1. THE ROLE OF OXIDATIVE STRESS IN CALCIFIC AORTIC VALVE STENOSIS PATIENTS
Juris Hofmanis1, Dace Hofmane2, Gita Gersone3, Simons Svirskis4, Vitolds Mackevics1, Peteris Tretjakovs3, Aivars Lejnieks1
1 Department of Internal Diseases, Faculty of Medicine, Riga Stradins University, Riga, Latvia
2 Zemgale Health Centre, Jelgava, Latvia
3 Department of Human Physiology and Biochemistry, Faculty of Medicine, Riga Stradins University, Riga, Latvia
4 Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia
Interactions between reactive O2 species (ROS), endothelium and antioxidants are important in the development process of aortic valve stenosis (AoS).
Superoxide (one of the most active ROS molecules) inactivates nitric oxide (NO) and promotes endothelial dysfunction.
The aim of the study is to analyze thioredoxin reductase 1 (TrxR1) and mieloperoxidase (MPO) plasma levels in the control and stenosis groups.
The main role of TrxR1 is to reduce inflammation, proliferation, apoptosis, thus reducing the osteogenic transformation of the valve's interstitial cells.
As a pro-oxidant, MPO is associated with both inflammation and oxidative stress.
TrxR1 were significantly higher in patients than in control group (p=0.0016).
TrxR1 had the highest levels in patients with mild (p=0.0001) and severe stenosis (p=0.039).
A statistically significant positive relationship between TrxR1 and chemerin was found by linear regression analysis (p=0.006; rp=0.32).
TrxR1 also correlated with FGF-21 (p=0.031; rp=0.25) and with MMP-3 (p=0.013; rp=0.37).
MPO level increased along with stenosis severity, compared with the control group (p0,02 in the mild stenosis group; p0,001 in the moderate stenosis and p0,0007 in the severe stenosis group).
MPO correlated with chemerin (p=0.0057; rp=0.32) and with MMP-9 (p=0.007; rp=0.4).
We found statistically significant negative correlation between MPO and HDL-H (p=0.047; rp= -0.3).
Statistically significantly positive correlation between TrxR1 and MPO was found (p=0.008; rp=0.30).
52 AoS patients were included in the study (18 mild, 19 moderate, 15 severe stenosis) and 50 healthy subjects selected as control. Stenosis patients were divided into severity subgroups according to EchoKG: severe (Vmax >4 m/s; PG >40 mmHg; AVA <1.0 cm2; indexed AVA <0.6); moderate (Vmax m/s; PG mmHg; AVA cm2; indexed AVA ); mild (Vmax m/s; PG <20 mmHg; AVA 1.5 cm2; indexed AVA 0.85. TrxR1, MPO, MMP-3, MMP-9 detected by ELISA; HDL-H with standard method.
AoS is associated with increased TrxR1 and MPO. Oxidative stress is associated with stenosis in all severity degrees.
Higher levels of oxidative stress in severe aortic stenosis than in the moderate stenosis we relate to the continuation of both oxidative stress as well as that the most of the severe stenosis patients have developed complications such as left ventricular hypertrophy and chronic heart failure.
Oxidative stress and inflammation are interrelated processes, reflected by chemerin, which is an inflammatory cytokine and a good diagnostic marker for mild aortic stenosis, its relation with TrxR1 and MPO.
The negative correlation of MPO with HDL-C shows the effect of oxidative stress on lipid metabolism, leading to HDL-C dysfunction and oxHDL-C formation.
Chemerin relation to TrxR1 and MPO as well as their role in the pathogenesis of oxidative stress and inflammation shows, that in patients with aortic stenosis, chemerin is an inflammatory cytokine.