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Disturbed LDL and scavenger receptor functions in monocytes from chronic haemodialysed patients
Insights
Patients on chronic hemodialysis (HD) show impaired low-density lipoprotein (LDL) uptake and increased scavenger receptor activity, contributing to cardiovascular disease. Scavenger receptor dysfunction appears central to these complications in renal failure patients.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Lipid Metabolism
Background:
- Atherosclerosis is a common complication in patients with end-stage renal failure undergoing chronic hemodialysis (HD).
- While lipid and lipoprotein disorders are known, the expression and function of low-density lipoprotein (LDL) and scavenger receptors in HD patients are poorly understood.
Purpose of the Study:
- To investigate the expression and function of LDL and scavenger receptors in monocytes of chronic HD patients.
- To elucidate the role of these receptors in the pathogenesis of cardiovascular complications in HD patients.
Main Methods:
- Monocytes were isolated from 11 male chronic HD patients and 15 healthy male controls.
- (125)I-labelled LDL and acetylated LDL (acLDL) were used to study LDL and scavenger receptor binding and function.
Main Results:
- LDL binding to monocytes was reduced in HD patients compared to controls, diminishing LDL-induced inhibition of cholesterol synthesis.
- acLDL binding was significantly increased in HD patients, but triggered low apoE synthesis, leading to increased cholesterol inclusions in monocytes.
Conclusions:
- Disturbed LDL and scavenger receptor expression and function likely contribute to cardiovascular complications in chronic HD patients.
- Scavenger receptor dysfunction may be a key factor in the cardiovascular complications observed in HD patients with renal failure.
Background:
The most frequent complication in patients with end-stage renal failure on chronic haemodialysis (HD) treatment is atherosclerosis, i.e. the different forms of heart and vascular diseases. The complete disorder of serum lipid and lipoprotein patterns is well demonstrated, whereas our knowledge about the low-density lipoprotein (LDL) and scavenger receptor expression and function are poorly understood.
Methods:
In our current work, LDL and scavenger receptor expression and functions were simultaneously studied in monocytes obtained from 15 healthy male control subjects and from 11 chronic HD male patients applied with (125)I-labelled LDL, isolated from healthy volunteers. To study the scavenger LDL receptors, labelled acetylated LDL (acLDL) was used.
Results:
LDL binding to the monocytes of the HD-group was found to be decreased in comparison to that of the controls. As a result, the 50 microg LDL protein-induced inhibition of endogenous cholesterol synthesis was also diminished. In contrast, acLDL binding was greatly increased, though it could trigger only a low apoE synthesis. Consequently the number of cholesterol inclusions in monocytes was increased.
Conclusions:
The disturbed expression and function of LDL and scavenger receptors both may play significant roles in pathogenesis of cardiovascular complications in chronic HD patients. Based on our present results, it can be assumed that dysfunction of scavenger receptors is at the centre of cardiovascular complications of HD patients with renal failure.