Inter-α-trypsin inhibitor heavy chain 4 is a novel marker of acute ischemic stroke

Kashyap, Rajpal S.; Nayak, Amit R.; Deshpande, Poonam S.; Kabra, Dinesh; Purohit, Hemant J.; Taori, Girdhar M.; Daginawala, Hatim F.

doi:10.1016/j.cca.2009.01.009

Cited by 83 publications

(74 citation statements)

References 21 publications

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“…In our earlier studies, we have reported that the expression of ITIH4 downregulates in AIS patients, and further it is normalized only in those patients whose health improved and not in those who either expired or their health deteriorated. Therefore, it could be a novel marker for prognosis of AIS [12] . Thus, an increase in ITIH4 level in the follow-up serum sample of AIS patients suggests sustained anti-inflammatory activity [28] .…”

Section: Discussionmentioning

confidence: 99%

“…Some of them such as neuron-specific enolase (NSE), S100ββ protein, glial fibrillary acidic protein, myelin basic protein, creatine kinase isoenzyme BB, tau protein, matrix metalloproteinase-9 were found to be very promising in predicting outcomes in AIS patients [10,11] . In an earlier study, we reported that the serum level of Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) protein (120-kDa) could be a useful biomarker for prognosis of AIS patients [12,13] . Regardless of this, there are very limited studies for evaluating the impact of comorbidity risk factors of AIS on the diagnostic and prognostic potential of these biomarkers.…”

Section: Prediction Of Outcome In Diabeticmentioning

confidence: 99%

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Prediction of Outcome in Diabetic Acute Ischemic Stroke Patients: A Hospital-Based Pilot Study Report

Nayak

Badar²,

Lande

et al. 2016

Ann Neurosci

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Background: Demographic and clinical characteristics are known to influence the outcome in acute ischemic stroke (AIS) patients. Purpose: This study is aimed at evaluating short- and long-term outcomes in diabetic AIS patients. In addition, the study also evaluates the impact of diabetes on the performance of indigenously reported biomarker, inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and known biomarkers, neuron-specific enolase (NSE) and glial-derived S-100 beta beta protein (S-100ββ). Methods: This study was performed on 29 diabetes and 75 non-diabetes AIS patients. Outcome of AIS patients was analyzed by using modified Rankin scale at discharge, then at 12 and 18 months after discharge. Based on the obtained scores, patients were classified as improved group (scales 1-3) and dependent/expired group (scales 3-6). Blood samples were collected during admission and at discharge/expired time. Levels of NSE, S100ββ, and ITIH4 were analyzed in all samples. Results: On discharge, frequencies of dependent/expired outcome were 4/29 (14%) and 19/75 (17%) in diabetic and non-diabetic AIS patients. However, follow-up outcome at 12 and 18 months showed higher dependent/expired cases of 43 and 41% among diabetic AIS patients compared to 27 and 21% in non-diabetic patients. Multivariate analysis revealed that diabetes is an independent risk factor for dependent/expired outcome in AIS patients (OR 0.484 (at discharge); 1.307 (at 12 months) and 1.675 (at 18 months)). NSE, S100ββ, and ITIH4 showed a differential expression in both the outcome groups of AIS patients, irrespective of diabetes. Conclusion: Diabetes increases the risk of dependent/expired outcome in AIS patients. Also, serum NSE, S100ββ, and ITIH4 are independent biomarkers for prognosis of outcome in AIS patients, irrespective of diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Prediction Of Outcome In Diabeticmentioning

confidence: 99%

Prediction of Outcome in Diabetic Acute Ischemic Stroke Patients: A Hospital-Based Pilot Study Report

Nayak

Badar²,

Lande

et al. 2016

Ann Neurosci

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“…SMCs costimulated with agonistic anti-LTbR and TNF-α also upregulated multiple chemokines, such as Ccl2 and Ccl5, as well as vascular cell adhesion molecule-1 and intracellular adhesion molecule-1. 44 Although not addressed experimentally, the reduction of both local and circulating levels of Ccl5 may contribute to the observed phenotype in apoE 47 , an inhibitor of calcification, and genes involved in the finetuning of inflammatory responses, such as inter α trypsin inhibitor 48 and the lectins Lgals4 and Lgals6. 49 Taken together, these findings support the hypothesis that LTbR on monocytes stimulates monocyte recruitment into atherosclerotic lesions and also promotes plaque inflammation, in part, by activating the Ccl5/Ccr5 pathway, thereby contributing to atheroprogression.…”

