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(Circulation. 1999;99:909-915.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

Endothelial Function in Marfan Syndrome

Selective Impairment of Flow-Mediated Vasodilation

Dirk G. Wilson, MB, MRCP (UK); Michael F. Bellamy, MB, MRCP (UK); Mark W. Ramsey, BM, MRCP (UK); Jonathan Goodfellow, MB, MRCP (UK); Moira Brownlee, RGN; Sally Davies, MA, MRCP (UK); John F. Wilson, BSc, PhD; Malcolm J. Lewis, MB, DSc; A. Graham Stuart, MB, MRCP (UK)

From the Congenital Heart Disease Center (D.G.W., A.G.S.) and Institute of Medical Genetics (S.D.), University Hospital of Wales Healthcare NHS Trust, and the Cardiovascular Sciences Research Group (M.F.B., M.W.R., J.G., M.B., J.F.W., M.J.L.), University of Wales College of Medicine, Cardiff, Wales, UK.

Correspondence to Dr Dirk G. Wilson, Congenital Heart Disease Center, University Hospital of Wales Healthcare NHS Trust, Heath Park, Cardiff, Wales, UK CF4 4XW.

Background—The cardiovascular complications of Marfan syndrome arise due to alterations in the structural and functional properties of fibrillin, a constituent of vascular connective tissues. Fibrillin-containing microfibrils are closely associated with arterial endothelial cells, indicating a possible functional role for fibrillin in the endothelium. Plasma concentrations of endothelial cell products are elevated in Marfan subjects, which indirectly indicates endothelial dysfunction. This study directly assessed flow- and agonist-mediated endothelium-dependent brachial artery reactivity in Marfan subjects.

Methods and Results—In 20 Marfan and 20 control subjects, brachial artery diameter, blood flow, and blood pressure were measured by ultrasonic wall tracking, Doppler ultrasound, and photoplethysmography, respectively. Measurements were taken during hand hyperemia (a stimulus for endothelium-derived nitric oxide [NO] release in the upstream brachial artery) and after sublingual administration of the endothelium-independent vasodilator nitroglycerin. In 9 Marfan and 6 control subjects, the above parameters were also assessed during intra-arterial infusions of acetylcholine and bradykinin (agonists that stimulate NO production) and N^G-monomethyl-L-arginine (L-NMMA, an inhibitor of NO production). Flow-mediated responses differed markedly between Marfan and control subjects (-1.6±3.5% versus 6.50±4.1%, respectively; P<0.0001), whereas nitroglycerin produced similar vasodilation (14.2±5.7% versus 15.2±7.8%; P=NS). Agonist-induced vasodilation to incremental intra-arterial infusions of acetylcholine and bradykinin were not significantly different between Marfan and control subjects, and intra-arterial L-NMMA produced similar reductions in brachial artery diameter in both groups.

Conclusions—These data demonstrate impaired flow-mediated but preserved agonist-mediated endothelium-dependent vasodilation in Marfan subjects and suggest preservation of basal NO release. Selective loss of flow-mediated dilation suggests a role for fibrillin in endothelial cell mechanotransduction.

Key Words: Marfan syndrome • endothelium • arteries • endothelium-derived factors

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