PEDF promotes the repair of bone marrow endothelial cell injury and accelerates hematopoietic reconstruction after bone marrow transplantation

SummaryHepatic venocclusive disease causes considerable morbidity and mortality following bone marrow transplantation. There are two hypotheses regarding the aetiology of this syndrome; firstly that changes in plasma coagulation factors and natural anticoagulants lead to a prothrombotic state and secondly that endothelial cell activation stimulates intravascular deposition of fibrin. We have investigated these mechanisms by measuring the changes in proteins C and S and factors VII and X in the post transplant period and by using the plasma concentration of factor Vila as an in vivo marker of potential endothelial cell tissue factor expression. Protein C fell in both allograft and autograft patients but more so in the allografts. Similar results were found for factors VII and X. These changes were predominantly due to hepatic dysfunction induced by the chemo-radiotherapy. Factor Vila levels were unchanged in both the allograft and autograft patients. We conclude that there is no convincing evidence for a procoagulant state following BMT as there are both anticoagulant and procoagulant changes. The absence of any changes in factor Vila levels suggests that tissue factor was not exposed to the general circulation following BMT but does not exclude focal expression at the sites of thrombosis.

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Mediators of Endothelial Cell Injury Following Total Body Irradiation in Bone Marrow Transplant Patients: The Role of Thromboxane and Leukotrienes

Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Radiation Injury ◽

10.1007/978-1-4615-3520-1_150 ◽

1993 ◽

pp. 775-777

Author(s):

R. A. Cahill ◽

Y. Zhao ◽

M. Foegh ◽

T. Spitzer

Keyword(s):

Bone Marrow ◽

Endothelial Cell ◽

Bone Marrow Transplant ◽

Total Body Irradiation ◽

Cell Injury ◽

Marrow Transplant ◽

Endothelial Cell Injury ◽

Transplant Patients ◽

Total Body

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Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Cancers ◽

10.3390/cancers12020424 ◽

2020 ◽

Vol 12 (2) ◽

pp. 424

Author(s):

Tomohiro Horio ◽

Eriko Morishita ◽

Shohei Mizuno ◽

Kaori Uchino ◽

Ichiro Hanamura ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

High Risk ◽

Heme Oxygenase ◽

Marrow Transplantation ◽

Cell Injury ◽

Disease Free Survival ◽

Heme Oxygenase 1 ◽

Intracellular Enzyme ◽

Promoter Gene

Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.

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