Congestive heart failure: where homeostasis begets dyshomeostasis.
Despite today's standard of care, aimed at preventing homeostatic neurohormonal activation, one in every five patients recently hospitalized with congestive heart failure (CHF) will be readmitted within 30 days of discharge because of a recurrence of their symptoms and signs. In light of recent pathophysiological insights, it is now propitious to revisit CHF with a view toward complementary and evolving management strategies. CHF is a progressive systemic illness. Its features include: oxidative stress in diverse tissues; an immunostimulatory state with circulating proinflammatory cytokines; a wasting of soft tissues; and a resorption of bone. Its origins are rooted in homeostatic mechanisms gone awry to beget dyshomeostasis. For example, marked excretory losses of Ca2+ and Mg2+ accompany renin-angiotensin-aldosterone system activation, causing ionized hypocalcemia and hypomagnesemia that lead to secondary hyperparathyroidism with consequent bone resorption and a propensity to atraumatic fractures. Parathyroid hormone accounts for paradoxical intracellular Ca2+ overloading in diverse tissues and consequent systemic induction of oxidative stress. In cardiac myocytes and mitochondria, these events orchestrate opening of the mitochondrial permeability transition pore with an ensuing osmotic-based destruction of these organelles and resultant cardiomyocyte necrosis with myocardial scarring. Contemporaneous with Ca2+ and Mg2+ dyshomeostasis is hypozincemia and hyposelenemia, which compromise metalloenzyme-based antioxidant defenses, whereas hypovitaminosis D threatens Ca2+ stores needed to prevent secondary hyperparathyroidism. An intrinsically coupled dyshomeostasis of intracellular Ca2+ and Zn2+, representing pro-oxidant and antioxidant, respectively, is integral to regulating the mitochondrial redox state; it can be uncoupled by a Zn2+ supplement in favor of antioxidant defenses. Hence, the complementary use of nutriceuticals to nullify dyshomeostatic responses involving macro- and micronutrients should be considered. Evolving strategies with mitochondria-targeted interventions interfering with their uptake of Ca2+ or serving as selective antioxidant or mitochondrial permeability transition pore inhibitor may also prove efficacious in the overall management of CHF.
Kamalov
German
G
Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Bhattacharya
Syamal K
SK
Weber
Karl T
KT
D000450:Aldosterone / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D019587:Dietary Supplements; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D006706:Homeostasis; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism / Q000503:physiopathology; D008903:Minerals / Q000627:therapeutic use; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress; D010281:Parathyroid Hormone / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
D008903:Minerals; D010281:Parathyroid Hormone; D000450:Aldosterone; D015032:Zinc; D002118:Calcium