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  1. Article ; Online: Patterns of left ventricular remodeling post-myocardial infarction, determinants, and outcome.

    Logeart, Damien / Taille, Yoann / Derumeaux, Geneviève / Gellen, Barnabas / Sirol, Marc / Galinier, Michel / Roubille, François / Georges, Jean-Louis / Trochu, Jean-Noël / Launay, Jean-Marie / Vodovar, Nicolas / Bauters, Christophe / Vicaut, Eric / Mercadier, Jean-Jacques

    Clinical research in cardiology : official journal of the German Cardiac Society

    2024  

    Abstract: Aim: Left ventricular remodeling (LVR) after myocardial infarction (MI) can lead to heart failure, arrhythmia, and death. We aim to describe adverse LVR patterns at 6 months post-MI and their relationships with subsequent outcomes and to determine ... ...

    Abstract Aim: Left ventricular remodeling (LVR) after myocardial infarction (MI) can lead to heart failure, arrhythmia, and death. We aim to describe adverse LVR patterns at 6 months post-MI and their relationships with subsequent outcomes and to determine baseline.
    Methods and results: A multicenter cohort of 410 patients (median age 57 years, 87% male) with reperfused MI and at least 3 akinetic LV segments on admission was analyzed. All patients had transthoracic echocardiography performed 4 days and 6 months post-MI, and 214 also had cardiac magnetic resonance imaging performed on day 4. To predict LVR, machine learning methods were employed in order to handle many variables, some of which may have complex interactions. Six months post-MI, echocardiographic increases in LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were 14.1% [interquartile range 0.0, 32.0], 5.0% [- 14.0, 25.8], and 8.7% [0.0, 19.4], respectively. At 6 months, ≥ 15% or 20% increases in LVEDV were observed in 49% and 42% of patients, respectively, and 37% had an LVEF < 50%. The rate of death or new-onset HF at the end of 5-year follow-up was 8.8%. Baseline variables associated with adverse LVR were determined best by random forest analysis and included stroke volume, stroke work, necrosis size, LVEDV, LVEF, and LV afterload, the latter assessed by Ea or Ea/Ees. In contrast, baseline clinical and biological characteristics were poorly predictive of LVR. After adjustment for predictive baseline variables, LV dilation > 20% and 6-month LVEF < 50% were significantly associated with the risk of death and/or heart failure: hazard ratio (HR) 2.12 (95% confidence interval (CI) 1.05-4.43; p = 0.04) and HR 2.68 (95% CI 1.20-6.00; p = 0.016) respectively.
    Conclusion: Despite early reperfusion and cardioprotective therapy, adverse LVR remains frequent after acute MI and is associated with a risk of death and HF. A machine learning approach identified and prioritized early variables that are associated with adverse LVR and which were mainly hemodynamic, combining LV volumes, estimates of systolic function, and afterload.
    Language English
    Publishing date 2024-01-23
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2213295-8
    ISSN 1861-0692 ; 1861-0684
    ISSN (online) 1861-0692
    ISSN 1861-0684
    DOI 10.1007/s00392-023-02331-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Dual effect of cardiac FKBP12.6 overexpression on excitation-contraction coupling and the incidence of ventricular arrhythmia depending on its expression level.

    Gandon-Renard, Marine / Val-Blasco, Almudena / Oughlis, Célia / Gerbaud, Pascale / Lefebvre, Florence / Gomez, Susana / Journé, Clément / Courilleau, Delphine / Mercier-Nomé, Françoise / Pereira, Laetitia / Benitah, Jean-Pierre / Gómez, Ana Maria / Mercadier, Jean-Jacques

    Journal of molecular and cellular cardiology

    2024  Volume 188, Page(s) 15–29

    Abstract: FKBP12.6, a binding protein to the immunosuppressant FK506, which also binds the ryanodine receptor (RyR2) in the heart, has been proposed to regulate RyR2 function and to have antiarrhythmic properties. However, the level of FKBP12.6 expression in ... ...

