Activity of matrix metalloproteinase type 9 and its relationship with calcification of the thoracic aorta in patients with resistant hypertension: cross-sectional comparative study

Abstract

Background. The extracellular matrix of vessels is degraded under the influence of matrix metalloproteinases (MMPs). MMP type 9 is of particular interest in arterial hypertension (AH) since its activity is regulated by a tissue inhibitor of matrix metalloproteinase type 1 (TIMP1). The balance of their ratio can shift in either direction depending on the disease stage and provoke vascular wall calcification. Objective. This cross-sectional comparative study investigated the level of MMP9 and its type 1 tissue inhibitor and their relationship with the severity of thoracic aorta calcification in patients with resistant hypertension, depending on antihypertensive therapy effectiveness. Material and methods. The study included 92 patients with resistant hypertension. All patients underwent 24-hour blood (BP) pressure monitoring (ABPM), and had their index of the thoracic aorta (ТАС) and the plasma levels of MMP9 and TIMP1 assessed. Results. Patients were divided into groups based on whether they achieved the BP target level according to the results of ABPM: controlled (n=44) and uncontrolled (n=48) resistant AH. In the second group, most estimated parameters of ABPM were higher, and the variants of the daily BP profile for non-dipper and night-peaker systolic blood pressure (SBP) were more common than in the first group. In the second group, a more pronounced increase in TAC, TIMP1, and TIMP1/MMP9 levels was revealed. Evaluation of the relationship between the studied parameters revealed a positive relationship between TAC and age (r=0.683, p 0.00001), hypertension duration (r=0.610, p 0.00001) and a negative relationship with regular antihypertensive therapy duration (r=0.822, p 0.00001). ТАC was higher in individuals with higher values of SBP (r=0.513, р 0.00001), pulse BP (r=0.805, р 0.00001), rate of morning rise in BP (r=0.678, р 0.00001) and insufficient decrease in SBP at night (r=-0.822, р 0.00001). There was a positive correlation of moderate strength TAC with the level of low-density lipoproteins (r=0.490, p=0.0002), TIMP1 (r=0.344, p=0.005) and the TIMP1/MMP9 ratio (r=0.481, p 0.00001). Conclusion. In patients with resistant hypertension, an increase in the TAC was revealed, which has a statistically significant direct correlation with the value of pulse BP, the morning rise in BP, and an insufficient decrease in SBP at night. An imbalance in the TIMP1/MMP9 ratio, rather than an isolated increase in MMP9, can indicate the intensity of the formation and degradation of the extracellular matrix components in patients with resistant AH, which triggers the vascular wall calcification process.