Venous Thromboembolism in Rheumatoid Arthritis: The Added Effect of Disease Activity to Traditional Risk Factors

Omair, Mohammed A.; Alkhelb, Sara A; Ezzat, Sadeen E; Boudal, Ayah M; Bedaiwi, Mohamed; Almaghlouth, Ibrahim

doi:10.2147/oarrr.s284757

Cited by 13 publications

(4 citation statements)

References 87 publications

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“…7B ). However, in the absence of successful containment, overproduction of blood vessels, persistent inflammation, and dysfunctional coagulation determines the progression and therapeutic outcomes in cancer ( 41 , 56 ), diabetic retinopathy ( 57 ), and rheumatoid arthritis ( 58 ). The complexity of vasoinhibin actions under disease is exemplified in murine antigen-induced arthritis, where vasoinhibin ameliorates pannus formation and growth via an antiangiogenic mechanism but promotes joint inflammation by stimulating the inflammatory response of synovial fibroblasts ( 37 , 59 ).…”

Section: Discussionmentioning

confidence: 99%

Vasoinhibin’s Apoptotic, Inflammatory, and Fibrinolytic Actions Are in a Motif Different From Its Antiangiogenic HGR Motif

Robles,

Zamora,

Garcia-Rodrigo

et al. 2023

Endocrinology

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Vasoinhibin, a proteolytic fragment of the hormone prolactin, inhibits blood vessel growth (angiogenesis) and permeability, stimulates the apoptosis and inflammation of endothelial cells, and promotes fibrinolysis. The antiangiogenic and antivasopermeability properties of vasoinhibin were recently traced to the HGR motif located in residues 46 to 48 (H46-G47-R48), allowing the development of potent, orally active, HGR-containing vasoinhibin analogues for therapeutic use against angiogenesis-dependent diseases. However, whether the HGR motif is also responsible for the apoptotic, inflammatory, and fibrinolytic properties of vasoinhibin has not been addressed. Here, we report that HGR-containing analogues are devoid of these properties. Instead, the incubation of human umbilical vein endothelial cells with oligopeptides containing the sequence HNLSSEM, corresponding to residues 30 to 36 of vasoinhibin, induced apoptosis, nuclear translocation of NF-κB, expression of genes encoding leukocyte adhesion molecules (VCAM1 and ICAM1) and proinflammatory cytokines (IL1B, IL6, and TNF), and adhesion of peripheral blood leukocytes. Also, intravenous or intra-articular injection of HNLSSEM-containing oligopeptides induced the expression of Vcam1, Icam1, Il1b, Il6, and Tnf in the lung, liver, kidney, eye, and joints of mice and, like vasoinhibin, these oligopeptides promoted the lysis of plasma fibrin clots by binding to plasminogen activator inhibitor-1 (PAI-1). Moreover, the inhibition of PAI-1, urokinase plasminogen activator receptor, or NF-κB prevented the apoptotic and inflammatory actions. In conclusion, the functional properties of vasoinhibin are segregated into 2 different structural determinants. Because apoptotic, inflammatory, and fibrinolytic actions may be undesirable for antiangiogenic therapy, HGR-containing vasoinhibin analogues stand as selective and safe agents for targeting pathological angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Vasoinhibin’s Apoptotic, Inflammatory, and Fibrinolytic Actions Are in a Motif Different From Its Antiangiogenic HGR Motif

Robles,

Zamora,

Garcia-Rodrigo

et al. 2023

Endocrinology

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show abstract

“…By inhibiting angiogenesis, vasoinhibin could help counteract the proangiogenic action of growth factors and cytokines, whereas by stimulating apoptosis, inflammation, and fibrinolysis, vasoinhibin could promote the pruning of blood vessels, protective inflammatory reactions, and clot dissolution needed for tissue remodeling. However, in the absence of successful containment, overproduction of blood vessels, persistent inflammation, and dysfunctional coagulation determines the progression and therapeutic outcomes in cancer (41,51), diabetic retinopathy (52), and rheumatoid arthritis (53).…”

Section: Discussionmentioning

confidence: 99%

The apoptotic, inflammatory, and fibrinolytic actions of vasoinhibin are in a motif different from its antiangiogenic HGR motif

