The effects of thrombomodulin and activated protein C on the pathogenesis of multiple sclerosis

Balkuv, Ece; Varoğlu, Asuman Orhan; Işık, Nihal; Isbilen, Banu; Duruyen, Saadettin; Başaran, Recep; Koçer, Abdülkadir

doi:10.1016/j.msard.2016.05.017

Cited by 6 publications

(10 citation statements)

References 15 publications

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“…The literature data on TM levels in MS are discordant . As previously reported, no differences in TM levels between MS and HI were found, and association between TM levels and more severe disability was not confirmed . Despite the greater sample size in our study, the association between glatiramer acetate and TM levels was not confirmed .…”

Section: Discussioncontrasting

confidence: 94%

“…In addition, no associations of clinical or MRI outcomes with TM were found, which has been suggested to confer protection from demyelination in a mouse model of MS [24]. The literature data on TM levels in MS are discordant [17][18][19]. As previously reported, no differences in TM levels between MS and HI were found, and association between TM levels and more severe disability was not confirmed [19].…”

Section: Discussionmentioning

confidence: 74%

“…Evidence for increased cerebrospinal fluid (CSF) TM synthesis in progressive MS (P-MS) patients has been detected [16]. However, several other studies of plasma or serum TM in MS patients have yielded discordant results [17][18][19]. TFPI also suppresses production of pro-inflammatory cytokines such as tumor necrosis factor a and interleukin-6 and increases production of the anti-inflammatory cytokine, interleukin-10 [20].…”

Section: Introductionmentioning

confidence: 99%

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Hemostasis biomarkers in multiple sclerosis

Ziliotto

Bernardi

Jakimovski

et al. 2018

Euro J of Neurology

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Section: Discussioncontrasting

confidence: 94%

Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

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Hemostasis biomarkers in multiple sclerosis

Ziliotto

Bernardi

Jakimovski

et al. 2018

Euro J of Neurology

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“…In addition to vWF release as consequence of endothelial damage, the shedding of membrane proteins could be promoted. In this context, soluble TM has been the most investigated protein in MS (135, 138, 142, 146, 147). Studies on larger cohorts of MS patients concluded that TM concentration levels do not differ in plasma or in serum (138, 147).…”

Section: Coagulation and Hemostasis Findings In Multiple Sclerosis Pamentioning

confidence: 99%

Coagulation Pathways in Neurological Diseases: Multiple Sclerosis

et al. 2019

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Significant progress has been made in understanding the complex interactions between the coagulation system and inflammation and autoimmunity. Increased blood-brain-barrier (BBB) permeability, a key event in the pathophysiology of multiple sclerosis (MS), leads to the irruption into the central nervous system of blood components that include virtually all coagulation/hemostasis factors. Besides their cytotoxic deposition and role as a possible trigger of the coagulation cascade, hemostasis components cause inflammatory response and immune activation, sustaining neurodegenerative events in MS. Early studies showing the contribution of altered hemostasis in the complex pathophysiology of MS have been strengthened by recent studies using methodologies that permitted deeper investigation. Fibrin(ogen), an abundant protein in plasma, has been identified as a key contributor to neuroinflammation. Perturbed fibrinolysis was found to be a hallmark of progressive MS with abundant cortical fibrin(ogen) deposition. The immune-modulatory function of the intrinsic coagulation pathway still remains to be elucidated in MS. New molecular details in key hemostasis components participating in MS pathophysiology, and particularly involved in inflammatory and immune responses, could favor the development of novel therapeutic targets to ameliorate the evolution of MS. This review article introduces essential information on coagulation factors, inhibitors, and the fibrinolytic pathway, and highlights key aspects of their involvement in the immune system and inflammatory response. It discusses how hemostasis components are (dys)regulated in MS, and summarizes histopathological post-mortem human brain evidence, as well as cerebrospinal fluid, plasma, and serum studies of hemostasis and fibrinolytic pathways in MS. Studies of disease-modifying treatments as potential modifiers of coagulation factor levels, and case reports of autoimmunity affecting hemostasis in MS are also discussed.

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“…The genetic polymorphisms of PAI-1 are linked to lower PAI-1 plasma levels and are associated with increased risk of developing MS syndrome [125,126]. Furthermore, there is a statistically positive correlation between expanded disability status scale (EDSS) scores and TM levels in MS patients [127]. Studies conducted on 138 MS patients (85 RRMS and 53 P-MS) have demonstrated higher PAI-1 and TFPI levels in MS patients compared to healthy individuals [128].…”

Section: The Effect Of Metformin On Haemostasis and The Functioning Omentioning

confidence: 99%

Metformin as a Potential Agent in the Treatment of Multiple Sclerosis

Dziedzic

Saluk‐Bijak

Miller

et al. 2020

IJMS

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Metformin, a synthetic derivative of guanidine, is commonly used as an oral antidiabetic agent and is considered a multi-vector application agent in the treatment of other inflammatory diseases. Recent studies have confirmed the beneficial effect of metformin on immune cells, with special emphasis on immunological mechanisms. Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by various clinical courses. Although the pathophysiology of MS remains unknown, it is most likely a combination of disturbances of the immune system and biochemical pathways with a disruption of blood–brain barrier (BBB), and it is strictly related to injury of intracerebral blood vessels. Metformin has properties which are greatly desirable for MS therapy, including antioxidant, anti-inflammatory or antiplatelet functions. The latest reports relating to the cardiovascular disease confirm an increased risk of ischemic events in MS patients, which are directly associated with a coagulation cascade and an elevated pro-thrombotic platelet function. Hence, this review examines the potential favourable effects of metformin in the course of MS, its role in preventing inflammation and endothelial dysfunction, as well as its potential antiplatelet role.

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The effects of thrombomodulin and activated protein C on the pathogenesis of multiple sclerosis

Cited by 6 publications

References 15 publications

Hemostasis biomarkers in multiple sclerosis

Hemostasis biomarkers in multiple sclerosis

Coagulation Pathways in Neurological Diseases: Multiple Sclerosis

Metformin as a Potential Agent in the Treatment of Multiple Sclerosis

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