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

Coronary Microvascular Dysfunction Induced by Primary Hyperparathyroidism is Restored After Parathyroidectomy

“…The following variables were forced into the model one at a time, but their inclusion did not affect the relationship between coronary flow reserve Յ2.5 and PTH: sex, time from diagnosis, current smoking, history of diabetes mellitus, and use of statins or nitrates. mortality in PHPT 2 but also in secondary hyperparathyroidism (SHPT), 7,17 in which PTH is secreted by parathyroid glands, seeking to restore the dyshomeostasis of essential cations (ie, hypocalcemia and hypomagnesemia), in conditions like chronic renal failure, 18 low renin hypertension, 19 primary aldosteronism, 20 heart failure, 10,21,22 and vitamin D deficiency. 7,17,23 The latter is particularly common among women and the elderly, in whom lactose intolerance and reduced dietary Ca 2ϩ may be also contributory.…”

“…25 As a consequence, the hypothesis of specific cardiovascular actions of PTH, extending beyond the control of bone and mineral metabolism, has evolved over time and is supported by multiple lines of evidence. 1,5,17,22 Interestingly, in different tissues, PTH may exert an ionophoric effect, causing intracellular Ca 2ϩ overload and reactive oxygen species generation. 18,22,26 Indeed, impaired antioxidant defenses resulting from low intracellular zinc are often coupled to intracellular Ca 2ϩ overload and further worsen the redox imbalance, leading to severe cell injury and death.…”

“…1,5,17,22 Interestingly, in different tissues, PTH may exert an ionophoric effect, causing intracellular Ca 2ϩ overload and reactive oxygen species generation. 18,22,26 Indeed, impaired antioxidant defenses resulting from low intracellular zinc are often coupled to intracellular Ca 2ϩ overload and further worsen the redox imbalance, leading to severe cell injury and death. 26 In particular, PTH-mediated intracellular Ca 2ϩ accumulation, coupled to induction of excessive oxidative stress in cardiomyocytes and their mitochondria, has been linked to cell death and subsequent myocardial tissue repair.…”

“…Moreover, Ca 2ϩ overload has been related to the electric remodeling and arrhythmogenic potential characterizing cardiomyocytes in heart failure. 22 The complexity of PTH functions is further highlighted by data indicating the existence of a bidirectional link between PTH and the renin-angiotensin-aldosterone-system, which may be relevant for the regulation of calcium metabolism and in the pathogenesis of cardiovascular disease. 22,27 In particular, PTH can stimulate aldosterone secretion directly from the adrenals 27 and indirectly by modulating angiotensin II signaling.…”

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

“…This response is exacerbated in people with 25[OH]D deficiency [30,31]. The consequences of 25[OH]D deficiency [32] and elevated PTH levels [33][34][35][36] are calcium loading, with cardiomyocyte and skeletal muscle contractile dysfunction, cellular hypertrophy, oxidative stress, immune activation, endothelial dysfunction (including enhanced endothelin-1 release) [30,34,[37][38][39][40][41]. These influences are reflected clinically with an increased risk of hospitalisation [7,42], and worsening renal function [43], whilst vitamin D supplementation may be associated with a reduction of plasma renin and aldosterone levels [44,45].…”