    Abstract FKBP12.6, a binding protein to the immunosuppressant FK506, which also binds the ryanodine receptor (RyR2) in the heart, has been proposed to regulate RyR2 function and to have antiarrhythmic properties. However, the level of FKBP12.6 expression in normal hearts remains elusive and some controversies still persist regarding its effects, both in basal conditions and during β-adrenergic stimulation. We quantified FKBP12.6 in the left ventricles (LV) of WT (wild-type) mice and in two novel transgenic models expressing distinct levels of FKBP12.6, using a custom-made specific anti-FKBP12.6 antibody and a recombinant protein. FKBP12.6 level in WT LV was very low (0.16 ± 0.02 nmol/g of LV), indicating that <15% RyR2 monomers are bound to the protein. Mice with 14.1 ± 0.2 nmol of FKBP12.6 per g of LV (TG1) had mild cardiac hypertrophy and normal function and were protected against epinephrine/caffeine-evoked arrhythmias. The ventricular myocytes showed higher [Ca
    MeSH term(s) Animals ; Mice ; Adrenergic Agents ; Anti-Arrhythmia Agents/pharmacology ; Cardiomegaly ; Incidence ; Myocytes, Cardiac ; Ryanodine Receptor Calcium Release Channel ; Tachycardia, Ventricular/genetics ; Tacrolimus Binding Proteins
    Chemical Substances Adrenergic Agents ; Anti-Arrhythmia Agents ; Ryanodine Receptor Calcium Release Channel ; tacrolimus binding protein 1B (EC 5.2.1.-) ; Tacrolimus Binding Proteins (EC 5.2.1.-)
    Language English
    Publishing date 2024-01-14
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80157-4
    ISSN 1095-8584 ; 0022-2828
    ISSN (online) 1095-8584
    ISSN 0022-2828
    DOI 10.1016/j.yjmcc.2024.01.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: RyR2 and Calcium Release in Heart Failure.

    Benitah, Jean-Pierre / Perrier, Romain / Mercadier, Jean-Jacques / Pereira, Laetitia / Gómez, Ana M

    Frontiers in physiology

    2021  Volume 12, Page(s) 734210

    Abstract: Heart Failure (HF) is defined as the inability of the heart to efficiently pump out enough blood to maintain the body's needs, first at exercise and then also at rest. Alterations in ... ...

    Abstract Heart Failure (HF) is defined as the inability of the heart to efficiently pump out enough blood to maintain the body's needs, first at exercise and then also at rest. Alterations in Ca
    Language English
    Publishing date 2021-10-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2021.734210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Approches physiopathologiques actuelles de l'insuffisance cardiaque.

    Mercadier, Jean-Jacques

    Presse medicale (Paris, France : 1983)

    2007  Volume 36, Issue 6 Pt 2, Page(s) 979–984

    Abstract: Heart failure is the consequence of cardiac remodeling that affects all the structural and functional aspects of the heart, from its ventricular geometry to the molecular components of myocytes and other myocardial cells. This remodeling is activated by ... ...

    Title translation Current pathophysiologic approaches to heart failure.
    Abstract Heart failure is the consequence of cardiac remodeling that affects all the structural and functional aspects of the heart, from its ventricular geometry to the molecular components of myocytes and other myocardial cells. This remodeling is activated by biomechanical stress from the onset of the causal disease (sudden in cases of myocardial infarction and more progressively in cases of hypertension, for example). This biomechanical stress combines, depending on the cause, diverse degrees of diastolic stretching and systolic overload of the ventricles with systemic and tissular neurohormonal modifications. These mechanical and neurohormonal factors activate numerous intracellular signaling pathways, interconnected in a complex web, and lead to reprogramming the genome of the myocytes and other myocardial cells. Activation of some of these pathways leads to a beneficial adaptive remodeling (growth, cardiac hypertrophy of pregnancy and of athletes) or on the contrary to harmful remodeling (heart disease). The predominance of the stimulation of the harmful pathways over that of the beneficial pathways in heart disease is responsible for progression towards heart failure. Current research aims at identifying new pathways and participants in the beneficial and harmful remodeling of the myocardium in order to develop new drugs that will block ever more specifically the harmful pathways but also stimulate the beneficial ones, to prevent progression towards heart failure.
    MeSH term(s) Cardiomyopathies/physiopathology ; Heart Failure/physiopathology ; Humans ; Signal Transduction/physiology ; Ventricular Remodeling/physiology
    Language French
    Publishing date 2007-06
    Publishing country France
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 120943-7
    ISSN 2213-0276 ; 0755-4982 ; 0032-7867 ; 0301-1518
    ISSN (online) 2213-0276
    ISSN 0755-4982 ; 0032-7867 ; 0301-1518
    DOI 10.1016/j.lpm.2007.02.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Prévention cardiovasculaire: de la plaque au remodelage.

