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Parathyroid Hormone, A Crucial Mediator of Pathologic Cardiac Remodeling in Aldosteronism

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Abstract

Aldosteronism, or chronic elevation in plasma aldosterone (ALDO) (inappropriate for dietary Na+ intake), is accompanied by an adverse structural remodeling of the heart and vasculature. Herein, we bring forward a new perspective in which parathyroid hormone (PTH) is identified as a crucial mediator of pathologic cardiac remodeling in aldosteronism. Secondary hyperparathyroidism (SHPT) appears because of the marked urinary and fecal losses of Ca2+ and Mg2+ that accompany aldosteronism which creates ionized hypocalcemia and hypomagnesemia, providing major stimuli to the parathyroids' enhanced secretion of PTH. Invoked to restore extracellular Ca2+ and Mg2+ homeostasis, elevations in plasma PTH lead to paradoxical intracellular Ca2+ overloading of diverse tissues. In the case of cardiomyocytes, the excessive intracellular Ca2+ accumulation involves both cytosolic free and mitochondrial domains with a consequent induction of oxidative stress by these organelles and lost ATP synthesis. The ensuing opening of their inner membrane permeability transition pore (mPTP) accounts for the osmotic swelling and structural degeneration of mitochondria followed by programed cell necrosis. Tissue repair, invoked to preserve the structural integrity of myocardium accounts for a replacement fibrosis, or scarring, which is found scattered throughout the right and left heart; it represents a morphologic footprint of earlier necrosis. Multiple lines of evidence are reviewed that substantiate the PTH-mediated paradigm and the mitochondriocentric signal-transducer-effector pathway to cardiomyocyte necrosis.

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  1. Division of Cardiovascular Diseases, University of Tennessee Health Science Center, 956 Court Ave., Suite A312, Memphis, TN, 38163, USA

    Michael R. Rutledge, Victor Farah, Adedayo A. Adeboye, Michael R. Seawell, Syamal K. Bhattacharya & Karl T. Weber

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  1. Michael R. Rutledge
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  2. Victor Farah
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Correspondence to Karl T. Weber.

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Rutledge, M.R., Farah, V., Adeboye, A.A. et al. Parathyroid Hormone, A Crucial Mediator of Pathologic Cardiac Remodeling in Aldosteronism. Cardiovasc Drugs Ther 27, 161–170 (2013). https://doi.org/10.1007/s10557-012-6378-0

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