title: Parathyroid hormone, a crucial mediator of pathologic cardiac remodeling in aldosteronism.
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 Ca(2+) and Mg(2+) that accompany aldosteronism which creates ionized hypocalcemia and hypomagnesemia, providing major stimuli to the parathyroids' enhanced secretion of PTH. Invoked to restore extracellular Ca(2+) and Mg(2+) homeostasis, elevations in plasma PTH lead to paradoxical intracellular Ca(2+) overloading of diverse tissues. In the case of cardiomyocytes, the excessive intracellular Ca(2+) 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.
authors.affiliation: Division of Cardiovascular Diseases, University of Tennessee Health Science Center, 956 Court Ave., Suite A312, Memphis, TN 38163, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rutledge
authors.forename: Victor
authors.initials: V
authors.lastname: Farah
authors.forename: Adedayo A
authors.initials: AA
authors.lastname: Adeboye
authors.forename: Michael R
authors.initials: MR
authors.lastname: Seawell
authors.forename: Syamal K
authors.initials: SK
authors.lastname: Bhattacharya
authors.forename: Karl T
authors.initials: KT
authors.lastname: Weber
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D010281:Parathyroid Hormone; D000450:Aldosterone