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Decreased mitogenic activity in hypercholesterolaemic plasma
J Mölgaard1, M Carlsson, J Nilsson
1Department of Internal Medicine, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
Insights
Plasma from hypercholesterolaemia patients showed lower mitogenic activity on smooth muscle cells. Simvastatin treatment normalized this activity, suggesting cholesterol
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Cellular Signaling
Background:
- Hypercholesterolaemia is a risk factor for cardiovascular disease.
- Smooth muscle cell proliferation contributes to atherosclerosis.
- The mitogenic effects of plasma in hypercholesterolaemia are not fully understood.
Purpose of the Study:
- To compare the mitogenic activity of plasma from hypercholesterolaemic patients versus controls.
- To investigate the effect of simvastatin on plasma mitogenic activity.
Main Methods:
- Rat aortic smooth muscle cells were used.
- DNA synthesis was measured by 3H-thymidine incorporation.
- Plasma lipid profiles were analyzed before and after simvastatin treatment.
Main Results:
- Hyperlipidaemic plasma exhibited significantly lower mitogenic activity (25.7%) compared to normocholesterolaemic plasma (32.0%).
- Simvastatin treatment reduced cholesterol and apolipoprotein B levels in hyperlipidaemic patients.
- Post-treatment plasma mitogenic activity in hyperlipidaemic patients normalized to 32.3%.
Conclusions:
- Unexpectedly, hyperlipidaemic plasma has reduced mitogenic activity on smooth muscle cells.
- Lowering cholesterol with simvastatin normalizes this reduced mitogenic activity.
- The underlying mechanisms for these findings require further investigation.
Abstract:
The mitogenic activity on rat aortic smooth muscle cells of plasma from patients with hypercholesterolaemia was compared to that of plasma from a normocholesterolaemic control group and to that obtained after lowering plasma cholesterol levels in the hypercholesterolaemic groups with simvastatin. Mean plasma total and low density lipoprotein cholesterol and apolipoprotein B concentrations in the two groups were 8.62 +/- 0.62 mmol l-1, 7.03 +/- 0.56 mmol l-1 and 1.96 +/- 0.14 g l-1, respectively, and 5.05 +/- 0.20 mmol l-1, 3.42 +/- 0.18 mmol l-1 and 0.80 +/- 0.04 g l-1, respectively, all differences significant at P less than 0.001. During simvastatin treatment these parameters decreased to 5.70 +/- 0.35, 4.15 +/- 0.33 mmol l-1 and 1.33 +/- 0.08 g l-1, all changes being significantly (P less than 0.001) lower than before treatment. Hyperlipidaemic plasma in untreated patients had a significantly lower mitogenic activity than normolipidaemic control plasma as measured by autoradiographic labelling of DNA after 3H-thymidine incorporation, 25.7 +/- 1.8% vs. 32.0 +/- 1.9%, P less than 0.05. Lowering plasma cholesterol levels in the hyperlipidaemic patients 'normalized' the mitogenic activity to 32.3 +/- 1.6%, P less than 0.05. The reason for this unexpected finding is not known.