title: Elastin-insufficient mice show normal cardiovascular remodeling in 2K1C hypertension despite higher baseline pressure and unique cardiovascular architecture.
abstract: Mice heterozygous for the elastin gene (ELN(+/-)) show unique cardiovascular properties, including increased blood pressure and smaller, thinner arteries with an increased number of lamellar units. Some of these properties are also observed in humans with supravalvular aortic stenosis, a disease caused by functional heterozygosity of the elastin gene. The arterial geometry in ELN(+/-) mice is contrary to the increased thickness that would be expected in an animal demonstrating hypertensive remodeling. To determine whether this is due to a decreased capability for cardiovascular remodeling or to a novel adaptation of the ELN(+/-) cardiovascular system, we increased blood pressure in adult ELN(+/+) and ELN(+/-) mice using the two-kidney, one-clip Goldblatt model of hypertension. Successfully clipped mice have a systolic pressure increase of at least 15 mmHg over sham-operated animals. ELN(+/+) and ELN(+/-)-clipped mice show significant increases over sham-operated mice in cardiac weight, arterial thickness, and arterial cross-sectional area with no changes in lamellar number. There are no significant differences in most mechanical properties with clipping in either genotype. These results indicate that ELN(+/+) and ELN(+/-) hearts and arteries remodel similarly in response to adult induced hypertension. Therefore, the cardiovascular properties of ELN(+/-) mice are likely due to developmental remodeling in response to altered hemodynamics and reduced elastin levels.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Street, St. Louis, MO 63110, USA. jwagenseil@cellbiology.wustl.edu
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Wagenseil
authors.forename: Russell H
authors.initials: RH
authors.lastname: Knutsen
authors.forename: Dean Y
authors.initials: DY
authors.lastname: Li
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mecham
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure; D004549:Elastin / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020257:Ventricular Remodeling
chemical_list: D004549:Elastin