Is There Enough Evidence to Support the Role of Glycosaminoglycans and Proteoglycans in Thoracic Aortic Aneurysm and Dissection?—A Systematic Review

Rai, Pratik; Robinson, Lucy; Davies, Hannah A.; Akhtar, Riaz; Field, Mark; Madine, Jillian

doi:10.3390/ijms23169200

Cited by 7 publications

(4 citation statements)

References 85 publications

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“…Plasma levels of aggrecan (ACAN), a multimodular proteoglycan (PG) protein, were significantly enhanced in plasma samples of ATAAD patients compared to samples from healthy patients [ 104 ]. Also, increased levels of PG) and glycosaminoglycan (GAG) were detected in the serum of ATAAD patients (Table 3 ) [ 170 ].…”

Section: Sporadic and Genetic Biomarkers In Ataa(d)mentioning

confidence: 99%

Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections

Ganizada,

Veltrop,

Akbulut

et al. 2024

Basic Res Cardiol

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Ascending thoracic aortic aneurysm (ATAA) remains a significant medical concern, with its asymptomatic nature posing diagnostic and monitoring challenges, thereby increasing the risk of aortic wall dissection and rupture. Current management of aortic repair relies on an aortic diameter threshold. However, this approach underestimates the complexity of aortic wall disease due to important knowledge gaps in understanding its underlying pathologic mechanisms.Since traditional risk factors cannot explain the initiation and progression of ATAA leading to dissection, local vascular factors such as extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) might harbor targets for early diagnosis and intervention. Derived from diverse embryonic lineages, VSMCs exhibit varied responses to genetic abnormalities that regulate their contractility. The transition of VSMCs into different phenotypes is an adaptive response to stress stimuli such as hemodynamic changes resulting from cardiovascular disease, aging, lifestyle, and genetic predisposition. Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA.This review aims to illuminate the current understanding of cellular and molecular characteristics associated with ATAA and dissection, emphasizing the need for a more nuanced comprehension of the impaired ECM–VSMC network.

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Section: Sporadic and Genetic Biomarkers In Ataa(d)mentioning

confidence: 99%

Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections

Ganizada,

Veltrop,

Akbulut

et al. 2024

Basic Res Cardiol

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“…They comprise a protein core and covalently bound glycosaminoglycan chains (GAGs) composed of negatively charged disaccharide units [28]. The most abundant GAG subtypes in aortic PGs include chondroitin sulphate (CS) (40-62.5%), followed by heparan sulphate (18-30.5%) [36]. GAGs attract cations like Na+ from the interstitial fluid to maintain electroneutrality, hence their ability to exert a Donnan osmotic pressure on the tissue [28].…”

Section: Proteoglycans and Biomechanical Properties Of The Aortamentioning

confidence: 99%

“…In a normal thoracic aorta, the overall PG content increases with age up until 30-40 years, beyond which it exhibits a gradual decline concomitant with an alteration in the GAGs subtypes [36]. An acute dissection is found to occur between 62.3-85.3 years of age [5], excluding CTD patients who have an earlier onset, which may suggest that in TAAD, there is no decrease in the overall PG levels after a certain age but, instead, an ongoing accumulation.…”

Section: Proteoglycans In Aortic Diseasementioning

confidence: 99%

The Role of ADAMTS Proteoglycanases in Thoracic Aortic Disease

Kemberi,

Salmasi,

Santamaria

2023

IJMS

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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.

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“…They used thermal-induced percolation to great effect, increasing the conductivity of the fibers as well as Young’s modulus, which may be of relevance, e.g., in cardiac tissue engineering. In a review by Rai et al [ 6 ], the involvement of glycosaminoglycans (GAGs) and proteoglycans (PGs) in thoracic aortic aneurysms and dissection was discussed systematically. While there is substantial evidence for GAG and PG involvement in pathological processes, clear cause-and-effect relationships still have to be established.…”

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confidence: 99%