Relationship between the Levels of MMP-9, TIMP-1, and Zinc in Biological Samples of Patients with Carotid Atherosclerosis

Abstract

The aim our study was to evaluate the levels of zinc in blood serum, hair, and specimens of carotid artery atherosclerotic plaques (CAAPs) and their relationship to levels of MMP-9 and TIMP-1 in the serum of patients with stable and unstable CAAPs.Material and Methods: The study included 73 patients (55 men and 18 women) aged from 46 to 88 years (mean age 65.96±1.07 years) with CAAPs. The control group consisted of 10 healthy subjects of similar age and gender. The patients were divided into two groups depending on their atherosclerotic plaque stability according to prior duplex ultrasonography. Group 1 consisted of 45 patients with stable atherosclerotic plaque, and Group 2 included 28 patients with unstable AP. Patients with hemodynamically significant carotid stenosis and unstable atherosclerotic plaques underwent carotid endarterectomy. The serum concentration of MMP-9 and TIMP-1 was determined using the standard test systems for immunoassay. Quantitative determination of the zinc level in hair and atherosclerotic plaque was carried out by optical emission spectrometry; the serum Zn was determined colorimetrically.Results: The serum levels of MMP-9 and TIMP-1 were significantly higher in Group 2 compared to Group1 and the control group. The index of MMP-9/TIMP-1 was 1.6 times higher in Group 2 compared to the control group. The level of Zn in serum and hair was not significantly different between Groups 1 and 2. However, Zn levels in unstable atherosclerotic plaque were lower than in the control group. Reducing the concentration of zinc in the hair was accompanied by a decrease in zinc level in atherosclerotic plaque specimens. With the progression of atherosclerosis and increasing the intima-media thickness of the common carotid artery, the level of zinc in serum and atherosclerotic plaques decreased. Increasing the serum concentration of MMP-9 was accompanied by decreasing the zinc level in atherosclerotic plaque. High serum concentration of MMP-9 and TIMP-1, and MMP-9/TIMP-1 imbalance testify to CAAP instability.Keywords: carotid atherosclerosis; atherosclerotic plaque; matrix metalloproteinase-9 (MMP-9); TIMP metallopeptidase inhibitor 1; zinc.

Utility of Tissue Inhibitor Metalloproteinase-1 and Osteopontin as Prospective Biomarkers of Early Cardiovascular Complications in Type 2 Diabetes

“…TIMP-1 is a diagnostic marker for diabetes, in this study, the expression level of TIMP-1 was significantly increased in diabetic and cardiovascular diabetic patients than normal volunteers, also increased significantly in cardiovascular, diabetic patients than other diabetic groups, higher levels of circulating TIMP-1 was connected with the higher risk of diabetes and cardiovascular demise. This finding was consistent with Usmanova [ 20 ], furthermore, Lee and his colleagues who found that plasma TIMP-1 concentration was significantly raised in type II diabetic patients [ 21 ]. Also in this study, the TIMP-1 expression level was significantly higher in diabetic patients with cardiovascular diseases (CVD) than in those without cardiovascular diseases, these were in agreement with Papazafiropoulou and Tentolouris results [ 22 ].…”

Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism

“…Thus, they play an important role in immunity and angiogenesis, whereby their dysregulation may contribute to inflammation or atherosclerosis [ 42 , 43 ]. Jagadeesha et al [ 44 ] have reported that the activation of zinc-dependent endopeptidase MMP9 enables cell migration, while other authors have shown significant increasing of the MMP9 serum levels and lower zinc concentration in patients with unstable atherosclerotic plaque [ 45 ]. According to research, high MMP9 serum concentrations may increase the risk of atherosclerosis.…”

Low serum copper and zinc concentrations in North Indian children with overweight and obesit

“…Zinc regulates the proinflammatory cytokine expression [27], in which white adipose tissue produces interleukin-6 stimulating the secretion of CRP (C-reactive protein) in liver [28]. Zinc influences the expression of PPARs-α (peroxisome proliferator-activated receptors α), which plays a key role in the glucose and lipoprotein metabolism [29,30]. Zinc supplementation has been reported to decrease the total cholesterol, LDL cholesterol, and triglycerides and increase the HDL cholesterol [26,31].…”