ADAMTS Proteins and Vascular Remodeling in Aortic Aneurysms

Mougin, Zakaria; Herrero, Julia Huguet; Boileau, Cathérine; Goff, Carine Le

doi:10.3390/biom12010012

Cited by 8 publications

(7 citation statements)

References 89 publications

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“…Subcluster 3 (vascular smooth muscle, pericyte) expressed Acta2, Myh11, and Tagln, markers of smooth muscle, but also contained a subpopulation of cells expressing Sost and Cbr2 that are similar to heart vascular mural cells (Muhl et al, 2020), Rgs5 and Cspg4 that mark pericytes (Tsukui et al, 2020), and Thsd4 (encoding ADAMTSL6), an ECM protein associated with elastic tissues (Mougin et al, 2021). Subcluster 4 cells expressed lung stromal markers, Col8a1, Igf1, Meis2 , and Pcsk5 , identified in Tabula Muris, but also specifically expressed Grm7 and Thbs4 , not found in the lung in Tabula Muris (Tabula Muris et al, 2018), suggesting a potentially unique lung adventitial cell type.…”

Section: Resultsmentioning

confidence: 99%

Identification of a myofibroblast differentiation program during neonatal lung development

Yin,

Koenitzer,

Patra

et al. 2023

Preprint

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Alveologenesis is the final stage of lung development in which the internal surface area of the lung is increased to facilitate efficient gas exchange in the mature organism. The first phase of alveologenesis involves the formation of septal ridges (secondary septae) and the second phase involves thinning of the alveolar septa. Within secondary septa, mesenchymal cells include a transient population of alveolar myofibroblasts (MyoFB) and a stable but poorly described population of lipid rich cells that have been referred to as lipofibroblasts or matrix fibroblasts (MatFB). Using a uniqueFgf18CreERlineage trace mouse line, cell sorting, single cell RNA sequencing, and primary cell culture, we have identified multiple subtypes of mesenchymal cells in the neonatal lung, including an immature progenitor cell that gives rise to mature MyoFB. We also show that the endogenous and targeted ROSA26 locus serves as a sensitive reporter for MyoFB maturation. These studies identify a myofibroblast differentiation program that is distinct form other mesenchymal cells types and increases the known repertoire of mesenchymal cell types in the neonatal lung.Summary StatementDuring primary alveologenesis, alveolar myofibroblasts comprise a distinct proliferative mesenchymal lineage that matures and populates emerging secondary septa.

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Section: Resultsmentioning

confidence: 99%

Identification of a myofibroblast differentiation program during neonatal lung development

Yin,

Koenitzer,

Patra

et al. 2023

Preprint

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“…26,27 In addition, ECM remodeling can affect the expression of EC surface molecules, which can alter EC adhesion. 28,29 Understanding the dynamic changes of ECs and ECM remodeling in response to ischemic injury is important for the development of new therapeutic strategies for the treatment of heart diseases. 30,31 Here, we observed changes in critical proteins in ECs, leading to an increase in vasculature permeability in the subendocardial region of the ischemic myocardium.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Alteration of endothelial permeability ensures cardiomyocyte survival from ischemic insult in the subendocardium of the heart

Chu,

Song,

Xiao

et al. 2023

Exp Biol Med (Maywood)

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Previous studies have shown that cardiomyocytes in the subendocardial region of myocardium survive from ischemic insult. This study was undertaken to explore possible mechanisms for the survival of these cardiomyocytes, focusing on changes in endothelial cells (ECs) and blood supply. C57/B6 mice were subjected to permanent ligation of left anterior descending (LAD) coronary artery to induce myocardial ischemia (MI). The hearts were harvested at 1, 4, and 7 days post MI and examined for histological changes. It was found that the survival of cardiomyocytes was associated with a preservation of ECs in the subendocardial region, as revealed by EC-specific tdTomato expression transgenic mice ( Tie2tdTomato). However, the EC selective proteins, PECAM1 and VEGFR2, were significantly depressed in these ECs. Consequently, the ratio of PECAM1/tdTomato was significantly decreased, indicating a transformation from PECAM1+ ECs to PECAM1− ECs. Furthermore, EC junction protein, VE-cadherin, was not only depressed but also disassociated from PECAM1 in the same region. These changes led to an increase in EC permeability, as evidenced by increased blood infiltration in the subendocardial region. Thus, the increase in the permeability of ECs due to their transformation in the subendocardial region allows blood infiltration, creating a unique microenvironment and ensuring the survival of cardiomyocytes under ischemic conditions.

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“…Differences in the choice of the model (BAPN versus AngII, for example) and time points selected for the abrogation of Adamts function (embryonic or post-natal) make it even harder to assess their contribution to TAAD. The substrate repertoire of the ADAMTS proteases discussed in this review extends beyond PGs [7,73]. Additionally, it cannot be excluded that the ADAMTS proteoglycanases discussed in this review may exert functions that are independent of their proteolytic activity.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 97%

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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ADAMTS Proteins and Vascular Remodeling in Aortic Aneurysms

Cited by 8 publications

References 89 publications

Identification of a myofibroblast differentiation program during neonatal lung development

Identification of a myofibroblast differentiation program during neonatal lung development

Alteration of endothelial permeability ensures cardiomyocyte survival from ischemic insult in the subendocardium of the heart

The Role of ADAMTS Proteoglycanases in Thoracic Aortic Disease

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