Nitric oxide degradation of heparin and heparan sulphate

Rolando E. Vilar, Dineshchandra Ghael, Min Li, Devan D. Bhagat, Lisa M. Arrigo, Mary Cowman, Harry S. Dweck, Louis Rosenfeld

Research output: Contribution to journalArticle

Abstract

NO is a bioactive free radical produced by NO synthase in various tissues including vascular endothelium. One of the degradation products of NO is HNO2, an agent known to degrade heparin and heparan sulphate. This report documents degradation of heparin by cultured endothelial-cell-derived as well as exogenous NO. An exogenous narrow molecular-mass preparation of heparin was recovered from the medium of cultured endothelial cells using strong-anion exchange. In addition, another narrow molecular-mass preparation of heparin was gassed with exogenous NO under argon. Degradation was evaluated by gel-filtration chromatography. Since HNO2 degrades heparin under acidic conditions, the reaction with NO gas was studied under various pH conditions. The results show that the degradation of exogenous heparin by endothelial cells is inhibited by NO synthase inhibitors. Exogenous NO gas at concentrations as low as 400 p.p.m. degrades heparin and heparan sulphate. Exogenous NO degrades heparin at neutral as well as acidic pH. Endothelial-cell-derived NO, as well as exogenous NO gas, did not degrade hyaluronan, an unrelated glycosaminoglycan that resists HNO2 degradation. Peroxynitrite, a metabolic product of the reaction of NO with superoxide, is an agent that degrades hyaluronan; however, peroxynitrite did not degrade heparin. Thus endothelial-cell-derived NO is capable of degrading heparin and heparan sulphate via HNO2 rather than peroxynitrite. These observations may be relevant to various pathophysiological processes in which extracellular matrix is degraded, such as bone development, apoptosis, tissue damage from inflammatory responses and possible release of growth factors and cytokines.

Original languageEnglish (US)
Pages (from-to)473-479
Number of pages7
JournalBiochemical Journal
Volume324
Issue number2
StatePublished - Jun 1 1997

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Heparitin Sulfate
Heparin
Nitric Oxide
Degradation
Endothelial cells
Endothelial Cells
Peroxynitrous Acid
Gases
Molecular mass
Hyaluronic Acid
Nitric Oxide Synthase
Cultured Cells
Tissue
Argon
Bone Development
Vascular Endothelium
Chromatography
Glycosaminoglycans
Superoxides
Free Radicals

ASJC Scopus subject areas

  • Biochemistry

Cite this

Vilar, R. E., Ghael, D., Li, M., Bhagat, D. D., Arrigo, L. M., Cowman, M., ... Rosenfeld, L. (1997). Nitric oxide degradation of heparin and heparan sulphate. Biochemical Journal, 324(2), 473-479.

Nitric oxide degradation of heparin and heparan sulphate. / Vilar, Rolando E.; Ghael, Dineshchandra; Li, Min; Bhagat, Devan D.; Arrigo, Lisa M.; Cowman, Mary; Dweck, Harry S.; Rosenfeld, Louis.

In: Biochemical Journal, Vol. 324, No. 2, 01.06.1997, p. 473-479.

Research output: Contribution to journalArticle

Vilar, RE, Ghael, D, Li, M, Bhagat, DD, Arrigo, LM, Cowman, M, Dweck, HS & Rosenfeld, L 1997, 'Nitric oxide degradation of heparin and heparan sulphate', Biochemical Journal, vol. 324, no. 2, pp. 473-479.
Vilar RE, Ghael D, Li M, Bhagat DD, Arrigo LM, Cowman M et al. Nitric oxide degradation of heparin and heparan sulphate. Biochemical Journal. 1997 Jun 1;324(2):473-479.
Vilar, Rolando E. ; Ghael, Dineshchandra ; Li, Min ; Bhagat, Devan D. ; Arrigo, Lisa M. ; Cowman, Mary ; Dweck, Harry S. ; Rosenfeld, Louis. / Nitric oxide degradation of heparin and heparan sulphate. In: Biochemical Journal. 1997 ; Vol. 324, No. 2. pp. 473-479.
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