Impact of several proinflammatory and cell degradation factors in patients with aortic valve stenosis

Abstract

Aortic valve (AoV) stenosis is the third most common cardiovascular disease. The pathogenesis of AoV stenosis is associated with an inflammatory process where MMPs serve important roles. The aim of the present study was to determine the association between matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and inflammatory factors, and AoV stenosis at various degrees of severity compared with the control. A total of 18 patients with mild, 19 with moderate and 15 with severe AoV stenosis were included in the present stud, and 50 individuals were enrolled in the control group. The severity of stenosis was determined by echocardiography. The expression levels of chemerin, fibroblast growth factor 21, MMP‑1, ‑3, and ‑9, and TIMP‑1 and ‑3 were analyzed by ELISA. Data were analyzed using GraphPad Prism7 software. The expression levels of MMP‑1 was increased in patients with stenosis compared with the control group (P=0.0043). Distribution of the trimodal MMP‑1 values was obtained in the stenosis group and monomodal in the control group. A total of 80% of patients in the stenosis group presented significantly increased expression levels of MMP‑1 compared with the control group (P=0.0002). Expression of MMP‑1 was significantly higher in all stenosis groups compared with the control. The highest expression level of MMP‑1 appeared in patients with moderate stenosis (P<0.0001). There was no significant difference in the expression of MMP‑3, MMP‑9 and TIMP‑1 in the aortic stenosis group, compared with the control group. A positive correlation between MMP‑1 and MMP‑9 expression levels was identified (r=0.37; P=0.017). The increase of MMP‑1 was correlated with the increase of MMP‑9, but not with the level of MMP‑3. The expression levels of chemerin was significantly elevated in patients with stenosis compared with healthy patients. The highest expression levels of chemerin were determined in patients with mild (P=0.0001) and moderate (P=0.0007) stenosis and decreased with the grade of severity compared with the control group. The expression of FGF‑21 was significantly different between the control and mild (P=0.013), moderate (P=0.015) and severe stenosis (P=0.003) groups. The expression levels of FGF‑21 increased with the increase in severity grade, reaching the maximum for severe stenosis. The results of the present study indicated that the inflammatory process is predominantly occurring at the early, mild stage of stenosis and the most prominent extracellular matrix remodeling occurs in moderate stenosis (demonstrated by MMP‑1 levels). In patients with severe stenosis, the levels of MMP‑1 and chemerin (which are lower than in a case of mild or moderate stenosis) could indicate the development of calcinosis and the reduction in activity or inactivation of the inflammatory process.