Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome
Barbara R. Pober, Mark Johnson, Zsolt Urban
Barbara R. Pober, Mark Johnson, Zsolt Urban
View: Text | PDF
Science in Medicine

Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome

Abstract

Williams-Beuren syndrome (WBS) is a microdeletion disorder caused by heterozygous loss of approximately 1.5-Mb pairs of DNA from chromosome 7. Patients with WBS have a characteristic constellation of medical and cognitive findings, with a hallmark feature of generalized arteriopathy presenting as stenoses of elastic arteries and hypertension. Human and mouse studies establish that defects in the elastin gene, leading to elastin haploinsufficiency, underlie the arteriopathy. In this review we describe potential links between elastin expression and arteriopathy, possible explanations for disease variability, and current treatment options and their limitations, and we propose several new directions for the development of nonsurgical preventative therapies based on insights from elastin biology.

Authors

Barbara R. Pober, Mark Johnson, Zsolt Urban

×

Figure 5

Proposed mechanisms of elastin signaling.

Options: View larger image (or click on image) Download as PowerPoint
Proposed mechanisms of elastin signaling. (A) A 67-kDa EBP is thought to...
(A) A 67-kDa EBP is thought to form a receptor complex with protective protein/cathepsin A (PP) and transmembrane sialidase/neuraminidase (Sase). Elastin peptide binding to the receptor activates the L-type Ca2+ channel and G-proteins (Gα, β, γ) to activate the MAPK pathway (92). (B) A different pathway postulates a GPCR for tropoelastin. GPCR-elastin binding depresses cAMP levels by inhibiting adenylate cyclase (AC) and leads to increased actin polymerization through the Rho kinase pathway (87). (C) Cells can also sense the elastin content indirectly by binding to elastic fiber components such as fibrillins and fibulin-5 via integrins.