Efficacy of reversal of aortic calcification by chelating agents

Calcif Tissue Int. 2013 Nov;93(5):426-35. doi: 10.1007/s00223-013-9780-0.

Abstract

Elastin-specific medial vascular calcification, termed "Monckeberg's sclerosis," has been recognized as a major risk factor for various cardiovascular events. We hypothesize that chelating agents, such as disodium ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), and sodium thiosulfate (STS) might reverse elastin calcification by directly removing calcium from calcified tissues into soluble calcium complexes. We assessed the chelating ability of EDTA, DTPA, and STS on removal of calcium from hydroxyapatite (HA) powder, calcified porcine aortic elastin, and calcified human aorta in vitro. We show that both EDTA and DTPA could effectively remove calcium from HA and calcified tissues, while STS was not effective. The tissue architecture was not altered during chelation. In the animal model of aortic elastin-specific calcification, we further show that local periadventitial delivery of EDTA loaded in to poly(lactic-co-glycolic acid) nanoparticles regressed elastin-specific calcification in the aorta. Collectively, the data indicate that elastin-specific medial vascular calcification could be reversed by chelating agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Aortic Diseases / drug therapy*
  • Aortic Diseases / pathology
  • Calcium / metabolism
  • Chelating Agents / pharmacology
  • Chelating Agents / therapeutic use*
  • Drug Evaluation, Preclinical
  • Edetic Acid / pharmacology
  • Edetic Acid / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pentetic Acid / pharmacology
  • Pentetic Acid / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Swine
  • Treatment Outcome
  • Vascular Calcification / drug therapy*
  • Vascular Calcification / pathology

Substances

  • Chelating Agents
  • Pentetic Acid
  • Edetic Acid
  • Calcium