Advertisement
Canadian Journal of Cardiology
Advanced searchSave search
Editorial|Articles in Press

Mineralocorticoid receptor on T cells contributes to injury and remodeling of ischemic myocardium

  • Ernesto L. Schiffrin
    Correspondence
    Corresponding Author: Ernesto L. Schiffrin, C.M., MD, PhD, FRSC, FRCPC, FACP, , Address: Department of Medicine, #B-127, SMBD-Jewish General Hospital, 3755 Côte-Ste-Catherine Rd., Montreal, QC, Canada H3T 1E2, Ph: 514-340-7538, Fax: 514-340-7539
    Affiliations
    Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research and Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada
    Search for articles by this author
Published:February 10, 2023DOI:https://doi.org/10.1016/j.cjca.2023.02.007
Mineralocorticoid receptor on T cells contributes to injury and remodeling of ischemic myocardium
Previous ArticleCombined use of NoblestitchTM EL system and Amplatzer device to close a patent foramen ovale with complex anatomy
Next ArticleRespiratory function assessment in patients with atrial fibrillation: A needed extension of combined comorbidity management?
      Aldosterone has been characterized by its actions on the kidney via the mineralocorticoid receptor (MR) to control sodium excretion, and thus regulate sodium and volume homeostasis and blood pressure. However, aldosterone acts as well on the heart and blood vessels to exert physiological and pathophysiological actions.
      • Ferrario C.M.
      • Schiffrin E.L.
      Translational Success Stories: Role of Mineralocorticoid Receptor Antagonists in Cardiovascular Disease.
      Circ Res. 2015; 116: 206-213
      Excess aldosterone in relation to salt status acting through MR via both genomic and nongenomic effects contributes to endothelial dysfunction and stiffness, and vascular and cardiorenal adverse remodeling, and thus participates in the target organ damage associated with hypertension, heart failure, myocardial infarction, and chronic kidney disease.
      • Briet M.
      • Schiffrin E.L.
      Aldosterone effects on the kidney and cardiovascular system, and clinical value of aldosterone antagonism.
      Nature Reviews Nephrology. 2010; 6: 261-273
      In all these conditions, blockade of the MR has been shown to exert beneficial cardiorenal actions that improve outcomes of patients.
      • Williams B.
      • MacDonald T.M.
      • Morant S.
      • Webb D.J.
      • Sever P.
      • McInnes G.
      • Ford I.
      • Cruickshank J.K.
      • Caulfield M.J.
      • Salsbury J.
      • Mackenzie I.
      • Padmanabhan S.
      • Brown M.J.
      for The British Hypertension Society’s PATHWAY Studies Group.
      Lancet. 2015; 386: 2059-2068
      , 
      • Pitt B.
      • Zannad F.
      • Remme W.J.
      • Cody R.
      • Castaigne A.
      • Perez A.
      • Palensky J.
      • Wittes J.
      for the Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure.
      N Engl J Med. 1999; 341: 709-717
      , 
      • Pitt B.
      • Remme W.
      • Zannad F.
      • Neaton J.
      • Martinez F.
      • Roniker B.
      • Bittman R.
      • Hurley S.
      • Kleiman J.
      • Gatlin M.
      for the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction.
      N Engl J Med. 2003; 348: 1309-1321
      , 
      • Bakris G.L.
      • Agarwal R.
      • Anker S.D.
      • Pitt B.
      • Ruilope L.M.
      • Rossing P.
      • Kolkhof P.
      • Nowack C.
      • Schloemer P.
      • Joseph A.
      • Filippatos G.
      for the FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes.
      N Engl J Med. 2020; 383: 2219-2229
      Furthermore, deletion of cardiomyocyte mineralocorticoid receptor ameliorates adverse remodeling after myocardial infarction, demonstrating in experimental myocardial infarction the role of the MR in cardiac remodeling following cardiomyocyte ischemia.
      • Fraccarollo D.
      • Berger S.
      • Galuppo P.
      • Kneitz S.
      • Hein L.
      • Schu¨tz G.
      • Frantz S.
      • Ertl G.
      • Bauersachs J.
      Deletion of cardiomyocyte mineralocorticoid receptor ameliorates adverse remodeling after myocardial infarction.
      Circulation. 2011; 123: 400-408
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Ferrario C.M.
        • Schiffrin E.L.
        Translational Success Stories: Role of Mineralocorticoid Receptor Antagonists in Cardiovascular Disease.
        Circ Res. 2015; 116: 206-213
        View in Article
        • Briet M.
        • Schiffrin E.L.
        Aldosterone effects on the kidney and cardiovascular system, and clinical value of aldosterone antagonism.
        Nature Reviews Nephrology. 2010; 6: 261-273
        View in Article
        • Williams B.
        • MacDonald T.M.
        • Morant S.
        • Webb D.J.
        • Sever P.
        • McInnes G.
        • Ford I.
        • Cruickshank J.K.
        • Caulfield M.J.
        • Salsbury J.
        • Mackenzie I.
