The Role of ADAMTS Proteoglycanases in Thoracic Aortic Disease

Abstract

Thoracic aortic aneurysm and dissection (TAAD) are complex disease states with high morbidity and mortality that pose significant challenges to early diagnosis. Patients with an aneurysm are asymptomatic and typically present to the emergency department only after the development of a dissection. The extracellular matrix (ECM) plays a crucial role in regulating the aortic structure and function. The histopathologic hallmark termed medial degeneration is characterised by smooth muscle cell (SMC) loss, the degradation of elastic and collagen fibres and proteoglycan (PG) accumulation. Covalently attached to the protein core of PGs are a number of glycosaminoglycan chains, negatively charged molecules that provide flexibility, compressibility, and viscoelasticity to the aorta. PG pooling in the media can produce discontinuities in the aortic wall leading to increased local stress. The accumulation of PGs is likely due to an imbalance between their synthesis by SMCs and decreased proteolysis by A Disintegrin-like and Metalloproteinase with Thrombospondin motifs (ADAMTS) proteoglycanases in the ECM. Mouse models of TAAD indicated that these proteases exert a crucial, albeit complex and not fully elucidated, role in this disease. This has led to a mounting interest in utilising ADAMTS proteoglycanases as biomarkers of TAAD. In this review, we discuss the role of ADAMTSs in thoracic aortic disease and their potential use in facilitating the clinical diagnosis of TAAD and disease progression.

Endogenous chondroitin extends the lifespan and healthspan in C. elegans

“…7 ). Given that ADAMTS proteases in mammals often degrade proteoglycans, it is plausible that the substrates of MIG-17 might include CPGs 26 .

Figure 7 Model for the CPG-mediated regulation of aging.

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Role of ADAM and ADAMTS proteases in pathological tissue remodeling

“…In another study, a decrease of ADAMTS5 was found in acute aortic dissection (AAD), which was associated with apoptosis of ASMCs. In vitro experiments showed that recombinant ADAMTS5 protected ASMCs from Ang II-induced cell apoptosis, while the underlying mechanism was unclear [ 37 , 38 ]. In diabetic cardiomyopathy, decreased myocardial apoptosis by conditional deletion of Adam17 ameliorates myocardial remodeling and dysfunction.…”