Disruption of the elastin gene in adult Williams syndrome is accompanied by a paradoxical reduction in arterial stiffness.
Although the aetiology of Williams syndrome (WS) is related to elastin gene disruption, its pathogenesis remains unknown, particularly that of vascular lesions. The aim of the present study was to compare the elastic properties of three WS patients with age- and gender-matched normotensive and hypertensive controls. Common carotid arteries of WS patients had a higher distensibility, a thicker intima-media and a lower elastic modulus. Electron microscopy studies of one WS renal artery showed major abnormalities of the elastic fibres, which displayed a reticular structure and a thickening of the internal elastic lamina, whereas the ultrastructure of elastic fibres was normal in a control subadventitial muscular fibrodysplasia. In this WS arterial stenosis, we studied the expression patterns of several major smooth muscle (SM) phenotypic markers using immunofluorescence and used a normal renal artery as a control. In WS, SM-alpha-actin- and myosin-heavy-chain-positive cells contained low amounts of heavy caldesmon, and laminin-beta1 chain was expressed into the basement membranes, indicating a less differentiated phenotype. In conclusion, in WS patients, the carotid artery wall was abnormally distensible and thick, and major ultrastructural abnormalities of elastic fibres were observed in association with smooth muscle cell de-differentiation. These results indicate that the haplo-insufficiency of the elastin gene in WS patients leads to abnormal elastic fibre assembly within the media. Arterial wall hypertrophy found with a primary defect in elastin may represent a major factor responsible for increased distensibility. We suggest that, in WS, the increased proliferative response and the associated de-differentiation process represent two important mechanisms underlying the matrix accumulation and the development of arterial stenosis.
Lacolley
Patrick
P
INSERM EMI-U 0107, 15 rue de l'école de médecine, 75270 Paris cedex 06, France.
Boutouyrie
Pierre
P
Glukhova
Marina
M
Daniel Lamaziere
Jean-Marie
JM
Plouin
Pierre-François
PF
Bruneval
Patrick
P
Vuong
Phat
P
Corvol
Pierre
P
Laurent
Stéphane
S
D000328:Adult; D001794:Blood Pressure; D017536:Carotid Artery, Common / Q000503:physiopathology*; D002454:Cell Differentiation; D004547:Elastic Tissue / Q000648:ultrastructure; D004548:Elasticity; D004549:Elastin / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D012077:Renal Artery / Q000648:ultrastructure; D012078:Renal Artery Obstruction / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D018980:Williams Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
D004549:Elastin