Vascular Ehlers–Danlos Syndrome: A Good Experimental Model Is Needed for Development of Treatment Strategies

Abstract

The vascular form of the Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder. Patients have a reduced life span (under 50) due to spontaneous and often fatal rupture of blood vessels and hollow organs. Until very recently no evidence-based treatment had been available. VEDS results from mutations in the COL3A1 gene that encodes the chains of collagen type III and alters the sequence in the triple-helical domain. A mouse model of vEDS created by inactivation of the Col3a1 gene has been of limited use as only 5% of homozygous animals survived to adulthood. The haploinsufficiency for one COL3A1 allele is one of the genotypes resulting in vEDS. In this review we provide evidence that haploinsufficiency for Col3a1 in mice recapitulates features of vEDS in humans and might be used as an experimental model. There was a reduced level of aortic collagen and correspondingly reduced aortic wall strength. A spectrum of lesions was detected in the aorta similar to those observed in human patients. Lesions increased in number and age and were more common in male than in female mice. Furthermore, potential treatment strategies are discussed including the already tested beta-adrenergic receptor (AR)-blocker therapy, the inhibition of extracellular matrix degrading enzymes, and the only causative approach of selective silencing of the mutant form of COL3A1 by allele-specific RNA interference.