    Mercadier, Jean-Jacques

    Medecine sciences : M/S

    2004  Volume 20, Issue 6-7, Page(s) 613–614

    Title translation Cardiovascular disease prevention: from plaque to remodelling.
    MeSH term(s) Cardiovascular Diseases/etiology ; Cardiovascular Diseases/prevention & control ; Humans
    Language French
    Publishing date 2004-06
    Publishing country France
    Document type Editorial
    ZDB-ID 632733-3
    ISSN 1958-5381 ; 0767-0974
    ISSN (online) 1958-5381
    ISSN 0767-0974
    DOI 10.1051/medsci/2004206-7613
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Une seconde enzyme de conversion de l'angiotensine juste pour le coeur?

    Mercadier, Jean-Jacques

    Medecine sciences : M/S

    2003  Volume 19, Issue 2, Page(s) 141–143

    Title translation A second angiotensin-converting enzyme for the heart?.
    MeSH term(s) Blood Pressure ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/prevention & control ; Cardiovascular Physiological Phenomena ; Humans ; Peptidyl-Dipeptidase A/pharmacology ; Renin-Angiotensin System/physiology
    Chemical Substances Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Language French
    Publishing date 2003-02
    Publishing country France
    Document type News
    ZDB-ID 632733-3
    ISSN 1958-5381 ; 0767-0974
    ISSN (online) 1958-5381
    ISSN 0767-0974
    DOI 10.1051/medsci/2003192141
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Novel Cardiokine GDF3 Predicts Adverse Fibrotic Remodeling After Myocardial Infarction.

    Masurkar, Nihar / Bouvet, Marion / Logeart, Damien / Jouve, Charlène / Dramé, Fatou / Claude, Olivier / Roux, Maguelonne / Delacroix, Clément / Bergerot, Damien / Mercadier, Jean-Jacques / Sirol, Marc / Gellen, Barnabas / Livrozet, Marine / Fayol, Antoine / Robidel, Estelle / Trégouët, David-Alexandre / Marazzi, Giovanna / Sassoon, David / Valente, Mariana /
    Hulot, Jean-Sébastien

    Circulation

    2022  Volume 147, Issue 6, Page(s) 498–511

    Abstract: Background: Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery by promoting the development of ... ...

    Abstract Background: Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery by promoting the development of noncontractile fibrotic areas. The mechanisms that lead to cardiac fibrosis are diverse and incompletely characterized. We explored whether the expansion of cardiac fibroblasts after MI can be regulated through a paracrine action of cardiac stromal cells.
    Methods: We performed a bioinformatic secretome analysis of cardiac stromal PW1
    Results: Cardiac stromal PW1
    Conclusions: Our findings define a mechanism for the profibrotic action of cardiac stromal cells through secreted cardiokines, such as GDF3, a candidate marker of adverse fibrotic remodeling after MI.
    Registration: URL: https://www.
    Clinicaltrials: gov; Unique identifier: NCT01113268.
    MeSH term(s) Animals ; Humans ; Mice ; Cicatrix/pathology ; Culture Media, Conditioned/pharmacology ; Culture Media, Conditioned/metabolism ; Disease Models, Animal ; Fibrosis ; Growth Differentiation Factor 3/metabolism ; Myocardial Infarction ; Myocardium/metabolism ; Stroke Volume ; Transforming Growth Factor beta/metabolism ; Ventricular Function, Left ; Ventricular Remodeling
    Chemical Substances Culture Media, Conditioned ; Growth Differentiation Factor 3 ; Transforming Growth Factor beta ; GDF3 protein, human ; Gdf3 protein, mouse
    Language English
    Publishing date 2022-12-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.121.056272
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: VEGF-A plasma levels are associated with microvascular obstruction in patients with ST-segment elevation myocardial infarction.

