HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Novel arterial pathology in mice and humans hemizygous for elastin.

Abstract
Obstructive vascular disease is an important health problem in the industrialized world. Through a series of molecular genetic studies, we demonstrated that loss-of-function mutations in one elastin allele cause an inherited obstructive arterial disease, supravalvular aortic stenosis (SVAS). To define the mechanism of elastin's effect, we generated mice hemizygous for the elastin gene (ELN +/-). Although ELN mRNA and protein were reduced by 50% in ELN +/- mice, arterial compliance at physiologic pressures was nearly normal. This discrepancy was explained by a paradoxical increase of 35% in the number of elastic lamellae and smooth muscle in ELN +/- arteries. Examination of humans with ELN hemizygosity revealed a 2. 5-fold increase in elastic lamellae and smooth muscle. Thus, ELN hemizygosity in mice and humans induces a compensatory increase in the number of rings of elastic lamellae and smooth muscle during arterial development. Humans are exquisitely sensitive to reduced ELN expression, developing profound arterial thickening and markedly increased risk of obstructive vascular disease.
AuthorsD Y Li, G Faury, D G Taylor, E C Davis, W A Boyle, R P Mecham, P Stenzel, B Boak, M T Keating
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 102 Issue 10 Pg. 1783-7 (Nov 15 1998) ISSN: 0021-9738 [Print] United States
PMID9819363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Elastin
Topics
  • Animals
  • Aorta (pathology, physiology)
  • Arterial Occlusive Diseases (genetics, pathology, physiopathology)
  • Blotting, Northern
  • Compliance
  • Elastin (genetics)
  • Humans
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Tunica Media (pathology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: