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Efficacy of Reversal of Aortic Calcification by Chelating Agents

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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.

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Abbreviations

EDTA:

Disodium ethylene diamine tetraacetic acid

DTPA:

Diethylene triamine pentaacetic acid

STS:

Sodium thiosulfate

Ca:

Calcium

P:

Phosphorus

HA:

Hydroxyapatite

PLGA:

Poly(lactic-co-glycolic acid)

CaCl2 :

Calcium chloride

CAC:

Coronary artery calcification

MAC:

Medial arterial calcification

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Acknowledgement

The authors thank Dr. Michael E. Ward at Greenville Hospital System for providing samples of calcified human aorta and Dr. Tim Cooper at Ortec (Piedmont, SC) for gifting the PLGA polymer. This work was partially supported by the National Institutes of Health (P20GM103444, R01HL061652) and the Hunter Endowment at Clemson University.

Conflict of interest

The authors have stated that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Bioengineering, Clemson University, 501 Rhodes Engineering Research Center, Clemson, SC, 29634, USA

    Yang Lei, Arjun Grover, Aditi Sinha & Naren Vyavahare

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  1. Yang Lei
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  2. Arjun Grover
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  3. Aditi Sinha
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  4. Naren Vyavahare
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Correspondence to Naren Vyavahare.

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Lei, Y., Grover, A., Sinha, A. et al. Efficacy of Reversal of Aortic Calcification by Chelating Agents. Calcif Tissue Int 93, 426–435 (2013). https://doi.org/10.1007/s00223-013-9780-0

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  • DOI: https://doi.org/10.1007/s00223-013-9780-0

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