Therapeutic Applications of Calcium Metabolism Modulation in Heart Disease

Med Chem. 2016;12(2):177-83. doi: 10.2174/157340641202160209103313.

Abstract

Cardiovascular disease is the leading cause of death worldwide and there is extensive research on the pathophysiology of all its clinical entities. Despite the big array of possible therapeutic modalities for cardiovascular disease, there is still a big necessity to develop novel treatments that will augment our strategies for tackling the burden of cardiovascular disease and decrease morbidity and mortality. A major player in both the physiology and pathophysiology of the cardiovascular system is calcium. Extracellular calcium is required in order to initiate cardiac muscle contraction and promote the calcium-induced calcium release mechanism from the sarcoplasmic reticulum. A lot of molecules and structures that in a direct or indirect way interact with calcium are being studied and there is a constant flow of new information that is emerging. In this review we focus on some of these calcium metabolism modulators representatives such as SERCA2a, RyR2, S100A1, phosholamban and calcineurin. We emphasize on their mechanism of action, their role in cardiovascular disease and potential therapeutic implications. We also focus on the effect the bisphosphonates might have in regression of the calcium deposition in the human arteries as well as the usage of novel biomarkers such as mircoRNAs in calcium metabolism modulation in heart disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / metabolism
  • Calcineurin / metabolism
  • Calcium / metabolism*
  • Calcium-Binding Proteins / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Diphosphonates / pharmacology
  • Diphosphonates / therapeutic use
  • Heart Diseases / drug therapy*
  • Heart Diseases / metabolism
  • Heart Failure / drug therapy
  • Heart Failure / metabolism
  • Humans
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use
  • MicroRNAs / metabolism
  • Myocardial Ischemia / drug therapy
  • Myocardial Ischemia / metabolism
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • S100 Proteins / metabolism
  • SUMO-1 Protein / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Vitamin D / metabolism
  • Zoledronic Acid

Substances

  • Calcium-Binding Proteins
  • Diphosphonates
  • Imidazoles
  • MicroRNAs
  • Ryanodine Receptor Calcium Release Channel
  • S100 Proteins
  • S100A1 protein
  • SUMO-1 Protein
  • phospholamban
  • Vitamin D
  • Zoledronic Acid
  • Cyclic AMP-Dependent Protein Kinases
  • Calcineurin
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium