Selected matrix metalloproteinases activity and hypertension-mediated organ damage in relation to uric acid serum level

Abstract

Background: Atherosclerosis is as a systemic inflammatory disease associated with the activation of many mediators, including matrix metalloproteinases (MMPs), and may be amplified by abnormal high serum uric acid (UA) concentration (hyperuricemia, HU). The aim of the study was to determine the relationship between serum UA concentration and activity of MMPs and their correlation with the hypertension-mediated organ damage (HMOD) intensity. Methods: One hundred and nine patients untreated with antihypertensive, hypolipemic or uratelowering drugs with diagnosed stage 1-2 essential hypertension were included in this study. In all participants blood pressure (BP) was measured, carotid-femoral pulse wave velocity (PWV), intima-media thickness (IMT), echocardiography and blood tests including UA, lipids and serum concentrations of MMPs (1, 2, 3, 9) were observed. The participants were divided into hyper-and normuricemic groups. Results: Uric acid concentration in the whole study group positively correlated with some HMOD parameters (IMT, PWV, left ventricular mass index, left atrial dimension). Among the studied metalloproteinases only MMP-3 activity positively correlated with serum UA concentration independently of age, body mass index and serum lipids (R2 = 0.11, p = 0.048). Multivariate regression analysis showed positive association between IMT and BP, UA concentration and MMP-3 activity, independently of waist circumference and serum lipids (R2 = 0.328, p < 0.002). Patients with HU were characterized by higher activity of MMP-3 than those without (19.41 [14.45; 21.74] vs. 13.98 [9.52; 18.97] ng/mL, p = 0.016). Conclusions: The present results may support the thesis that UA and the increased by UA activity of MMPs may take part in the development of HMOD, especially IMT.

Matrix Metalloproteinases and Their Role in Mechanisms Underlying Effects of Quercetin on Heart Function in Aged Zucker Diabetic Fatty Rats

“…Higher serum UA concentrations were found to be associated with higher mean arterial pressure and hypertension [39] as well as with an increased risk of type 2 diabetes [40]. A possible positive relation of serum uric acid to MMPs [41,42] as well as negative correlation between SOD and uric acid were documented. It has been found that decreased levels of antioxidants such as SOD in plasma and tissues are associated with increased UA levels in blood circulation [43].…”

Effects of uric acid-lowering therapy in patients with essential arterial hypertension

“…In our opinion, patients with potentially reversible cardiovascular changes are most likely to receive the greatest benefits from intensive ULT used in parallel with the modification of other cardiovascular risk factors as part of primary prevention of ischemic heart disease. We have previously shown that a higher UA concentration via higher serum matrix metalloproteinase (MMP) 3 enhances selected HMOD, especially carotid IMT in patients with AH [37]. Extracellular MMPs are part of inflammation leading to the degradation of collagen, vessel remodeling and atherosclerotic plaque rupture [38,39].…”

Effects of Uric Acid Lowering Therapy in Patients With Essential Arterial Hypertension

“…In our opinion patients with potentially reversible cardiovascular changes are most likely to receive the greatest bene ts from intensive ULT used in parallel with the modi cation of other cardiovascular risk factors as part of primary prevention of ischemic heart disease. We have previously shown that a higher UA concentration via higher serum matrix metalloproteinase (MMP) 3 enhances selected HMOD, especially carotid IMT in patients with AH [37]. Extracellular MMPs are part of in ammation leading to the degradation of collagen, vessel remodelling and atherosclerotic plaque rupture [38,39].…”