Robles,

Zamora,

Garcia-Rodrigo

et al. 2023

Preprint

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Vasoinhibin is a proteolytic fragment of the hormone prolactin that inhibits blood vessel growth (angiogenesis) and permeability, stimulates the apoptosis and inflammation of endothelial cells and promotes fibrinolysis. The antiangiogenic and antivasopermeability properties of vasoinhibin were recently traced to the HGR motif located in residues 46 to 48, allowing the development of potent, orally active, HGR-containing vasoinhibin analogs for therapeutic use against angiogenesis-dependent diseases. However, whether the HGR motif is also responsible for the apoptotic, inflammatory, and fibrinolytic properties of vasoinhibin has not been addressed. Here, we report that HGR-containing analogs are devoid of these properties. Instead, the incubation of human umbilical vein endothelial cells with oligopeptides containing the sequence HNLSSEM, corresponding to residues 30 to 36 of vasoinhibin, induced apoptosis, the nuclear translocation of NF-κB, the expression of genes encoding leukocyte adhesion molecules (VCAM1 and ICAM1) and proinflammatory cytokines (IL1B, IL6, TNF), and the adhesion of peripheral blood leukocytes. Also, the intravenous or intra-articular injection of HNLSSEM-containing oligopeptides induced the expression of Vcam1, Icam1, Il1b, Il6, Tnf in the lung, liver, kidney, eye, and joints of mice and, like vasoinhibin, these oligopeptides promoted the lysis of plasma fibrin clots by binding to plasminogen activator inhibitor-1 (PAI-1). Moreover, the inhibition of PAI-1, urokinase plasminogen activator receptor, or NF-κB prevented the apoptotic and inflammatory actions. In conclusion, the functional properties of vasoinhibin are segregated into two different structural determinants. Because apoptotic, inflammatory, and fibrinolytic actions may be undesirable for antiangiogenic therapy, HGR-containing vasoinhibin analogs stand as selective and safe agents for targeting pathological angiogenesis.

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“…mit Januskinase-Inhibitoren (JAKi), können mit einem erhöhten VTE-Risiko verbunden sein. Bei Patienten mit hohem VTE-Risiko kann eine Thromboseprophylaxe durch eine mechanische oder medikamentöse Therapie (Heparin, Warfarin und DOAC) erwogen werden [114].…”

Section: Antikoagulation Bei Patienten Mit Autoimmunerkrankungenunclassified

Risiko venöser Thromboembolien bei Autoimmunerkrankungen: Eine umfassende Übersicht

Menichelli,

Cormaci,

Marucci

et al. 2024

Kompass Autoimmun

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Autoimmunerkrankungen haben spezifische pathophysiologische Mechanismen, die zu einem erhöhten Risiko für arterielle und venöse Thrombosen führen. Das Risiko einer venösen Thromboembolie (VTE) variiert je nach Art und Stadium der Erkrankung sowie der begleitenden Therapie. In dieser Übersichtsarbeit werden die häufigsten Autoimmunerkrankungen wie Anti-Phospholipid-Syndrom, entzündliche Myositis, Polymyositis und Dermatomyositis, rheumatoide Arthritis, Sarkoidose, Sjögren-Syndrom, autoimmunhämolytische Anämie, systemischer Lupus erythematodes, systemische Sklerose, Vaskulitis und chronisch-entzündliche Darmerkrankungen behandelt. Darüber hinaus geben wir einen Überblick über die Pathophysiologie, die für das VTE-Risiko bei jeder Autoimmunerkrankung verantwortlich ist, und berichten über die aktuellen Indikationen für eine gerinnungshemmende Therapie zur Primär- und Sekundärprävention von VTE.

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Venous Thromboembolism in Rheumatoid Arthritis: The Added Effect of Disease Activity to Traditional Risk Factors

Cited by 13 publications

References 87 publications

Vasoinhibin’s Apoptotic, Inflammatory, and Fibrinolytic Actions Are in a Motif Different From Its Antiangiogenic HGR Motif

Vasoinhibin’s Apoptotic, Inflammatory, and Fibrinolytic Actions Are in a Motif Different From Its Antiangiogenic HGR Motif

The apoptotic, inflammatory, and fibrinolytic actions of vasoinhibin are in a motif different from its antiangiogenic HGR motif

Risiko venöser Thromboembolien bei Autoimmunerkrankungen: Eine umfassende Übersicht

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