Fig. 3.

Future directions for ADAMTSL proteins as potential genetic substrates, biomarkers, and therapeutic targets in cardiovascular disease. ADAMTSL2, ADAMTSL3 and ADAMTSL6 genetic variants have been identified in diseases of the heart and vasculature. Biallelic ADAMTSL2 variants cause the rare and deadly syndromes Geleophysic dysplasia and Al-Gazali dysplasia with several cardiac manifestations [10]. ADAMTSL3 is involved in rare chromosomal disorders with cardiovascular malformations [29, 45]. ADAMTSL6 heterozygous mutations give rise to aortic aneurysms [8]. ADAMTSLs have potential as circulatory biomarkers of cardiac fibrosis. ADAMTSL2 is a demonstrated biomarker of liver fibrosis [6] and predicts adverse events in heart failure [5], and ADAMTSL1 is independently associated with cardiac fibrosis in heart failure [4]. ADAMTSL proteins may be therapeutic targets to limit TGFβ activity in the heart and vasculature by overexpression or recombinant peptide delivery. Created with BioRender.com