Parathyroid hormone, a crucial mediator of pathologic cardiac remodeling in Aldosteronism

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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalCardiovascular Drugs and Therapy
Volume27
Issue number2
DOIs
StatePublished - Apr 1 2013

Fingerprint

Hyperaldosteronism
Parathyroid Hormone
Necrosis
Cardiac Myocytes
Secondary Hyperparathyroidism
Hypocalcemia
Aldosterone
Transducers
Organelles
Cicatrix
Permeability
Myocardium
Mitochondria
Oxidative Stress
Homeostasis
Fibrosis
Adenosine Triphosphate
Membranes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

Parathyroid hormone, a crucial mediator of pathologic cardiac remodeling in Aldosteronism. / Rutledge, Michael R.; Farah, Victor; Adeboye, Adedayo A.; Seawell, Michael R.; Bhattacharya, Syamal; Weber, Karl.

In: Cardiovascular Drugs and Therapy, Vol. 27, No. 2, 01.04.2013, p. 161-170.

Research output: Contribution to journalArticle

Rutledge, Michael R. ; Farah, Victor ; Adeboye, Adedayo A. ; Seawell, Michael R. ; Bhattacharya, Syamal ; Weber, Karl. / Parathyroid hormone, a crucial mediator of pathologic cardiac remodeling in Aldosteronism. In: Cardiovascular Drugs and Therapy. 2013 ; Vol. 27, No. 2. pp. 161-170.
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