Abstract | OBJECTIVE: METHODS AND RESULTS: Key parameters of cardiovascular function were compared among adult mice haploinsufficient for elastin (Eln(+/-)), fibrillin-1 (Fbn1(+/-)), or both proteins (dHet). Physiological and morphological comparisons correlate elastin haploinsufficiency with increased blood pressure and vessel length and tortuosity in dHet mice, and fibrillin-1 haploinsufficiency with increased aortic diameter in the same mutant animals. Mechanical tests confirm that elastin and fibrillin-1 impart elastic recoil and tensile strength to the aortic wall, respectively. Additional ex vivo analyses demonstrate additive and overlapping contributions of elastin and fibrillin-1 to the material properties of vascular tissues. Lastly, light and electron microscopy evidence implicates fibrillin-1 in the hypertension-promoted remodeling of the elastin-deficient aorta. CONCLUSIONS: These results demonstrate that elastin and fibrillin-1 have both differential and complementary roles in arterial wall formation and function, and advance our knowledge of the structural determinants of vascular physiology and disease.
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Authors | Luca Carta, Jessica E Wagenseil, Russell H Knutsen, Boubacar Mariko, Gilles Faury, Elaine C Davis, Barry Starcher, Robert P Mecham, Francesco Ramirez |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 29
Issue 12
Pg. 2083-9
(Dec 2009)
ISSN: 1524-4636 [Electronic] United States |
PMID | 19850904
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- FBN1 protein, human
- Fbn1 protein, mouse
- Fibrillin-1
- Fibrillins
- Microfilament Proteins
- Elastin
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Topics |
- Animals
- Aortic Stenosis, Supravalvular
(etiology, physiopathology)
- Arteries
(growth & development, pathology, physiology, physiopathology)
- Biomechanical Phenomena
(physiology)
- Compliance
(physiology)
- Disease Models, Animal
- Elastic Tissue
(pathology, physiology, physiopathology)
- Elastin
(deficiency, genetics, physiology)
- Extracellular Matrix
(metabolism)
- Fibrillin-1
- Fibrillins
- Humans
- Marfan Syndrome
(etiology, physiopathology)
- Mice
- Mice, Inbred C57BL
- Mice, Mutant Strains
- Microfilament Proteins
(deficiency, genetics, physiology)
- Phenotype
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