Markers of Collagen Degradation in Remodeling and Diastolic Dysfunction of Left Ventricle in Patients with Arterial Hypertension

M. Shambatov, N. V. Izmozherova, A. A. Popov, I. Grishina, E. V. Kudryavtseva, V. Bazarnyi, L. Polushina, M. Kopenkin
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Abstract

Introduction. Myocardial remodeling is a consequence or predictor of several cardiovascular diseases. The key process in myocardial remodeling is the degradation of collagen fibers, mediated by the activity of matrix metalloproteinases and their tissue inhibitor.The aim of this study was to evaluate serum levels of matrix metalloproteinase type 9 and tissue inhibitor of matrix metalloproteinase type 1 in female patients with arterial hypertension, myocardial remodeling, and diastolic dysfunction.Materials and methods. A cross-sectional study that included 84 postmenopausal women. All patients underwent echocardiography. Left ventricular remodeling was assessed according to Ganau classification, and diastolic function was evaluated using transmittal flow parameters. Serum analysis included the determination of MMP-9 and TIMP-1 levels using an enzyme-linked immunosorbent assay.Results. The median concentration of MMP-9 in the sample was 2 295.00 (923.60–4 114.00) ng/ml, TIMP — 1–17 010.00 (16 780.00–17 170.00) ng/ml. When evaluating the echocardiographic parameters of the patients included in the study, changes were revealed that indicate structural and functional remodeling of the LV and DD. 29 patients (35 %) had normal geometry, 6 patients (7 %) had concentric myocardial remodeling, 21 patients (25 %) had concentric myocardial hypertrophy, 28 cases (33 %) had eccentric myocardial hypertrophy. Statistically significant changes in the activity of MMP-9 and TIMP-1 were revealed in patients with various structural and geometric variants of remodeling. DD was detected in all patients included in the study: I degree was detected in 25 patients (30 %), II degree was determined in 59 cases (70 %). Using one-way analysis of variance, statistically significant differences in the level of MMP-9 in patients with grades I and II DD were determined. MMP-9 and MMP-9/TIMP-1 in patients with grade II DD are significantly higher than in patients with grade I.Discussion. Under pathophysiological conditions, the proteolytic properties of MMP-9 contribute to the stimulation of the immune response, initiating pathogenesis and aggravating the progression of the disease. Evaluation of the activity of MMP-9 and TIMP-1 in patients with arterial hypertension may be a marker of myocardial remodeling.Conclusion. An increase in the activity of matrix metalloproteinase type 9 and a decrease in the activity of a tissue inhibitor of matrix metalloproteinases type 1 were revealed in patients with arterial hypertension, myocardial remodeling and LV diastolic dysfunction. The level of MMP-9 is associated with the degree of diastolic dysfunction and the structural-geometric type of LV remodeling.
动脉高血压患者左心室重塑和舒张功能障碍中的胶原降解标志物
导言心肌重塑是多种心血管疾病的后果或预兆。本研究旨在评估动脉高血压、心肌重塑和舒张功能障碍女性患者血清中基质金属蛋白酶 9 型和基质金属蛋白酶 1 型组织抑制剂的水平。这是一项横断面研究,包括 84 名绝经后女性。所有患者均接受了超声心动图检查。根据加瑙分类法评估左心室重塑情况,并使用透射血流参数评估舒张功能。血清分析包括使用酶联免疫吸附试验测定 MMP-9 和 TIMP-1 的水平。样本中 MMP-9 的中位浓度为 2 295.00 (923.60-4 114.00) 纳克/毫升,TIMP-1-17010.00 (16 780.00-17 170.00) 纳克/毫升。在评估研究对象的超声心动图参数时,发现了一些变化,表明左心室和右心室的结构和功能发生了重塑。29例患者(35%)几何形状正常,6例患者(7%)有同心心肌重塑,21例患者(25%)有同心心肌肥厚,28例患者(33%)有偏心心肌肥厚。在各种结构和几何变异的重塑患者中,MMP-9 和 TIMP-1 的活性发生了统计学意义上的重大变化。研究中的所有患者都检测到了 DD:25名患者(30%)检测出Ⅰ度DD,59名患者(70%)检测出Ⅱ度DD。通过单因素方差分析,确定了 I 级和 II 级 DD 患者的 MMP-9 水平存在显著的统计学差异。II级DD患者的MMP-9和MMP-9/TIMP-1明显高于I级患者。在病理生理学条件下,MMP-9 的蛋白水解特性有助于刺激免疫反应,启动发病机制并加剧疾病进展。评估动脉高血压患者体内 MMP-9 和 TIMP-1 的活性可能是心肌重塑的标志。结论:在动脉高血压、心肌重塑和左心室舒张功能障碍患者中,基质金属蛋白酶9型的活性增加,基质金属蛋白酶1型组织抑制剂的活性降低。MMP-9 的水平与舒张功能障碍的程度和左心室重塑的结构-几何类型有关。
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