Versican V1 Proteolysis in Human Aorta in Vivo Occurs at the Glu 441-Ala442 Bond, a Site That Is Cleaved by Recombinant ADAMTS-1 and ADAMTS-4

Abstract

Mature human aorta contains a 70-kDa versican fragment, which reacts with a neoepitope antiserum to the C-terminal peptide sequence DPEAAE. This protein therefore appears to represent the G1 domain of versican VI (G1-DPEAAE 441), which has been generated in vivo by proteolytic cleavage at the Glu441-Ala442 bond, within the sequence DPEAAE 441-A442RRGQ. Because the equivalent aggrecan product (G1-NITEGE341) and brevican product (G1-EAVESE395) are generated by ADAMTS-mediated cleavage of the respective proteoglycans, we tested the capacity of recombinant ADAMTS-1 and ADAMTS-4 to cleave versican at Glu441-Ala442. Both enzymes cleaved a recombinant versican substrate and native human versican at the Glu441-Ala 442 bond and the mature form of ADAMTS-4 was detected by Western analysis of extracts of aortic intima. We conclude that versican VI proteolysis in vivo can be catalyzed by one or more members of the ADAMTS family of metalloproteinases.