An update on vascular calcification and potential therapeutics

Mol Biol Rep. 2021 Jan;48(1):887-896. doi: 10.1007/s11033-020-06086-y. Epub 2021 Jan 4.

Abstract

Pathological calcification is a major cause of cardiovascular morbidities primarily in population with chronic kidney disease (CKD), end stage renal diseases (ERSD) and metabolic disorders. Investigators have accepted the fact that vascular calcification is not a passive process but a highly complex, cell mediated, active process in patients with cardiovascular disease (CVD) resulting from, metabolic insults of bone fragility, diabetes, hypertension, dyslipidemia and atherosclerosis. Over the years, studies have revealed various mechanisms of vascular calcification like induction of bone formation, apoptosis, alteration in Ca-P balance and loss of inhibition. Novel clinical studies targeting cellular mechanisms of calcification provide promising and potential avenues for drug development. The interventions include phosphate binders, sodium thiosulphate, vitamin K, calcimimetics, vitamin D, bisphosphonates, Myoinositol hexaphosphate (IP6), Denosumab and TNAP inhibitors. Concurrently investigators are also working towards reversing or curing pathological calcification. This review focuses on the relationship of vascular calcification to clinical diseases, regulators and factors causing calcification including genetics which have been identified. At present, there is lack of any significant preventive measures for calcifications and hence this review explores further possibilities for drug development and treatment modalities.

Keywords: Cardiovascular disease; Chronic kidney disease; Vascular calcification.

Publication types

  • Review

MeSH terms

  • Atherosclerosis / drug therapy*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Calcimimetic Agents / therapeutic use
  • Calcium / metabolism
  • Denosumab / therapeutic use
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Diphosphonates / therapeutic use
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / metabolism
  • Dyslipidemias / pathology
  • Enzyme Inhibitors / therapeutic use
  • Homeostasis / drug effects
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / pathology
  • Inositol Phosphates / therapeutic use
  • Phosphorus / metabolism
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / pathology
  • Thiosulfates / therapeutic use
  • Vascular Calcification / drug therapy*
  • Vascular Calcification / metabolism
  • Vascular Calcification / pathology
  • Vitamin D / therapeutic use
  • Vitamin K / therapeutic use

Substances

  • Calcimimetic Agents
  • Diphosphonates
  • Enzyme Inhibitors
  • Inositol Phosphates
  • Thiosulfates
  • Vitamin K
  • Vitamin D
  • Phosphorus
  • Denosumab
  • sodium thiosulfate
  • Calcium