        • Padmanabhan S.
        • Brown M.J.
        for The British Hypertension Society’s PATHWAY Studies Group.
        Lancet. 2015; 386: 2059-2068
        View in Article
        • Pitt B.
        • Zannad F.
        • Remme W.J.
        • Cody R.
        • Castaigne A.
        • Perez A.
        • Palensky J.
        • Wittes J.
        for the Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure.
        N Engl J Med. 1999; 341: 709-717
        View in Article
        • Pitt B.
        • Remme W.
        • Zannad F.
        • Neaton J.
        • Martinez F.
        • Roniker B.
        • Bittman R.
        • Hurley S.
        • Kleiman J.
        • Gatlin M.
        for the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction.
        N Engl J Med. 2003; 348: 1309-1321
        View in Article
        • Bakris G.L.
        • Agarwal R.
        • Anker S.D.
        • Pitt B.
        • Ruilope L.M.
        • Rossing P.
        • Kolkhof P.
        • Nowack C.
        • Schloemer P.
        • Joseph A.
        • Filippatos G.
        for the FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes.
        N Engl J Med. 2020; 383: 2219-2229
        View in Article
        • Fraccarollo D.
        • Berger S.
        • Galuppo P.
        • Kneitz S.
        • Hein L.
        • Schu¨tz G.
        • Frantz S.
        • Ertl G.
        • Bauersachs J.
        Deletion of cardiomyocyte mineralocorticoid receptor ameliorates adverse remodeling after myocardial infarction.
        Circulation. 2011; 123: 400-408
        View in Article
        • Bene N.C.
        • Alcaide P.
        • Wortis H.H.
        • Jaffe I.Z.
        Mineralocorticoid receptors in immune cells: emerging role in cardiovascular disease.
        Steroids. 2014; 91: 38-45
        View in Article
        • Rickard A.J.
        • Morgan J.
        • Tesch G.
        • Funder J.W.
        • Fuller P.J.
        • Young M.J.
        Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure.
        Hypertension. 2009; 54: 537-543
        View in Article
        • Usher M.G.
        • Duan S.Z.
        • Ivaschenko C.Y.
        • Frieler R.A.
        • Berger S.
        • Schu¨tz G.
        • Lumeng C.N.
        • Mortensen R.M.
        Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice.
        J Clin Invest. 2010; 120: 3350-3364
        View in Article
        • Wang Y.-L.
        • Ma X.-X.
        • Zhu H.
        • Bai L.
        • Du L.J.
        • Zhu S.W.
        • Pan Y.-T.
        • Lin W.-Z.
        • Liu Y.
        • Liu Y.
        • Zhang W.-W.
        • Hou X.-M.
        • Li R.-G.
        • Duan S.-Z.
        T cell Mineralocorticoid Receptor Deficiency 1 Attenuates Pathological Ventricular Remodeling After Myocardial Infarction.
        Can J Cardiol. 2023; (in press)
        View in Article
        • Li C.
        • Sun X.N.
        • Zeng M.R.
        • Zheng X.J.
        • Zhang Y.Y.
        • Wan Q.
        • Zhang W.C.
        • Shi C.
        • Du L.J.
        • Ai T.J.
        • Liu Y.
        • Liu Y.
        • Du L.L.
        • Yi Y.
        • Yu Y.
        • Duan S.Z.
        Mineralocorticoid Receptor Deficiency in T Cells Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction Through Modulating T-Cell Activation.
        Hypertension. 2017; 70: 137-147
        View in Article
        • Sun X.N.
        • Li C.
        • Liu Y.
        • Du L.J.
        • Zeng M.R.
        • Zheng X.J.
        • Zhang W.C.
        • Liu Y.
        • Zhu M.
        • Kong D.
        • Zhou L.
        • Lu L.
        • Shen Z.X.
        • Yi Y.
        • Du L.
        • Qin M.
        • Liu X.
        • Hua Z.
        • Sun S.
        • Yin H.
        • Zhou B.
        • Yu Y.
        • Zhang Z.
        • Duan S.Z.
        T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma.
        Circ Res. 2017; 120: 1584-1597
        View in Article
        • Silvestre J.S.
        • Heymes C.
        • Oubénaïssa A.
        • Robert V.
        • Aupetit-Faisant B.
        • Carayon A.
        • Swynghedauw B.
        • Delcayre C.
        Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis.
        Circulation. 1999; 99: 2694-2701
        View in Article
        • Caillon A.
        • Paradis P.
        • Schiffrin E.L.
        Role of immune cells in hypertension.
        Brit J Pharmacol. 2019; 176: 1818-1828
        View in Article

      Article info

      Publication history

      Accepted: February 8, 2023
      Received: February 2, 2023

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      URL: ladydavis.ca/en/ernestoschiffrin

      Identification

      DOI: https://doi.org/10.1016/j.cjca.2023.02.007

      Copyright

      © 2023 Published by Elsevier Inc. on behalf of the Canadian Cardiovascular Society.

      ScienceDirect

      Access this article on ScienceDirect

      Linked Article

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX