Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia
Cristina Barale1, Chiara Frascaroli2, Rouslan Senkeev1
1Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Insights
Simvastatin significantly reduced platelet activation, inflammation, and endothelial dysfunction in hypercholesterolemic patients. Lowering LDL-cholesterol was key, but other simvastatin effects also combat atherosclerosis progression.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Biochemistry
Background:
- Statins offer lipid-lowering effects and slow atherosclerosis via anti-inflammatory and platelet-inhibiting actions.
- Investigated the correlation between simvastatin's platelet inhibition and its effects on lipids, inflammation, oxidative stress, and endothelial/platelet activation.
Purpose of the Study:
- To determine if simvastatin's anti-platelet effects correlate with its impact on lipid profiles, inflammation, oxidative stress, and endothelial/platelet activation markers.
- To explore the relationship between LDL-cholesterol levels and various markers of platelet reactivity and inflammation.
Main Methods:
- Hypercholesterolemic patients received diet or diet plus simvastatin (40 mg) for 2 months.
- Assessed platelet aggregation, aspirin's effect, inflammatory/endothelial/platelet activation markers, and oxidative stress (8-OH-2'-deoxyguanosine).
Main Results:
- Simvastatin improved lipid profiles and reduced platelet aggregation to ADP, collagen, and arachidonic acid (AA).
- Circulating levels of IL-6, IL-13, IFN-γ, VEGF, sE-selectin, sCD-40L, sP-selectin, and 8-OH-2'-deoxyguanosine decreased; IL-10 and sRAGE increased.
- LDL-cholesterol positively correlated with inflammatory markers and platelet aggregation, and negatively with IL-10 and sRAGE.
Conclusions:
- Simvastatin treatment in hypercholesterolemia reduces platelet activation, subclinical inflammation, and endothelial dysfunction.
- While LDL-cholesterol is a primary correlate of platelet reactivity, other statin mechanisms likely contribute to inhibiting atherosclerosis progression.
Background:
Beside the lipid-lowering effect, statins slow the progression of atherosclerosis by exerting anti-inflammatory and platelet inhibiting effects. We investigated whether platelet inhibition by simvastatin correlates with the statin effects on lipid lowering, inflammation, oxidative stress, and endothelial and platelet activation.
Methods:
In hypercholesterolemic patients allocated to diet (n=20) or a 2-month treatment with diet plus 40 mg simvastatin (n=25), we evaluated platelet aggregating responses to ADP, collagen, and arachidonic acid (AA), the effect of aspirin on AA-induced aggregation, pro- and anti-inflammatory and atherogenic mediators (IL-1β, -5, -6, -7, -8, -9, -10, -12, and -13, IFN-γ, IP-10, Eotaxin, and sRAGE), markers of endothelium (sE-selectin, VEGF, and MCP-1) and platelet activation (sP-selectin, sCD-40L, RANTES, and PDGF-bb), and oxidative stress (8-OH-2'-deoxyguanosine).
Results:
After treatment, beside the improvement of lipid profile, we observed the following: a reduction of platelet aggregation to ADP (p=0.0001), collagen (p=0.0001), AA (p=0.003); an increased antiaggregating effect of aspirin in the presence of AA (p=0.0001); a reduction of circulating levels of IL-6 (p=0.0034), IL-13 (p<0.0001), IFN-γ (p<0.0001), VEGF (p<0.0001), sE-selectin (p<0.0001), sCD-40L (p<0.0001), sP-selectin (p=0.003), and 8-OH-2'-deoxyguanosine (p<0.0001); an increase of IL-10 and sRAGEs (p=0.0001 for both). LDL-cholesterol levels (i) positively correlated with IL-6, IFN-γ, E-selectin, sCD-40L, 8-OH-2'-deoxyguanosine, platelet aggregation to ADP, collagen, AA, and aspirin IC-50 and (ii) negatively correlated with IL-10 and sRAGE. In multiple regression analyses, LDL-cholesterol was the strongest predictor for most parameters of platelet reactivity.
Conclusion:
In primary hypercholesterolemia, simvastatin treatment reduced platelet activation and subclinical inflammation and improved endothelial dysfunction. LDL-cholesterol levels were the major correlate of platelet reactivity; however, other effects of statins may contribute to reducing the progression of atherosclerosis.
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