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Matrix metalloproteinases in isolated hypercholesterolemia
1Third Department of Internal Medicine, General University Hospital and First School of Medicin, Charles University, Prague, Czech Republic. JMALI@LF1.CUNI.CZ
Aim:
Levels of circulating matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are altered in subjects with atherosclerosis. We hypothesized that also otherwise healthy hypercholesterolemic subjects will have altered MMP/TIMP concentrations. To validate this hypothesis, we compared MMPs/TIMPs in patients with moderate isolated hypercholesterolemia before and after atorvastatin therapy and in healthy normolipidemic controls.
Methods:
Twenty-seven otherwise healthy subjects with isolated hypercholesterolemia (total cholesterol 8.3+/-0.3 mmol/L) and 29 healthy normolipidemic controls were included. Patients were treated by atorvastatin for 10 weeks. We studied plasma levels of MMPs (MMP)-2, -3, and -9 and of their TIMPs (TIMP)-1 and -2.
Results:
Patients differed from controls by significantly lower MMP-3 [11.6 (5.7-21) vs 18.4 (12-22) ng/mL, P<10-4 (median, range 25-75%)] and TIMP-2 [13.3 (8.8-30.5) vs 22.1 (10.8-39) ng/mL, P=0.02] and by higher TIMP-1 [496 (461-538) vs 483 (456-500) ng/mL, P=0.004]. Atorvastatin decreased significantly TIMP-1 [from 496 (461-538) to 476 (451-525) ng/mL].
Conclusions:
Isolated hypercholesterolemia per se is associated with similar alterations of circulating MMPs and TIMPs as developed symptomatic atherosclerosis. Most consistent link to serum lipids was observed in case of TIMP-1. MMP and TIMP levels probably reflect the atherogenic process in its early stages in these subjects.
Insights
Isolated hypercholesterolemia alters matrix metalloproteinase (MMP) and tissue inhibitor (TIMP) levels, similar to atherosclerosis. Atorvastatin therapy reduced TIMP-1, suggesting these markers reflect early atherogenesis.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Molecular Biology
Background:
- Circulating matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs) are implicated in atherosclerosis.
- Altered MMP and TIMP levels are observed in symptomatic atherosclerosis.
- The role of MMPs/TIMPs in early-stage hypercholesterolemia is less understood.
Purpose of the Study:
- To investigate alterations in MMPs and TIMPs in hypercholesterolemic individuals.
- To compare MMP/TIMP concentrations in hypercholesterolemic patients versus healthy controls.
- To assess the effect of atorvastatin therapy on MMP/TIMP levels in hypercholesterolemia.
Main Methods:
- Studied 27 hypercholesterolemic patients and 29 normolipidemic controls.
- Measured plasma levels of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2.
- Hypercholesterolemic patients received atorvastatin for 10 weeks.
Main Results:
- Hypercholesterolemic patients had lower MMP-3 and TIMP-2, and higher TIMP-1 compared to controls.
- Atorvastatin therapy significantly reduced TIMP-1 levels.
- TIMP-1 showed the strongest correlation with serum lipids.
Conclusions:
- Isolated hypercholesterolemia is associated with MMP/TIMP alterations similar to symptomatic atherosclerosis.
- MMP and TIMP levels may indicate early-stage atherogenic processes.
- TIMP-1 is particularly linked to lipid levels in hypercholesterolemia.
