Plasma D-dimer concentration in patients with systemic sclerosis

Marie, I.; Borg, Jeanne‐Yvonne; Hellot, M.-F.; Lévesque, H.

doi:10.1111/j.1365-2133.2007.08313.x

Cited by 8 publications

(23 citation statements)

References 16 publications

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“…Additionally, plasmin is known to regulate vascular endothelial functions, and influence the progression of various cardiovascular diseases through fibrinolysis, the degradation of matrix proteins, and the activation of growth factors [ 20 ]. The levels of plasmin-α2AP and D-dimer are elevated in patients with SSc [ 21 , 22 ], and plasmin may also affect vascular dysfunction in SSc. α2AP may cause vascular disorder not only through inhibition of VEGF responses but also through plasmin inhibition.…”

Section: Discussionmentioning

confidence: 99%

α2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis: the roles of α2AP in vascular dysfunction in systemic sclerosis

et al. 2017

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BackgroundSystemic sclerosis (SSc) is a connective tissues disease of unknown origin characterized by vascular damage and extensive fibrosis. Recently, we demonstrated that α2-antiplasmin (α2AP) is associated with the development of fibrosis in SSc. We herein investigate the roles of α2AP in vascular dysfunction in SSc.MethodsVascular damage in mice was determined by the levels of blood vessels and blood flow. Vascular functions in vascular endothelial cells (ECs) were determined by the levels of tube formation, cell proliferation, and endothelial junction-associated protein (VE-cadherin and PECAM1) production.ResultsThe administration of α2AP induced vascular damage in mice. Conversely, the α2AP neutralization improved vascular damage in a bleomycin-induced mouse model of SSc. Additionally, we showed that the SSc fibroblast-conditioned media induced the reduction of tube formation, cell proliferation, and endothelial junction-associated protein production in ECs, and that α2AP neutralization improved them. We also examined the mechanisms underlying the effects of α2AP on vascular alteration in SSc and found that α2AP attenuated vascular endothelial growth factor-induced tube formation, cell proliferation, and endothelial junction-associated protein production through the adipose triglyceride lipase/tyrosine phosphatase SHP2 axis in ECs.ConclusionOur findings demonstrate that α2AP is associated with vascular alteration, and that the blocking of α2AP improves vascular dysfunction in SSc.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1227-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

α2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis: the roles of α2AP in vascular dysfunction in systemic sclerosis

et al. 2017

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“…Furthermore, integrin αIIb and glycoprotein Ibβ, receptors for von Willebrand factor expressing on platelets, are abnormally up-regulated in SSc [ 39 ]. Given that sensitive markers of fibrinolytic enhancement, such as plasma levels of D-dimer and plasmin-α2-plasmin inhibitor complex (PIC), are elevated in SSc patients [ 51 , 52 , 53 , 54 ], the altered balance of coagulation/fibrinolysis system appears to cause a variable degree of luminal thrombosis following vascular injury, contributing to impaired peripheral circulation, the induction of inflammation and the subsequent activation of vascular cells (endothelial cells and pericytes/vascular smooth muscle cells) and fibroblasts [ 55 , 56 , 57 ].…”

Section: The Common Ssc-specific Pathologic Cascade Across Multiplmentioning

confidence: 99%

The Pathogenesis of Systemic Sclerosis: An Understanding Based on a Common Pathologic Cascade across Multiple Organs and Additional Organ-Specific Pathologies

Asano

2020

JCM

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Systemic sclerosis (SSc) is a multisystem autoimmune and vascular disease resulting in fibrosis of various organs with unknown etiology. Accumulating evidence suggests that a common pathologic cascade across multiple organs and additional organ-specific pathologies underpin SSc development. The common pathologic cascade starts with vascular injury due to autoimmune attacks and unknown environmental factors. After that, dysregulated angiogenesis and defective vasculogenesis promote vascular structural abnormalities, such as capillary loss and arteriolar stenosis, while aberrantly activated endothelial cells facilitate the infiltration of circulating immune cells into perivascular areas of various organs. Arteriolar stenosis directly causes pulmonary arterial hypertension, scleroderma renal crisis and digital ulcers. Chronic inflammation persistently activates interstitial fibroblasts, leading to the irreversible fibrosis of multiple organs. The common pathologic cascade interacts with a variety of modifying factors in each organ, such as keratinocytes and adipocytes in the skin, esophageal stratified squamous epithelia and myenteric nerve system in gastrointestinal tract, vasospasm of arterioles in the heart and kidney, and microaspiration of gastric content in the lung. To better understand SSc pathogenesis and develop new disease-modifying therapies, it is quite important to understand the complex pathogenesis of SSc from the two distinct perspectives, namely the common pathologic cascade and additional organ-specific pathologies.

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“…It is reported that ECs synthesize tPA, uPA, uPAR, and PAI-1, and that fibrinolytic regulators play an important role in the maintenance of endothelial homeostasis [15,16,17,18,19,20]. The levels of plasmin-α2AP complex and D-dimer in plasma are elevated in SSc [21,22,23] and the expression of α2AP is elevated in fibrotic tissue of SSc model mice and dermal fibroblasts obtained from patients with SSc [24,25]. α2AP deficiency attenuates the development of fibrosis in SSc model mice [26,27] and uPAR deficiency promotes the development of fibrosis [28].…”

Section: Introductionmentioning

confidence: 99%

The Role of Fibrinolytic Regulators in Vascular Dysfunction of Systemic Sclerosis

Kanno

2019

IJMS

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Systemic sclerosis (SSc) is a connective tissue disease of autoimmune origin characterized by vascular dysfunction and extensive fibrosis of the skin and visceral organs. Vascular dysfunction is caused by endothelial cell (EC) apoptosis, defective angiogenesis, defective vasculogenesis, endothelial-to-mesenchymal transition (EndoMT), and coagulation abnormalities, and exacerbates the disease. Fibrinolytic regulators, such as plasminogen (Plg), plasmin, α2-antiplasmin (α2AP), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1), and angiostatin, are considered to play an important role in the maintenance of endothelial homeostasis, and are associated with the endothelial dysfunction of SSc. This review considers the roles of fibrinolytic factors in vascular dysfunction of SSc.

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Plasma D-dimer concentration in patients with systemic sclerosis

Cited by 8 publications

References 16 publications

α2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis: the roles of α2AP in vascular dysfunction in systemic sclerosis

α2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis: the roles of α2AP in vascular dysfunction in systemic sclerosis

The Pathogenesis of Systemic Sclerosis: An Understanding Based on a Common Pathologic Cascade across Multiple Organs and Additional Organ-Specific Pathologies

The Role of Fibrinolytic Regulators in Vascular Dysfunction of Systemic Sclerosis

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