    Garcia, Rodrigue / Bouleti, Claire / Sirol, Marc / Logeart, Damien / Monnot, Catherine / Ardidie-Robouant, Corinne / Caligiuri, Giuseppina / Mercadier, Jean-Jacques / Germain, Stéphane

    International journal of cardiology

    2019  Volume 291, Page(s) 19–24

    Abstract: Background: Microvascular obstruction (MVO) is associated with poor outcome after ST-segment elevation myocardial infarction (STEMI). Vascular endothelial growth factor-A (VEGF-A) is a vascular permeability inducer playing a key role in MVO pathogenesis. ...

    Abstract Background: Microvascular obstruction (MVO) is associated with poor outcome after ST-segment elevation myocardial infarction (STEMI). Vascular endothelial growth factor-A (VEGF-A) is a vascular permeability inducer playing a key role in MVO pathogenesis. We aimed to assess whether VEGF-A levels are associated with MVO, when evaluated by magnetic resonance imaging (MRI) in STEMI patients.
    Methods: The multicenter prospective PREGICA study included a CMR substudy with all consecutive patients with a first STEMI who had undergone cardiac MRI at baseline and at 6-month follow-up. Patients with initial TIMI flow >1 were excluded. VEGF-A levels were measured in blood samples drawn at inclusion.
    Results: Between 2010 and 2017, 147 patients (mean age 57 ± 10 years; 84% males) were included. MVO was present in 65 (44%) patients. After multivariate analysis, higher troponin peak (OR 1.005; 95% CI 1.001-1.008; p = 0.007) and VEGF-A levels (OR 1.003; 95% CI 1.001-1.005; p = 0.015) were independently associated with MVO. When considering only patients with successful percutaneous coronary intervention (final TIMI flow 3, n = 130), higher troponin peak (p = 0.004) and VEGF-A levels (p = 0.03) remained independently predictive of MVO. Moreover, MVO was associated with adverse left ventricular (LV) remodeling and VEGF-A levels were significantly and inversely correlated with LV ejection fraction (EF) at 6-month follow-up.
    Conclusion: Our results show that VEGF-A levels were independently associated with MVO during STEMI and correlated with mid-term LVEF alteration. VEGF-A could therefore be considered as a biomarker of MVO in STEMI patients and be used to stratify patient prognosis.
    MeSH term(s) Aged ; Biomarkers/blood ; Coronary Occlusion/blood ; Coronary Occlusion/diagnostic imaging ; Coronary Occlusion/surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Microcirculation/physiology ; Middle Aged ; Percutaneous Coronary Intervention/methods ; Prospective Studies ; ST Elevation Myocardial Infarction/blood ; ST Elevation Myocardial Infarction/diagnostic imaging ; ST Elevation Myocardial Infarction/surgery ; Vascular Endothelial Growth Factor A/blood
    Chemical Substances Biomarkers ; VEGFA protein, human ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2019-03-06
    Publishing country Netherlands
    Document type Clinical Trial ; Journal Article ; Multicenter Study
    ZDB-ID 779519-1
    ISSN 1874-1754 ; 0167-5273
    ISSN (online) 1874-1754
    ISSN 0167-5273
    DOI 10.1016/j.ijcard.2019.02.067
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  9. Article ; Online: Timing of Cardiac Magnetic Resonance Imaging Impacts on the Detection Rate of Left Ventricular Thrombus After Myocardial Infarction.

