Objective: 

The metalloproteinase ADAMTS-7 was identified in genome-wide association studies to be associated with coronary artery disease (CAD). It is also involved in the pathogenesis of rheumatoid arthritis supposedly through degradation of cartilage oligomeric matrix protein (COMP). The pathogenetic mechanisms involving ADAMTS-7 in atherosclerosis are largely unknown. We examined whether the deletion of Adamts-7 modifies vascular remodelling after vessel injury in mice or affects blood lipid levels contributing to atherosclerosis.

Methods: 

To investigate the functional role of Adamts-7 in structural remodelling we generated Adamts-7 deficient mice by interrupting the gene between exon 4 and exon 5 with an internal ribosome entry site followed by the lacZ gene. Vascular remodelling was studied by ligation of the left common carotid artery. Ten days after ligation vessels were explanted, cryosectioned and morphometrically analyzed after hematoxylin eosin staining. In a subset of experiments, mice were fed a Western diet for 15 weeks and their weight and blood lipids assessed. Atherosclerotic lesions were quantified at the sinus aortae at the end of this period after Oil-Red-O staining.

Results: 

Adamts-7 deficient mice were viable and grew to normal size without obvious phenotype. Carotid ligation induced neointima formation occluding up to one third of the lumen in wt-mice. In contrast, neointima was almost absent in vessels of Adamts-7 deficient-mice. Thus, media area, neointima area and neointima-media-ratio were significantly smaller in the Adamts-7 deficient mice. Weight gain and blood lipid levels following the Western diet were similar in both genotypes. Lipid deposition at the sinus aortae was only sparse after this diet but not different between both genotypes.

Conclusion: 

Adamts-7 seems to be essential for the structural remodelling of arteries following vascular injury in mice. Since atherogenic metabolic parameters and lipid deposition were unaltered, we suggest that the association of ADAMTS-7 and CAD involves a remodelling mechanism in the vessel wall itself.