Predictive value of serum transthyretin for outcome in acute ischemic stroke

Ambrosius, Wojciech; Michalak, Sławomir; Kaźmierski, Radosław; Andrzejewska, Natalia; Kozubski, Wojciech

doi:10.1371/journal.pone.0179806

Cited by 13 publications

(13 citation statements)

References 29 publications

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“…Reduced AFM and TTR, which we found in the cardioembolic vs. large-vessel stroke comparison and in the CBS deficiency (Table 3), were also observed in Han Chinese ischemic stroke patients [25]. Notably, reduced TTR is associated with poor prognosis in ischemic stroke patients [28].…”

Section: Discussionmentioning

confidence: 67%

Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes

Sikora

Kupc

et al. 2019

IJMS

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Ischemic stroke induces brain injury via thrombotic or embolic mechanisms involving large or small vessels. Cystathionine β-synthase deficiency (CBS), an inborn error of metabolism, is associated with vascular thromboembolism, the major cause of morbidity and mortality in affected patients. Because thromboembolism involves the brain vasculature in these patients, we hypothesize that CBS deficiency and ischemic stroke have similar molecular phenotypes. We used label-free mass spectrometry for quantification of changes in serum proteomes in CBS-deficient patients (n = 10) and gender/age-matched unaffected controls (n = 14), as well as in patients with cardioembolic (n = 17), large-vessel (n = 26), or lacunar (n = 25) ischemic stroke subtype. In CBS-deficient patients, 40 differentially expressed serum proteins were identified, of which 18 were associated with elevated homocysteine (Hcy) and 22 were Hcy-independent. We also identified Hcy-independent differentially expressed serum proteins in ischemic stroke patients, some of which were unique to a specific subtype: 10 of 32 for cardioembolic vs. large-vessel, six of 33 for cardioembolic vs. lacunar, and six of 23 for large-vessel vs. lacunar. There were significant overlaps between proteins affected by CBS deficiency and ischemic stroke, particularly the cardioembolic subtype, similar to protein overlaps between ischemic stroke subtypes. Top molecular pathways affected by CBS deficiency and ischemic stroke subtypes included acute phase response signaling and coagulation system. Similar molecular networks centering on NFκB were affected by CBS deficiency and stroke subtypes. These findings suggest common mechanisms involved in the pathologies of CBS deficiency and ischemic stroke subtypes.

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Section: Discussionmentioning

confidence: 67%

Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes

Sikora

Kupc

et al. 2019

IJMS

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“…Moreover, TTR stability and/or its levels are reduced in type 1 diabetes [ 23 , 41 ] and in Alzheimer’s Disease [ 42 , 43 , 44 ]. Further, low serum TTR levels were shown to be associated with an increased risk of mortality in patients with dialysis [ 45 ] and acute ischemic stroke [ 46 ]. On the other hand, TTR levels have been demonstrated to be increased in the mouse model of obesity [ 47 ], type 2 diabetes [ 22 , 33 ], and in pregnant women with gestational diabetes [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver

Alemi

Oliveira

Tavares

et al. 2021

IJMS

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Transthyretin (TTR), a 55 kDa evolutionarily conserved protein, presents altered levels in several conditions, including malnutrition, inflammation, diabetes, and Alzheimer’s Disease. It has been shown that TTR is involved in several functions, such as insulin release from pancreatic β-cells, recovery of blood glucose and glucagon levels of the islets of Langerhans, food intake, and body weight. Here, the role of TTR in hepatic glucose metabolism was explored by studying the levels of glucose in mice with different TTR genetic backgrounds, namely with two copies of the TTR gene, TTR+/+; with only one copy, TTR+/-; and without TTR, TTR-/-. Results showed that TTR haploinsufficiency (TTR+/-) leads to higher glucose in both plasma and in primary hepatocyte culture media and lower expression of the influx glucose transporters, GLUT1, GLUT3, and GLUT4. Further, we showed that TTR haploinsufficiency decreases pyruvate kinase M type (PKM) levels in mice livers, by qRT-PCR, but it does not affect the hepatic production of the studied metabolites, as determined by 1H NMR. Finally, we demonstrated that TTR increases mitochondrial density in HepG2 cells and that TTR insufficiency triggers a higher degree of oxidative phosphorylation in the liver. Altogether, these results indicate that TTR contributes to the homeostasis of glucose by regulating the levels of glucose transporters and PKM enzyme and by protecting against mitochondrial oxidative stress.

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“…On a cellular level, it is harmful to cell survival following an ischaemic insult to the brain [24]. Patients suffering from an ischaemic stroke with an unfavourable outcome were found to have significantly lower TTR serum levels on admission [25]. On the contrary, TTR levels appear to be a negative predictor of poor outcome at three months following SAH [26].…”

Section: Discussionmentioning

confidence: 99%

CSF proteomics of patients with hydrocephalus and subarachnoid haemorrhage

Sokół

Urbaniak

Zaremba

et al. 2019

Translational Neuroscience

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BackgroundThe pathophysiology of brain injury following aneurysmal subarachnoid haemorrhage (SAH) is associated with numerous mediators. The aim of the study is to analyse protein changes after SAH in cerebrospinal fluid (CSF) using mass spectrometry (MS).MethodsCSF samples were obtained from forty-four control subjects, seven good outcome and ten poor outcome SAH patients. CSF samples were collected at specific time intervals after SAH (days 1, 5 and 10). MALDI-TOF (Matrix Assisted Laser Desorption/Ionization Time-of-Flight) and ClinProTools software were utilised for MS, MS/MS (Mass Spectrometry) spectra collection and analysis. Selected masses were identified. The MALDI-TOF profiling experiments allowed for the targeted selection of potential markers in SAH. The study was performed in three steps by comparison of CSF samples: (1) from the control group and SAH patients (both good and poor outcome groups); (2) collected on days 1, 5 and 10 within the groups of poor SAH and good SAH patients, respectively; (3) from poor outcome SAH and good outcome patients at days 1, 5 and 10.Results15 new proteins whose CSF level is alternated by SAH presence, SAH treatment outcome and time passed since aneurysm rupture were identified.ConclusionsWe demonstrated new proteins which might play a role in different stages of subarachnoid haemorrhage and could be a new target for further investigation.

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Predictive value of serum transthyretin for outcome in acute ischemic stroke

Cited by 13 publications

References 29 publications

Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes

Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes

Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver

CSF proteomics of patients with hydrocephalus and subarachnoid haemorrhage

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