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Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2003 Nov; Vol. 112 (9), pp. 1419-28. - Publication Year :
- 2003
-
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 renin-angiotensin 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.
- Subjects :
- Adaptation, Physiological
Animals
Arteries physiology
Blood Pressure
Body Weight
Cardiac Output
Collagen analysis
Elastin genetics
Elastin physiology
Heart Rate
Hypertension genetics
Mice
Mice, Inbred C57BL
Muscle, Smooth, Vascular physiology
Phenylephrine pharmacology
Proliferating Cell Nuclear Antigen analysis
Renin-Angiotensin System physiology
Elastin deficiency
Hypertension etiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 112
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 14597767
- Full Text :
- https://doi.org/10.1172/JCI19028