814355-3
    ISSN 2055-5822 ; 2055-5822
    ISSN (online) 2055-5822
    ISSN 2055-5822
    DOI 10.1002/ehf2.13539
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Cardiopulmonary, biomarkers, and vascular responses to acute hypoxia following cardiac transplantation.

    Sanz-de la Garza, Maria / Iannino, Nadia / Finnerty, Vincent / Mansour, Asmaa / Blondeau, Lucie / Gayda, Mathieu / Chaar, Diana / Sirois, Martin G / Racine, Normand / de Denus, Simon / Harel, François / White, Michel

    Clinical transplantation

    2018  Band 32, Heft 9, Seite(n) e13352

    Abstract: Previous studies have suggested good adaptation of cardiac transplant (CTx) recipients to exposure to a high altitude. No studies have investigated the cardiopulmonary and biomarker responses to acute hypoxic challenges following CTx. Thirty-six CTx ... ...

    Abstract Previous studies have suggested good adaptation of cardiac transplant (CTx) recipients to exposure to a high altitude. No studies have investigated the cardiopulmonary and biomarker responses to acute hypoxic challenges following CTx. Thirty-six CTx recipients and 17 age-matched healthy controls (HC) were recruited. Sixteen (16) patients (42%) had cardiac allograft vasculopathy (CAV). Cardiopulmonary responses to maximal and submaximal exercise at 21% O
    Mesh-Begriff(e) Adaptation, Physiological ; Altitude ; Biomarkers/analysis ; Cardiovascular System/physiopathology ; Case-Control Studies ; Exercise ; Female ; Follow-Up Studies ; Heart Transplantation/methods ; Humans ; Hypoxia/physiopathology ; Lung/physiology ; Male ; Middle Aged ; Oxygen Consumption ; Prospective Studies
    Chemische Substanzen Biomarkers
    Sprache Englisch
    Erscheinungsdatum 2018-08-18
    Erscheinungsland Denmark
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639001-8
    ISSN 1399-0012 ; 0902-0063
    ISSN (online) 1399-0012
    ISSN 0902-0063
    DOI 10.1111/ctr.13352
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: A comparison of the effects of selective and non-selective mineralocorticoid antagonism on glucose homeostasis of heart failure patients with glucose intolerance or type II diabetes: A randomized controlled double-blind trial.

    Korol, Sandra / White, Michel / O'Meara, Eileen / Tournoux, François / Racine, Normand / Ducharme, Anique / Rouleau, Jean-Lucien / Liszkowski, Mark / Mansour, Asmaa / Jutras, Martin / Guertin, Marie-Claude / Bernier, Mathieu / Lavoie, Joël / Leclair, Grégoire / Neagoe, Paul-Eduard / Chaar, Diana / Sirois, Martin G / de Denus, Simon

    American heart journal

    2018  Band 204, Seite(n) 190–195

    Abstract: Mineralocorticoid receptor antagonists (MRAs) decrease morbidity and mortality in patients with heart failure (HF). However, spironolactone, a non-selective MRA, has been shown to exert a harmful effect on glucose homeostasis. The objective of this ... ...

    Abstract Mineralocorticoid receptor antagonists (MRAs) decrease morbidity and mortality in patients with heart failure (HF). However, spironolactone, a non-selective MRA, has been shown to exert a harmful effect on glucose homeostasis. The objective of this multicenter, randomized, controlled, double-blind trial was to compare the effects of spironolactone to those of the selective MRA eplerenone on glucose homeostasis among 62 HF patients with glucose intolerance or type II diabetes. Trial registration number:NCT01586442.
    Mesh-Begriff(e) Aged ; Biomarkers/blood ; Biomarkers/urine ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/complications ; Double-Blind Method ; Eplerenone/adverse effects ; Eplerenone/therapeutic use ; Female ; Glucose Intolerance/complications ; Glycated Hemoglobin A/metabolism ; Heart Failure/blood ; Heart Failure/complications ; Heart Failure/drug therapy ; Heart Failure/physiopathology ; Homeostasis ; Humans ; Insulin/blood ; Insulin Resistance ; Male ; Middle Aged ; Mineralocorticoid Receptor Antagonists/adverse effects ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Prospective Studies ; Spironolactone/adverse effects ; Spironolactone/therapeutic use ; Stroke Volume
    Chemische Substanzen Biomarkers ; Blood Glucose ; Glycated Hemoglobin A ; Insulin ; Mineralocorticoid Receptor Antagonists ; hemoglobin A1c protein, human ; Spironolactone (27O7W4T232) ; Eplerenone (6995V82D0B)
    Sprache Englisch
    Erscheinungsdatum 2018-07-10
    Erscheinungsland United States
    Dokumenttyp Comparative Study ; Letter ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 80026-0
    ISSN 1097-6744 ; 0002-8703
    ISSN (online) 1097-6744
    ISSN 0002-8703
    DOI 10.1016/j.ahj.2018.07.002
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: Decreased circulating and neutrophil mediated VEGF-A165 release in stable long-term cardiac transplant recipients.

    Vitiello, Damien / Chaar, Diana / Neagoe, Paul-Eduard / Ducharme, Anique / Carrier, Michel / Pelletier, Guy B / Racine, Normand / Liszkowski, Mark / Sirois, Martin G / White, Michel

    Vascular cell

    2015  Band 7, Seite(n) 4

    Abstract: Background: Vascular endothelial growth factor (VEGF) may play a role on the allograft remodelling following cardiac transplantation (CTx). We measured the circulating levels of VEGF-A165 concomitantly with the proinflammatory (Interleukin-8; IL-8), ... ...

    Abstract Background: Vascular endothelial growth factor (VEGF) may play a role on the allograft remodelling following cardiac transplantation (CTx). We measured the circulating levels of VEGF-A165 concomitantly with the proinflammatory (Interleukin-8; IL-8), anti-inflammatory (IL-1 receptor antagonist; IL-1RA) and their release from neutrophils of CTx recipients.
    Methods: Eighteen CTx recipients aged 49.6 ± 3.1 years, being transplanted for 145 ± 20 months were age-matched to 35 healthy control (HC) subjects. Concomitantly to plasma assessment, circulating neutrophils were isolated, purified and stimulated by vehicle (PBS), N-formyl-Met-Leu-Phe (fMLP, 10(-7) M), bacterial lipopolysaccharide (LPS, 1 μg/mL), or tumour necrosis factor alpha (TNF-α, 10 ng/mL).
    Results: Compared with HC, CTx recipients exhibited a decrease (-80%) in plasmatic levels of VEGF-A165 (225 ± 42 (HC) vs 44 ± 10 pg/mL (CTx); (p < 0.001). There were no differences in the levels of IL-8 and IL-1RA. Under basal or stimulated conditions, neutrophils from CTx patients exhibited a marked decrease ranging from -30 to -88% on their capacity to release VEGF-A165, IL-8 and IL-1RA upon stimulation.
    Conclusions: Long-term CTx recipients exhibit a marked reduction in the circulating levels of VEGF-A165, as well as neutrophil-mediated release of VEGF-A165, IL-1RA and IL-8 compared to healthy volunteers. The mechanisms and physiological impacts of these findings deserve additional investigations.
    Sprache Englisch
    Erscheinungsdatum 2015
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2595417-9
    ISSN 2045-824X
    ISSN 2045-824X
    DOI 10.1186/s13221-015-0029-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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