ABSTRACT
The goal of this work was to determine a correlation between the VE-cadherin and circulating endothelial cells (CECs) blood levels at hemorrhagic fever with renal syndrome (HFRS) of different severity and research association between the VE-cadherin gene c. 1550T>C missense mutation and HRFS severity. Significant decreasing of the VE-cadherin and increasing of CECs blood levels in the course of the disease in all studied groups was established. Most prominent changes were found at severe type with complications. There was found a strong negative correlation between these two indexes. There was significant high frequency of homozygotic genotype *T/*T at severe type with complications. It was concluded that there was increased endothelium desquamation due to the VE-cadherin internalization at moderate and severe uncomplicated types of HFRS and as a result ofVE-cadherin gene c. 1550T>C missense mutation at severe type with complications.
Subject(s)
Antigens, CD , Cadherins , Endothelium, Vascular/pathology , Gene Frequency/genetics , Hemorrhagic Fever with Renal Syndrome , Adult , Antigens, CD/blood , Antigens, CD/genetics , Cadherins/blood , Cadherins/genetics , Endothelial Cells/cytology , Endothelial Cells/metabolism , Gene Expression , Genetic Association Studies , Genotype , Hemorrhagic Fever with Renal Syndrome/blood , Hemorrhagic Fever with Renal Syndrome/genetics , Hemorrhagic Fever with Renal Syndrome/pathology , Hemorrhagic Fever with Renal Syndrome/virology , Homozygote , Humans , Male , Middle Aged , Mutation, Missense , Puumala virus/genetics , Puumala virus/pathogenicityABSTRACT
The aim of study was to determine the probable sources of circulating endothelial cells (CECs) and establish the role of both VE-cadherin and vascular endothelial growth factor (VEGF) in molecular mechanism of endothelium desquamation using the hemorrhagic fever with renal syndrome as the model of endothelium injury. Autopsy pieces of kidney, liver, lung, brain, stomach and myocardium taken from 10 patients were studied histologically. Quantitative measurement of CECs was performed by the method developed by J. Hladovec (1978). Blood levels of VE-cadherin and VEGF were determined by ELISA method. Predominant sources CECs were found to be macro- and microvessels of kidney, liver, lung, brain, gastric mucous membrane, myocardium and, possibly - brain vessels. One of the molecular mechanism of endothelium desquamation is VEGF-stimulated internalization of VE-cadherin.
Subject(s)
Endothelial Cells/pathology , Endothelium, Vascular/pathology , Hemorrhagic Fever with Renal Syndrome/blood , Hemorrhagic Fever with Renal Syndrome/pathology , Adult , Cadherins/metabolism , Cell Count , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Enzyme-Linked Immunosorbent Assay , Hemorrhagic Fever with Renal Syndrome/metabolism , Humans , Vascular Endothelial Growth Factor A/metabolismABSTRACT
A reversible inhibitor of Na,K-ATPase (M(r) approximately 190 Da, Ki = 4 x 10(-7) M) has been isolated from rat brain tissue. The inhibitor has no structural analogs among currently known endogenous inhibitors of Na,K-ATPase.