    Gellen, Barnabas / Biere, Loïc / Logeart, Damien / Lairez, Olivier / Vicaut, Eric / Furber, Alain / Mercadier, Jean-Jacques / Sirol, Marc

    JACC. Cardiovascular imaging

    2017  Volume 10, Issue 11, Page(s) 1404–1405

    MeSH term(s) Aged ; Anterior Wall Myocardial Infarction/complications ; Anterior Wall Myocardial Infarction/diagnostic imaging ; Female ; France ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Risk Factors ; ST Elevation Myocardial Infarction/complications ; ST Elevation Myocardial Infarction/diagnostic imaging ; Thrombosis/diagnostic imaging ; Thrombosis/etiology ; Time Factors
    Language English
    Publishing date 2017-02-15
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 2491503-8
    ISSN 1876-7591 ; 1936-878X
    ISSN (online) 1876-7591
    ISSN 1936-878X
    DOI 10.1016/j.jcmg.2016.12.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Gender-specific potential inhibitory role of Ca2+/calmodulin dependent protein kinase phosphatase (CaMKP) in pressure-overloaded mouse heart.

    Prévilon, Miresta / Pezet, Mylène / Vinet, Laurent / Mercadier, Jean-Jacques / Rouet-Benzineb, Patricia

    PloS one

    2014  Volume 9, Issue 6, Page(s) e90822

    Abstract: Background: Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP) has been proposed as a potent regulator of multifunctional Ca2+/calmodulin-dependent protein kinases (i.e., CaMKII). The CaMKII-dependent activation of myocyte enhancer factor 2 ( ... ...

    Abstract Background: Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP) has been proposed as a potent regulator of multifunctional Ca2+/calmodulin-dependent protein kinases (i.e., CaMKII). The CaMKII-dependent activation of myocyte enhancer factor 2 (MEF2) disrupts interactions between MEF2-histone deacetylases (HDACs), thereby de-repressing downstream gene transcription. Whether CaMKP modulates the CaMKII- MEF2 pathway in the heart is unknown. Here, we investigated the molecular and functional consequences of left ventricular (LV) pressure overload in the mouse of both genders, and in particular we evaluated the expression levels and localization of CaMKP and its association with CaMKII-MEF2 signaling.
    Methodology and principal findings: Five week-old B6D1/F1 mice of both genders underwent a sham-operation or thoracic aortic constriction (TAC). Thirty days later, TAC was associated with pathological LV hypertrophy characterized by systolic and diastolic dysfunction. Gene expression was assessed by real-time PCR. Fetal gene program re-expression comprised increased RNA levels of brain natriuretic peptide and alpha-skeletal actin. Mouse hearts of both genders expressed both CaMKP transcript and protein. Activation of signalling pathways was studied by Western blot in LV lysates or subcellular fractions (nuclear and cytoplasmic). TAC was associated with increased CaMKP expression in male LVs whereas it tended to be decreased in females. The DNA binding activity of MEF2 was determined by spectrophotometry. CaMKP compartmentalization differed according to gender. In male TAC mice, nuclear CaMKP was associated with inactive CaMKII resulting in less MEF2 activation. In female TAC mice, active CaMKII (phospho-CaMKII) detected in the nuclear fraction, was associated with a strong MEF2 transcription factor-binding activity.
    Conclusions/significance: Gender-specific CaMKP compartmentalization is associated with CaMKII-mediated MEF2 activation in pressure-overloaded hearts. Therefore, CaMKP could be considered as an important novel cellular target for the development of new therapeutic strategies for heart diseases.
    MeSH term(s) Animals ; Cardiomegaly/enzymology ; Female ; Hypertension/enzymology ; MEF2 Transcription Factors/metabolism ; Male ; Mice ; Myocardium/enzymology ; Phosphoprotein Phosphatases/physiology ; Sex Characteristics ; Ventricular Remodeling
    Chemical Substances MEF2 Transcription Factors ; calmodulin dependent protein kinase II phosphatase (EC 3.1.3.-) ; Phosphoprotein Phosphatases (EC 3.1.3.16)
    Language English
    Publishing date 2014-03-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0090822
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