Section: Grandoch Et Al Lymphotoxin β Receptor Promotes Atherosclerosmentioning

confidence: 99%

Deficiency in Lymphotoxin β Receptor Protects From Atherosclerosis in apoE-Deficient Mice

Grandoch

Feldmann

Göthert

et al. 2015

Circulation Research

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Rationale: Lymphotoxin β receptor (LTbR) regulates immune cell trafficking and communication in inflammatory diseases. However, the role of LTbR in atherosclerosis is still unclear. Objective: The aim of this study was to elucidate the role of LTbR in atherosclerosis. Methods and Results: After 15 weeks of feeding a Western-type diet, mice double-deficient in apolipoprotein E and LTbR (apoE −/− /LTbR −/− ) exhibited lower aortic plaque burden than did apoE −/− littermates. Macrophage content at the aortic root and in the aorta was reduced, as determined by immunohistochemistry and flow cytometry. In line with a decrease in plaque inflammation, chemokine (C–C motif) ligand 5 ( Ccl5 ) and other chemokines were transcriptionally downregulated in aortic tissue from apoE −/− /LTbR −/− mice. Moreover, bone marrow chimeras demonstrated that LTbR deficiency in hematopoietic cells mediated the atheroprotection. Furthermore, during atheroprogression, apoE −/− mice exhibited increased concentrations of cytokines, for example, Ccl5, whereas apoE −/− /LTbR −/− mice did not. Despite this decreased plaque macrophage content, flow cytometric analysis showed that the numbers of circulating lymphocyte antigen 6C (Ly6C) low monocytes were markedly elevated in apoE −/− /LTbR −/− mice. The influx of these cells into atherosclerotic lesions was significantly reduced, whereas apoptosis and macrophage proliferation in atherosclerotic lesions were unaffected. Gene array analysis pointed to chemokine (C–C motif) receptor 5 as the most regulated pathway in isolated CD115 + cells in apoE −/− /LTbR −/− mice. Furthermore, stimulating monocytes from apoE −/− mice with agonistic anti-LTbR antibody or the natural ligand lymphotoxin-α1β2, increased Ccl5 mRNA expression. Conclusions: These findings suggest that LTbR plays a role in macrophage-driven inflammation in atherosclerotic lesions, probably by augmenting the Ccl5-mediated recruitment of monocytes.

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“…Prior reports of ITIH4 in cattle were limited to isolation of the APP from the serum of heifers with experimentally induced summer mastitis (Pineiro et al, 2004). The association of ITIH4 with innate immunity has, however, been studied in models of acute inflammation in swine (Gonzalez-Ramon et al, 2000), and ITIH4 was recently reported to be a novel marker of acute ischemic stroke in humans (Kashyap et al, 2009). Previous research and similarity to a human homolog led to the classification of ITIH4 as a plasma kallikreinsensitive glycoprotein, but the exact role and function of ITIH4 in the bovine mammary gland during inflammation associated with coliform mastitis is not yet clear (Nishimura et al, 1995).…”

Section: Quantification Of Acute Phase Proteins In Bovine Milk Using mentioning

confidence: 99%

Veterinary Biomarker Discovery: Proteomic Analysis of Acute Phase Proteins

Boehmer¹,

Olumee-Shabon²

2011

Acute Phase Proteins as Early Non-Specific Biomarkers of Human and Veterinary Diseases

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Inter-α-trypsin inhibitor heavy chain 4 is a novel marker of acute ischemic stroke

Cited by 83 publications

References 21 publications

Prediction of Outcome in Diabetic Acute Ischemic Stroke Patients: A Hospital-Based Pilot Study Report

Prediction of Outcome in Diabetic Acute Ischemic Stroke Patients: A Hospital-Based Pilot Study Report

Deficiency in Lymphotoxin β Receptor Protects From Atherosclerosis in apoE-Deficient Mice

Veterinary Biomarker Discovery: Proteomic Analysis of Acute Phase Proteins

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