Discrete contributions of elastic fiber components to arterial development and mechanical compliance.
OBJECTIVE
Even though elastin and fibrillin-1 are the major structural components of elastic fibers, mutations in elastin and fibrillin-1 lead to narrowing of large arteries in supravalvular aortic stenosis and dilation of the ascending aorta in Marfan syndrome, respectively. A genetic approach was therefore used here to distinguish the differential contributions of elastin and fibrillin-1 to arterial development and compliance.


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.
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Luca
L
Carta
Jessica E
JE
Wagenseil
Russell H
RH
Knutsen
Boubacar
B
Mariko
Gilles
G
Faury
Elaine C
EC
Davis
Barry
B
Starcher
Robert P
RP
Mecham
Francesco
F
Ramirez
D000818:Animals; D021921:Aortic Stenosis, Supravalvular / Q000209:etiology / Q000503:physiopathology; D001158:Arteries / Q000254:growth & development* / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D001696:Biomechanical Phenomena / Q000502:physiology; D003187:Compliance / Q000502:physiology; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D004549:Elastin / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008382:Marfan Syndrome / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D054392:Adipokines
D004549:Elastin; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse