1. Dysfunction of endothelial and smooth muscle cells in small arteries of a mouse model of Marfan syndrome.
- Author
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Syyong, HT, Chung, AWY, Yang, HHC, van Breemen, C, Syyong, H T, Chung, A W Y, and Yang, H H C
- Subjects
MARFAN syndrome ,SMOOTH muscle ,ENDOTHELIUM ,GENETIC mutation ,CONNECTIVE tissue diseases ,FIBRILLIN ,PHENYLEPHRINE ,LABORATORY mice ,ACETYLCHOLINE ,AGE distribution ,ALLELES ,ANIMAL experimentation ,BIOLOGICAL models ,VASODILATION ,CELLS ,COMPARATIVE studies ,ELASTICITY ,RESEARCH methodology ,MEDICAL cooperation ,MESENTERIC artery ,MICE ,MICROFILAMENT proteins ,RESEARCH ,RESEARCH funding ,SODIUM nitroferricyanide ,VASOCONSTRICTORS ,VASODILATORS ,EVALUATION research ,VASOCONSTRICTION ,PHARMACODYNAMICS - Abstract
Background and Purpose: 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.Experimental Approach: Second-order mesenteric arteries from mice at 3, 6 and 10 months of age (n= 30) heterozygous for the Fbn1 allele encoding a cysteine substitution (Fbn1(C1039G/+)) were compared with those from age-matched control littermates.Key Results: 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 potassium (60 mM)-induced membrane depolarization was decreased by at least 28% in Marfan vessels at all ages, while phenylephrine (3 microM)-induced contraction was reduced by at least 40% from 6 months. Acetylcholine-induced relaxation in Marfan vessels was reduced to 70% and 45% of control values, respectively, at 6 and 10 months. Sensitivity to sodium nitroprusside was reduced at 6 months (pEC(50)= 5.64 +/- 0.11, control pEC(50)= 7.34 +/- 0.04) and 10 months (pEC(50)= 5.99 +/- 0.07, control pEC(50)= 6.99 +/- 0.14). Pretreatment with N(omega)-Nitro-L-arginine methyl ester (200 microM) had no effect on acetylcholine-induced relaxation in Marfan vessels, but reduced vasorelaxation in control vessels to 57% of control values. Addition of indomethacin (10 microM) and catalase (1000 U.mL(-1)) further inhibited vasorelaxation in Marfan vessels to a greater degree compared with control vessels.Conclusions and Implications: Pathogenesis of Marfan syndrome in resistance-sized arteries increases stiffness and impairs vasomotor function. [ABSTRACT FROM AUTHOR]- Published
- 2009
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