Abstract
Background Arterial hypertension (HT) is a serious and prevalent epidemiological factor in the development of coronary artery disease (CAD). Metalloproteinases (MMPs), especially MMP-2 and MMP-9, and their natural endogenous tissue inhibitors (TIMPs) are involved in the pathogenesis of HT and its complications. MMPs are also involved in the development of diabetes (DM), a risk factor for CAD. The aim of the study was to explore the influence of CAD, HT, and DM on changes in plasma levels of MMP-2 and MMP-9 and their inhibitor TIMP-4. Methods and Results The study involved 70 patients with stable CAD admitted for coronary angiography and 15 healthy subjects. Whole blood samples were collected prior to angiography. MMP-2, MMP-9, and TIMP-4 levels in plasma were estimated using ELISA tests. CAD patients showed a significantly increased level of TIMP-4 and decreased level of MMP-2 in comparison to healthy controls (p=0.011 and p=0.037, respectively). Concentration of MMP-2, MMP-9, and TIMP-4 did not differ in the group with and without hypertension. Patients with DM presented higher MMP-2 level than patients without DM (p < 0.001). Multiple regression analysis of the influence of independent variables such as CAD stage, DM, and HT on MMP-2, MMP-9, and TIMP-4 showed that only DM was independently associated with a higher level of MMP-2 (β = 0.42, R2 = 0.17, p < 0.001). Conclusion Data showed that patients with CAD presented higher TIMP-4 and lower MMP-2 concentration regardless of HT and DM. HT had no effect on MMP-2, MMP-9, and TIMP-4 levels in serum. DM was independently associated with higher MMP-2 concentration; however, co-occurrence of CAD and DM was associated with the balance in the MMP-2 level. Concentration of MMP-9 did not change significantly in any of the analysed groups.
Highlights
Coronary heart disease is a condition of myocardial ischemia associated with changes in coronary arteries
We suggest that the increased production of matrix metalloproteinases (MMPs), due to the mechanical stress induced by hypertension, should be accompanied by an increased expression of TIMP-4 [26]. is study may serve as a preliminary test to determine whether TIMP inhibition of MMPs may help with the prevention of cardiovascular complications resulting from the coexistence of hypertension, diabetes, and coronary artery disease
MMP-2 and MMP-9 are released from inflammatory cells, which means that their level in the circulation increases during inflammation [6, 29]. ese two MMPs were found in vascular smooth muscle cells (VSMC), in which both indicate that they can affect the development of atherosclerosis and atherosclerotic plaque rupture [26, 30]. e balance between MMPs and TIMPs is very important; it gets unstable in chronic remodeling processes, e.g., as a result of myocardial infarction and heart failure [31]
Summary
Coronary heart disease is a condition of myocardial ischemia associated with changes in coronary arteries. E aim of the study was to explore the influence of CAD, HT, and DM on changes in plasma levels of MMP-2 and MMP-9 and their inhibitor TIMP-4. E study involved 70 patients with stable CAD admitted for coronary angiography and 15 healthy subjects. Multiple regression analysis of the influence of independent variables such as CAD stage, DM, and HT on MMP-2, MMP-9, and TIMP-4 showed that only DM was independently associated with a higher level of MMP-2 (β 0.42, R2 0.17, p < 0.001). Data showed that patients with CAD presented higher TIMP-4 and lower MMP-2 concentration regardless of HT and DM. DM was independently associated with higher MMP-2 concentration; co-occurrence of CAD and DM was associated with the balance in the MMP-2 level. Concentration of MMP-9 did not change significantly in any of the analysed groups
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