Developmental vasculotoxicity associated with inhibition of semicarbazide-sensitive amine oxidase

S. D. Langford, M. B. Trent, A. Balakumaran, P. J. Boor

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The endogenous substrate(s) and physiological function(s) of semicarbazide-sensitive amine oxidase (SSAO), a group of enzymes exhibiting highest activity in vascular smooth muscle cells of the mammalian aortic wall, remain undetermined. This study examines the pathophysiological effects in the thoracic aortic wall resulting from specific in vivo SSAO inhibition. Weanling Sprague-Dawley rats were treated acutely or chronically with either semicarbazide hydrochloride or the allylamine derivatives MDL-72274 or MDL- 72145 (Marion Merrell Dow Research Institute, Cincinnati, OH). Treatment with these compounds produced acute (6 and 24 h) and chronic (21 day) lowering of SSAO activity in aorta and lung with little effect on the activity of the vital matrix-forming enzyme, lysyl oxidase, in aortas of chronically treated animals. Chronic SSAO inhibition produced lesions consisting of striking disorganization of elastin architecture within the aortic media accompanied by degenerative medial changes and metaplastic changes in vascular smooth muscle cells. No significant difference in the total weight of dry, lipid- extracted aortic elastin and collagen components were observed between chronically SSAO inhibited and control animals. However, the amount of mature elastin was lowered and mature collagen was raised in the aortas of animals treated chronically with semicarbazide. Descending thoracic aortic rings isolated from chronically SSAO-inhibited animals had larger cross-sectional diameters (i.e., exhibited dilation) when compared to corresponding rings from control animals. This study demonstrates that developmental toxicity, characterized by striking vascular lesions and dilated thoracic aortas, can result from specific in vivo SSAO inhibition, suggesting a role for SSAO in connective tissue matrix development and maintenance, and specifically in the development of normal elastin.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalToxicology and Applied Pharmacology
Volume155
Issue number3
DOIs
StatePublished - Mar 15 1999

Fingerprint

Amine Oxidase (Copper-Containing)
Elastin
Animals
Aorta
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Collagen
Allylamine
Cells
Protein-Lysine 6-Oxidase
Thoracic Wall
Enzymes
Thoracic Aorta
Connective Tissue
Blood Vessels
Sprague Dawley Rats
Toxicity
Rats
Dilatation

Keywords

  • Aorta
  • Collagen
  • Developmental toxicity
  • Elastin
  • Lysyl oxidase
  • Semicarbazide-sensitive amine oxidase

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Developmental vasculotoxicity associated with inhibition of semicarbazide-sensitive amine oxidase. / Langford, S. D.; Trent, M. B.; Balakumaran, A.; Boor, P. J.

In: Toxicology and Applied Pharmacology, Vol. 155, No. 3, 15.03.1999, p. 237-244.

Research output: Contribution to journalArticle

Langford, S. D. ; Trent, M. B. ; Balakumaran, A. ; Boor, P. J. / Developmental vasculotoxicity associated with inhibition of semicarbazide-sensitive amine oxidase. In: Toxicology and Applied Pharmacology. 1999 ; Vol. 155, No. 3. pp. 237-244.
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