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.
Carta
Luca
L
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Wagenseil
Jessica E
JE
Knutsen
Russell H
RH
Mariko
Boubacar
B
Faury
Gilles
G
Davis
Elaine C
EC
Starcher
Barry
B
Mecham
Robert P
RP
Ramirez
Francesco
F
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