Related Experiment Videos
High-density lipoproteins inhibit fibrinogen binding on adenosine diphosphate-activated monocytes
Insights
High-density lipoprotein (HDL) inhibits fibrinogen binding on monocytes, a key step in atherosclerosis development. This finding reveals a novel mechanism for how HDL may prevent arteriosclerosis by reducing monocyte recruitment and foam cell formation.
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Lipoprotein Metabolism
Background:
- Elevated fibrinogen and low high-density lipoprotein (HDL) cholesterol are risk factors for coronary heart disease.
- Monocytes, expressing the fibrinogen-binding protein CD11b/CD18, are crucial in atherosclerotic lesion formation.
Purpose of the Study:
- To investigate the effects of anti-CD11b/CD18 antibodies, HDL3, and low-density lipoprotein (LDL) on monocyte fibrinogen binding.
- To explore a novel mechanism for HDL's potential role in preventing arteriosclerosis.
Main Methods:
- Monocytes were activated using adenosine diphosphate (ADP) or Cytochalasin-B.
- Fibrinogen binding was measured in the presence of anti-CD11b/CD18 antibodies, HDL3, or LDL.
- Monocyte binding of anti-CD11b/CD18 antibodies was assessed after incubation with HDL3 or LDL.
Main Results:
- Anti-CD11b and anti-CD18 antibodies significantly reduced fibrinogen binding on ADP-activated monocytes.
- HDL3 significantly lowered fibrinogen binding on ADP-activated monocytes but not on Cytochalasin-B-activated monocytes.
- LDL showed a slight, non-significant stimulatory effect on fibrinogen binding on ADP-activated monocytes.
Conclusions:
- HDL3's inhibition of fibrinogen binding on monocytes is a novel finding.
- This inhibition may impair monocyte recruitment and foam cell formation, suggesting a protective mechanism against arteriosclerosis.
- The study highlights a potential new pathway through which HDL may prevent the development of atherosclerosis.
Abstract:
High levels of fibrinogen and low levels of high-density lipoprotein (HDL) cholesterol were reported to be risk factors for coronary heart disease. CD11b/CD18, a fibrinogen-binding protein, is expressed on the surface of monocytes, which play a crucial role in the formation of atherosclerotic lesions. In the present study, we investigate the effects of antibodies against CD11b and CD18, as well as HDL3 and low-density lipoprotein (LDL) cholesterol on fibrinogen binding on monocytes. We find that binding of fibrinogen on monocytes activated with adenosine diphosphate (ADP) was reduced to 66.0+/-8.3% (mean +/- SD) in the presence of anti-CD11b antibodies (12.5 microg/ml; P < or = 0.02) and to 54.5+/-4.9% in the presence of anti-CD18 antibodies (20 microg/ml; P < or = 0.01), respectively. Fibrinogen binding on Cytochalasin-B-activated monocytes was reduced to 79.8+/-6.0% in the presence of anti-CD18 (20 microg/ml; P < or = 0.05). Incubation of ADP-activated monocytes with HDL3 (0.5 g/l) led to a lowering of fibrinogen binding to 65.0+/-6.6% (P < or = 0.05). No effect of HDL3 on fibrinogen binding was seen on Cytochalasin-B-activated monocytes. A slight, non-significant stimulatory effect of LDL on fibrinogen binding on ADP-activated but not on Cytochalasin-B-activated monocytes was additionally observed. Neither incubation with HDL3 or with LDL had a significant influence on ADP-activated cellular binding of anti-CD11b or anti-CD18 antibodies. The inhibition of fibrinogen binding on monocytes in the presence of HDL3 is a major new finding of this study. Since inhibition of fibrinogen binding in the presence of HDL might impair both monocyte recruitment to the arterial wall and foam cells formation, our findings suggests a novel mechanism by which HDL may prevent development of arteriosclerosis.