Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency

Gilles Faury, Mylène Pezet, Russell H. Knutsen, Walter A. Boyle, Scott P. Heximer, Sean E. McLean, Robert K. Minkes, Kendall J. Blumer, Attila Kovacs, Daniel P. Kelly, Dean Y. Li, Barry Starcher, Robert P. Mecham

Research output: Contribution to journalArticle

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Abstract

Supravalvular aortic stenosis is an autosomal-dominant disease of elastin (Eln) insufficiency caused by loss-of-function mutations or gene deletion. Recently, we have modeled this disease in mice (Eln+/-) and found that Eln haploinsufficiency results in unexpected changes in cardiovascular hemodynamics and arterial wall structure. Eln+/- animals were found to be stably hypertensive from birth, with a mean arterial pressure 25-30 mmHg higher than their wild-type counterparts. The animals have only moderate cardiac hypertrophy and live a normal life span with no overt signs of degenerative vascular disease. Examination of arterial mechanical properties showed that the inner diameters of Eln+/- arteries were generally smaller than wild-type arteries at any given intravascular pressure. Because the Eln+/- mouse is hypertensive, however, the effective arterial working diameter is comparable to that of the normotensive wild-type animal. Physiological studies indicate a role for the reninangiotensin system in maintaining the hypertensive state. The association of hypertension with elastin haploinsufficiency in humans and mice strongly suggests that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension.

Original languageEnglish (US)
Pages (from-to)1419-1428
Number of pages10
JournalJournal of Clinical Investigation
Volume112
Issue number9
DOIs
StatePublished - Nov 2003

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Haploinsufficiency
Elastin
Cardiovascular System
Arteries
Supravalvular Aortic Stenosis
Wild Animals
Elastic Tissue
Gene Deletion
Cardiomegaly
Vascular Diseases
Arterial Pressure
Hemodynamics
Parturition
Hypertension
Pressure
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Faury, G., Pezet, M., Knutsen, R. H., Boyle, W. A., Heximer, S. P., McLean, S. E., ... Mecham, R. P. (2003). Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency. Journal of Clinical Investigation, 112(9), 1419-1428. https://doi.org/10.1172/JCI200319028

Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency. / Faury, Gilles; Pezet, Mylène; Knutsen, Russell H.; Boyle, Walter A.; Heximer, Scott P.; McLean, Sean E.; Minkes, Robert K.; Blumer, Kendall J.; Kovacs, Attila; Kelly, Daniel P.; Li, Dean Y.; Starcher, Barry; Mecham, Robert P.

In: Journal of Clinical Investigation, Vol. 112, No. 9, 11.2003, p. 1419-1428.

Research output: Contribution to journalArticle

Faury, G, Pezet, M, Knutsen, RH, Boyle, WA, Heximer, SP, McLean, SE, Minkes, RK, Blumer, KJ, Kovacs, A, Kelly, DP, Li, DY, Starcher, B & Mecham, RP 2003, 'Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency', Journal of Clinical Investigation, vol. 112, no. 9, pp. 1419-1428. https://doi.org/10.1172/JCI200319028
Faury, Gilles ; Pezet, Mylène ; Knutsen, Russell H. ; Boyle, Walter A. ; Heximer, Scott P. ; McLean, Sean E. ; Minkes, Robert K. ; Blumer, Kendall J. ; Kovacs, Attila ; Kelly, Daniel P. ; Li, Dean Y. ; Starcher, Barry ; Mecham, Robert P. / Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency. In: Journal of Clinical Investigation. 2003 ; Vol. 112, No. 9. pp. 1419-1428.
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