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Published on: June 2, 2022
Association of Matrix Metalloproteinases with Coronary Artery Calcification in Patients with CHD
Yana V Polonskaya1, Elena V Kashtanova1, Ivan S Murashov2
1Research Institute of Internal and Preventive Medicine-Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (IIPM-Branch of IC&G SB RAS), 175/1 B. Bogatkova Str., 630089 Novosibirsk, Russia.
Insights
Matrix metalloproteinases (MMPs) are linked to coronary artery calcification. MMP-9 showed a significant association with calcification risk, suggesting MMPs
Area of Science:
- Cardiovascular Biology
- Biochemistry
- Medical Research
Background:
- Coronary artery calcification (CAC) is a significant indicator of cardiovascular disease.
- The role of matrix metalloproteinases (MMPs) in the pathogenesis of atherosclerosis and vascular calcification is not fully understood.
Purpose of the Study:
- To investigate the association between serum and vascular levels of various matrix metalloproteinases (MMPs) and coronary artery calcification (CAC) in patients with and without coronary heart disease (CHD).
- To explore the potential of specific MMPs as biomarkers for CHD and CAC.
Main Methods:
- Serum and coronary artery samples were collected from 78 patients with CHD and 36 controls.
- Serum MMP levels (MMP-1, -2, -3, -7, -9, -10, -12, -13) were measured using multiplex analysis.
- Vascular MMP levels (MMP-1, -3, -7, -9) and MMP-9 expression were assessed via enzyme immunoassay and immunohistochemistry, respectively.
- Associations between MMP levels, calcium content, and other biomarkers (osteoprotegerin, osteonectin, osteocalcin, osteopontin) were analyzed.
Main Results:
- Patients with CHD exhibited elevated serum levels of MMP-1, MMP-7, and MMP-12 compared to controls.
- Serum MMP-1 and MMP-3 levels correlated with calcium content in coronary arteries.
- MMP-9 expression was significantly higher in calcified plaques compared to non-calcified ones.
- MMP-9 was strongly associated with an increased relative risk of coronary artery calcification, confirmed by immunohistochemistry.
Conclusions:
- Specific matrix metalloproteinases, particularly MMP-9, play a role in the process of coronary artery calcification.
- MMP-1, MMP-7, and MMP-12 show potential as biomarkers for identifying coronary heart disease.
Abstract:
This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary heart disease (CHD) and 36 without CHD. Blood and samples of coronary arteries obtained as a result of endarterectomy were examined. Serum levels of metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13 were determined by multiplex analysis. In blood vessel samples, MMP-1, MMP-3, MMP-7, and MMP-9 were determined by enzyme immunoassay; MMP-9 expression was evaluated by immunohistochemistry. Patients with CHD had higher serum levels of MMP-1, MMP-7, and MMP-12. Blood levels of MMP-1 and MMP-3 were associated with calcium levels, MMP-9 with osteoprotegerin and osteonectin, MMP-7 and MMP-10 with osteoprotegerin, MMP-12 with osteocalcin, and MMP-13 with osteopontin. Calcified plaques had higher levels of MMP-1 and MMP-9 compared to plaques without calcification. The relative risk of coronary arteries calcification was associated with MMP-9, which is confirmed by the results of immunohistochemistry. The results obtained indicate the participation of some MMPs, and especially MMP-9, in the calcification processes. The study can serve as a basis for the further study of the possibility of using MMP-1, MMP-7 and MMP-12 as potential biomarkers of CHD.
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