N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice

Chen, Junmei; Adili, Reheman; Gushiken, Francisca C.; Nolasco, Leticia; Fu, Xiaoyun; Moake, Joel L.; Ni, Heyu; López, José A.

doi:10.1172/jci41062

Cited by 207 publications

(200 citation statements)

References 42 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…As our platform matures, we anticipate that μVNs can be used to test drugs and drug-delivery strategies that target microvascular function (for example, angiogenesis (47) and hypertension) (48) or blood-endothelium interactions (for example, sickle cell disease (49) and thrombotic thrombocytopenic purpura) (50). Scaffolds with μVNs could also provide a starting point for the growth of vascularized tissues in vitro for applications in regenerative medicine (51).…”

Section: Discussionmentioning

confidence: 99%

In vitro microvessels for the study of angiogenesis and thrombosis

Zheng

Chen

Craven

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

785

842

View full text Add to dashboard Cite

Microvascular networks support metabolic activity and define microenvironmental conditions within tissues in health and pathology. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of complex vascular phenomena, including angiogenesis and thrombosis. We have engineered living microvascular networks in three-dimensional tissue scaffolds and demonstrated their biofunctionality in vitro. We describe the lithographic technique used to form endothelialized microfluidic vessels within a native collagen matrix; we characterize the morphology, mass transfer processes, and long-term stability of the endothelium; we elucidate the angiogenic activities of the endothelia and differential interactions with perivascular cells seeded in the collagen bulk; and we demonstrate the nonthrombotic nature of the vascular endothelium and its transition to a prothrombotic state during an inflammatory response. The success of these microvascular networks in recapitulating these phenomena points to the broad potential of this platform for the study of cardiovascular biology and pathophysiology.tissue engineering | regenerative medicine | microfluidics | cancer | blood T he microvasculature is an extensive organ that mediates the interaction between blood and tissues. It defines the biological and physical characteristics of the microenvironment within tissues and plays a role in the initiation and progression of many pathologies, including cancer (1) and cardiovascular diseases (2, 3). Conventional planar cultures fail to recreate the in vivo physiology of the microvasculature with respect to three-dimensional (3D) geometry (lumens and axial branching points), and interactions of endothelium with perivascular cells, extracellular tissue and blood flow (4). Studies of the microvasculature in vivo allow only limited control of physical, chemical, and biological parameters influencing the microvasculature and present challenges with respect to observation (5). In vitro cultures that produce tubular vessels within 3D matrices will aid in elucidation of the roles of the microvasculature in health and disease. Important progress has been made toward this goal: Biologically derived or synthetic materials have been used to generate macrovessel tubes (6) and endothelialized microtubes (7); cellular self-assembly has been used to generate random microvasculature (8); microfabrication has been used to define complex geometries in hydrogels at the micro-scale (9); and distributions of cells and biochemical factors within 3D scaffolds (10). Of particular note, the group of Tien has pioneered the use of collagen to template the growth of vascular endothelium (7, 11) and demonstrated appropriate permeability (7), response to cyclic AMP (12), and differential properties as a function of the luminal shear stress and composition of the medium (13). Nonetheless, prior methodologies have been unable to produce endothelialized networks that can undergo substantial remodeling via angiogenesis; elucidate the ...

show abstract

Section: Discussionmentioning

confidence: 99%

In vitro microvessels for the study of angiogenesis and thrombosis

Zheng

Chen

Craven

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

785

842

View full text Add to dashboard Cite

show abstract

“…In addition, administration of NAC to ADAMTS13-deficient mice reduces plasma vWF multimers and leads to rapid resolution of thrombi. 25 Recently, the use of NAC as adjunctive treatment in a patient with refractory TTP was apparently efficient. 26 However, some failures were also reported.…”

Section: Cyclophosphamidementioning

confidence: 99%

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

Coppo

Froissart

2015

Hematology

View full text Add to dashboard Cite

Daily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of 80%-85%. However, relapses occur in ϳ40% of patients and refractory disease with fatal outcomes still occurs. In this context, the introduction of rituximab has probably been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, or even as frontline therapy, with high response rates. In more severe patients, salvage strategies may include twice-daily TPE, pulses of cyclophosphamide, vincristine, as well as splenectomy in more desperate cases.In this life-threatening disease, relapse prevention represents a major goal. Persistent severe acquired ADAMTS13 deficiency in patients who are otherwise in remission is associated with a high risk of relapse and preemptive treatment with rituximab may be considered in this context.In the coming years, the TTP therapeutic landscape should be enriched by original strategies stemming from clinical experience and new agents that are currently being evaluated in large, ideally international, clinical trials. Promising agents under evaluation include N-acetylcysteine, bortezomib, recombinant ADAMTS13, and inhibitors of the glycoprotein-Ib/IX-von Willebrand factor axis. Learning Objectives• Patients with acquired TTP who experience a suboptimal response (refractoriness or disease exacerbation) with standard management need a more intensive treatment • Salvage therapies typically include rituximab, and in the more severe cases twice daily plasma exchange, boluses of cyclophosphamide, vincristine, and splenectomy • A persistent severe acquired ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses

show abstract

“…It replenishes hepatic glutathione depleted by drug conjugation [25]. Recently, clinical studies reported its potential antioxidant activity in protection against contrast induced nephropathy [26] and thrombosis [27]. Also, it has anti-inflammatory properties reported in several tissues like in cerebral and pulmonary inflammation [28,29].…”

Section: Introductionmentioning

confidence: 99%