Activity of matrix proteinases and their inhibitors in patients with thoracic aortic dissection

Abstract

Purpose. To study changes in profibrogenic mediators in patients with thoracic aortic dissection.Material and methods. The study was carried out in 66 patients with dissection of the ascending aneurysm and the aortic arch, which occurred against the background of atherosclerosis and hypertension, aged 48 to 73 years. According to the objectives of the study, the patients were divided into three groups: the first – 32 patients with acute dissections, the second – 34 patients with subacute and chronic dissections, the third – 30 patients with aneurysms of the thoracic and abdominal aorta, who were diagnosed during a routine examination. The control was the results of laboratory studies obtained in 28 healthy volunteers. The study groups were randomized according to the main clinical criteria and the severity of the condition (χ2 = 0.901, p = 1.000). The standard of laboratory tests included a clinical and biochemical blood test, a blood test for troponin I, a blood clotting test, a general urine test, and the calculation of GFR. Determined the blood group, Rh factor. On a mandatory basis, the patients were examined for the presence of the Australian antigen, antibodies to viral hepatitis "C", the Wasserman reaction was performed, and the presence of HIV infection was examined. Determination of the level of MMP-9, its inhibitor TIMP-2 and a complex with an inhibitor (MMP-9/TIMP-2) in the blood serum were investigated using commercial diagnostic kits from R&D Diagnostics Inc. (USA): Human MMP-9 Quantikine ELISA Kit, Cat.GA30092; Human ТІМP-2 Quantikine ELISA Kit, Cat. BE69073). Statistical analysis of the data obtained was carried out on an IBM PC Intel Core i5-6500U personal computer with MS Windows 10 using the STATISTICA 10.0 program (StatSoft, Inc.).Results. In all types of aortic aneurysms (uncomplicated and complicated), an increase in the level of MMP-9 was noted concerning the control values: in patients of the 1st group, the level of MMP-9 was increased on average by 284.5%, in the 2nd group - by 176, 9% and in patients with uncomplicated aneurysms - by 91.7%, respectively, to the control values (p <0.05). At the same time, the level of MMP-2 was increased in all the studied groups but did not differ significantly between the groups (p = 0.37). The concentration of tissue inhibitor of matrix metalloproteinases (TIMP-2) in patients with acute dissection of the aortic aneurysm was on average 40.4% higher than the control values (p <0.001); in patients with chronic dissection of the aneurysm, the differences were insignificant; and in patients with uncomplicated aortic aneurysms, the level of TIMP-2 was, on average, 12% lower than that obtained in the control group (p <0.05). With a confidence level of 0.95% (p <0.05), the MMP-9 index significantly differed in all three groups. The MMP-9/TIMP-2 coefficient (inhibition coefficient according to MMP-9) was higher in patients with complicated aneurysms and amounted to 0.67, respectively (in the control – 0.25) (p <0.001). In patients with uncomplicated aneurysms, this integral indicator was lower than in the first two groups but exceeded the indicators of the control group by 112% (p <0.001). With the progression of degenerative changes in the middle lining of the vessel, MMP-9 and TIMP-2 decreased compared with patients with uncomplicated aneurysm and chronic dissection.Conclusions. Severe course of acute aortic dissection is associated with the presence of high MMP-9 levels, while SMC disorders occur against the background of oxidative stress and an imbalance between pro-inflammatory and anti-inflammatory cytokines are associated with inhibition of TIMP-2. In various types of complicated aortic aneurysms, there is an imbalance of MMP and their inhibitors, which affect the rate of proteolysis of extracellular matrix components with a predominance of the processes of their formation and accumulation.