Serine proteases of the complement lectin pathway and their genetic variations in ischaemic stroke

Tsakanova, Gohar; Stepanyan, Ani; Nahapetyan, Karen; Sim, Robert B.; Arakelyan, Arsen; Boyajyan, Anna

doi:10.1136/jclinpath-2017-204403

Cited by 15 publications

(12 citation statements)

References 48 publications

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“…We did not find differences between IS patients and controls, but ICH patients had significantly lower PLG protein amounts. MASP1 concentration was increased in myocardial infarction, however, in IS was reported to be either increased or decreased, whereas in ICH and SAH, lower levels were found (56)(57)(58). In our study, we detected higher MASP1 protein amount in IS than in healthy controls as well as in ICH.…”

Section: Review Of the Literature And Integrative Evaluationcontrasting

confidence: 40%

Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

et al. 2021

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Background: A reliable distinction between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is required for diagnosis-specific treatment and effective secondary prevention in patients with stroke. However, in resource-limited settings brain imaging, which is the current diagnostic gold standard for this purpose, is not always available in time. Hence, an easily accessible and broadly applicable blood biomarker-based diagnostic test differing stroke subtypes would be desirable. Using an explorative proteomics approach, this pilot study aimed to identify novel blood biomarker candidates for distinguishing IS from ICH.Material and Methods: Plasma samples from patients with IS and ICH were drawn during hospitalization and were analyzed by using liquid chromatography/mass spectrometry. Proteins were identified using the human reference proteome database UniProtKB, and label-free quantification (LFQ) data were further analyzed using bioinformatic tools.Results: Plasma specimens of three patients with IS and four patients with ICH with a median National Institute of Health Stroke Scale (NIHSS) of 12 [interquartile range (IQR) 10.5–18.5] as well as serum samples from two healthy volunteers were analyzed. Among 495 identified protein groups, a total of 368 protein groups exhibited enough data points to be entered into quantitative analysis. Of the remaining 22 top-listed proteins, a significant difference between IS and ICH was found for Carboxypeptidase N subunit 2 (CPN2), Coagulation factor XII (FXII), Plasminogen, Mannan-binding lectin serine protease 1, Serum amyloid P-component, Paraoxonase 1, Carbonic anhydrase 1, Fibulin-1, and Granulins.Discussion: In this exploratory proteomics-based pilot study, nine candidate biomarkers for differentiation of IS and ICH were identified. The proteins belong to the immune system, the coagulation cascade, and the apoptosis system, respectively. Further investigations in larger cohorts of patients with stroke using additional biochemical analysis methods, such as ELISA or Western Blotting are now necessary to validate these markers, and to characterize diagnostic accuracy with regard to the development of a point-of-care-system for use in resource-limited areas.

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Section: Review Of the Literature And Integrative Evaluationcontrasting

confidence: 40%

Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

et al. 2021

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“…Double Masp1/Masp2 knock-out ischemic mice were also not protected (Orsini et al, 2016). In a study carried out in the Armenian population, it was found that patients with ischemic stroke had higher proteolytic activity of MASP-1 and MASP-2, than controls (5.8 and 3.7 times more, respectively) (Tsakanova et al, 2018). Taken together, the evidence warrants further investigation with MASP levels and polymorphisms (Tables 1 and 2) in the susceptibility to cerebral vascular ischemia, especially within the context of COVID-19 disease.…”

Section: Cerebrovascular Diseasesmentioning

confidence: 96%

MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19

et al. 2021

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Components of the complement system and atypical parameters of coagulation were reported in COVID-19 patients, as well as the exacerbation of the inflammation and coagulation activity. Mannose binding lectin (MBL)-associated serine proteases (MASPs) play an important role in viral recognition and subsequent activation of the lectin pathway of the complement system and blood coagulation, connecting both processes. Genetic variants of MASP1 and MASP2 genes are further associated with different levels and functional efficiency of their encoded proteins, modulating susceptibility and severity to diseases. Our review highlights the possible role of MASPs in SARS-COV-2 binding and activation of the lectin pathway and blood coagulation cascades, as well as their associations with comorbidities of COVID-19. MASP-1 and/or MASP-2 present an increased expression in patients with COVID-19 risk factors: diabetes, arterial hypertension and cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and cerebrovascular disease. Based also on the positive results of COVID-19 patients with anti-MASP-2 antibody, we propose the use of MASPs as a possible biomarker of the progression of COVID-19 and the investigation of new treatment strategies taking into consideration the dual role of MASPs, including MASP inhibitors as promising therapeutic targets against COVID-19.

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“…Particularly, the results indicated that the activities of MASP-1 and MASP-2 are elevated in the blood of ischemic stroke patients compared with control subjects. 11 , 14 Moreover, we found that the rs3203210 and rs28945073 single nucleotide polymorphisms (SNPs) in the MASP1 gene and the rs147270785 SNP in MASP2 are strongly associated with ischemic stroke. 14 …”

Section: Introductionmentioning

confidence: 98%

“…11 , 14 Moreover, we found that the rs3203210 and rs28945073 single nucleotide polymorphisms (SNPs) in the MASP1 gene and the rs147270785 SNP in MASP2 are strongly associated with ischemic stroke. 14 …”

Section: Introductionmentioning

confidence: 98%

Pattern Recognition Molecules of Lectin Complement Pathway in Ischemic Stroke

Tsakanova¹,

Stepanyan²,

Steffensen³

et al. 2021

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Serine proteases of the complement lectin pathway and their genetic variations in ischaemic stroke

Cited by 15 publications

References 48 publications

Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19

Pattern Recognition Molecules of Lectin Complement Pathway in Ischemic Stroke

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