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Dysfunction of endothelial and smooth muscle cells in small arteries of a mouse model of Marfan syndrome
Author(s) -
Syyong Harley,
Chung Ada WY,
Yang Clarice HH,
Breemen Cornelis
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.575.1
Subject(s) - marfan syndrome , medicine , arterial stiffness , contraction (grammar) , phenylephrine , mesenteric arteries , endocrinology , aorta , cardiology , elastin , anatomy , pathology , artery , blood pressure
Marfan syndrome, a connective tissue disorder caused by mutations in FBN1 encoding fibrillin‐1, results in life‐threatening complications in the aorta, but little is known about its effects in resistance vasculature. Second‐order mesenteric arteries from mice at 3, 6, and 10 months of age heterozygous for the Fbn1 allele encoding a cysteine substitution ( Fbn1 C1039G/+ ) were compared with those from age‐matched control littermates. Stress‐strain curves indicated that arterial stiffness was increased at 6 and 10 months of age in Marfan vessels. Isometric force measurement revealed that contraction in response to high potassium‐induced membrane depolarization was significantly decreased in Marfan vessels at all ages, while both phenylephrine‐induced contraction and frequency of Ca 2+ oscillations was reduced by at least 40% from 6 months onward. In addition, both endothelium‐dependent and endothelium‐independent relaxation to acetylcholine and sodium nitroprusside, respectively, was also reduced starting at 6 months of age. We conclude that pathogenesis of Marfan syndrome in resistance‐sized arteries increases stiffness and impairs vasomotor function. This work was funded by CIHR of Canada.