Chemical-induced, nonlethal, developmental model of dissecting aortic aneurysm

Bin Gong, Margaret B. Trent, Deepak Srivastava, Paul J. Boor

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

BACKGROUND: A chemical-induced, nonlethal, dissecting aortic aneurysm (DAA) is described following in utero exposure to semicarbazide, an inhibitor of the vascular enzyme semicarbazide sensitive amine oxidase (SSAO). METHODS: Sprague-Dawley rat dams were given semicarbazide (0.096-49.000 mg/kg/day) by IP injection on gestation days (GDs) 14-20, a period of rapid aortic development. Newborn rats (day 1) were killed and their thoracic organs were removed en bloc for near-serial cross sections and routine histopathology, Movat stain for elastin, and immunohistochemistry to differentiate cells involved in the evolution of the DAA. In subsequent experiments, pups from treated dams (0.096-6.125 mg/kg/day) were allowed to survive for 7 or 28 days. RESULTS: DAA occurred in nearly 100% of the rats at all doses except the lowest tested (1.530, 0.096 mg/kg/day). Dissections frequently extended to the carotids and, less frequently, to the abdominal aorta. Remodeling of vascular lesions proceeded by organization of collections of blood in vascular media (the "false lumen"), proliferation of vascular smooth muscle cells, fibrosis, and formation of irregular frayed elastic lamellae in healed vascular media. Biochemical quantitation and Western blot analysis of main extracellular matrix proteins on GD 20 showed no overt difference in expression of collagen type I, fibrillin-1, or elastin. CONCLUSION: This developmental model provides investigators an opportunity to explore the pathologic mechanisms of DAA and to examine the potential long-term effects of vascular remodeling of DAA.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume76
Issue number1
DOIs
StatePublished - Jan 2006

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Dissecting Aneurysm
Aortic Aneurysm
Tunica Media
Elastin
Amine Oxidase (Copper-Containing)
Pregnancy
Extracellular Matrix Proteins
Abdominal Aorta
Enzyme Inhibitors
Collagen Type I
Vascular Smooth Muscle
Smooth Muscle Myocytes
Blood Vessels
Sprague Dawley Rats
Dissection
Fibrosis
Coloring Agents
Thorax
Western Blotting
Immunohistochemistry

ASJC Scopus subject areas

  • Developmental Biology

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Chemical-induced, nonlethal, developmental model of dissecting aortic aneurysm. / Gong, Bin; Trent, Margaret B.; Srivastava, Deepak; Boor, Paul J.

In: Birth Defects Research Part A - Clinical and Molecular Teratology, Vol. 76, No. 1, 01.2006, p. 29-38.

Research output: Contribution to journalArticle

Gong, Bin ; Trent, Margaret B. ; Srivastava, Deepak ; Boor, Paul J. / Chemical-induced, nonlethal, developmental model of dissecting aortic aneurysm. In: Birth Defects Research Part A - Clinical and Molecular Teratology. 2006 ; Vol. 76, No. 1. pp. 29-38.
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