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HDL-C Role in Acquired Aortic Valve Stenosis Patients and Its Relationship with Oxidative Stress
Juris Hofmanis1, Dace Hofmane2, Simons Svirskis3
1Faculty of Medicine, Department of Internal Diseases, Riga Stradins University and Riga East University Hospital, LV-1007 Riga, Latvia. jl.cardio@gmail.com.
Insights
High-density lipoprotein cholesterol (HDL-C) levels significantly decrease in aortic stenosis (AS) patients, correlating with oxidative stress markers like myeloperoxidase (MPO). This finding highlights HDL-C
Area of Science:
- Cardiovascular Research
- Biochemistry
- Oxidative Stress Biology
Background:
- Mechanical stress is a primary driver of calcific aortic stenosis (AS), leading to endothelial dysfunction and chronic inflammation.
- Oxidative stress, particularly dysfunction of high-density lipoprotein cholesterol (HDL-C), plays a crucial role in AS development.
- Understanding the interplay between HDL-C, oxidative stress biomarkers, and AS severity is vital for therapeutic strategies.
Purpose of the Study:
- To investigate the role of HDL-C in patients with varying degrees of AS.
- To assess the relationship between HDL-C levels and oxidative stress biomarkers, specifically thioredoxin reductase 1 (TrxR1) and myeloperoxidase (MPO).
Main Methods:
- Echocardiography was used to determine AS severity in 18 mild, 19 moderate, and 15 severe AS patients, compared to 50 controls.
- Serum levels of HDL-C were measured using commercial tests.
- Biomarkers TrxR1 and MPO were quantified via ELISA.
Main Results:
- HDL-C levels were significantly lower in all AS severity groups compared to controls, with a more pronounced decrease in women.
- Elevated TrxR1 levels were observed in mild and severe AS, though a direct correlation with HDL-C was not established.
- Myeloperoxidase (MPO) levels were elevated across all AS grades, and a negative correlation was found between MPO and HDL-C, indicating HDL-C dysfunction.
Conclusions:
- HDL-C levels are significantly associated with the development and progression of AS across all severity grades, particularly in women.
- The negative correlation between MPO and HDL-C, alongside increased TrxR1, suggests a strong link between HDL-C dysfunction and oxidative stress in AS patients.
Abstract:
Background and objectives: Mechanical stress is currently considered as the main factor promoting calcific aortic valve stenosis (AS) onset. It causes endothelial damage and dysfunction. The chronic inflammatory process causes oxidative stress. Oxidative stress-induced high-density lipoprotein cholesterol (HDL-C) dysfunction is an important component of the development of AS. The aim of the study was to evaluate the role of HDL-C in AS patients in three severity grades and in relation to the biomarkers of oxidative stress, thioredoxin reductase 1 (TrxR1) and myeloperoxidase (MPO). Materials and Methods: 18 patients with mild, 19 with moderate. and 15 with severe AS were included in the study, and 50 individuals were enrolled in the control group. Stenosis severity was determined by echocardiography. The TrxR1 and MPO were analyzed by ELISA, and HDL-C by commercially available tests. Data were analyzed using GraphPad Prism 8. Results: HDL-C in AS patients vs. control substantially decreases and this decline was observed in all three AS severity groups: mild (p = 0.018), moderate (p = 0.0002), and severe (p = 0.004). In both the control and the stenosis group, the HDL-C was higher in women than in men. In comparison to control, the HDL-C level was lower in the AS group, and more pronounced in women (p = 0.0001) than in men (p = 0.049). A higher TrxR1 level was observed in patients with mild (p = 0.0001) and severe AS (p = 0.047). However, a clear correlation between TrxR1 and HDL-C was not obtained. Analysis of MPO showed differences in all severity grades vs. control (p = 0.024 mild stenosis; p = 0.002 moderate stenosis; p = 0.0015 severe stenosis). A negative correlation (p = 0.047; rp = -0.28) was found between MPO and HDL-C, which confirms the adverse effects of MPO resulting in HDL-C dysfunction. Conclusions: In this study, we justified HDL-C level association with AS development process. The results unequivocally substantiated the association between HDL-C and AS in all severity grades in women, but only in moderate AS for men, which we explained by the small number of men in the groups. The obtained correlation between the HDL-C and MPO levels, as well as the concurrent decrease in the HDL-C level and increase in the TrxR1 level, indicate in general an HDL-C association with oxidative stress in AS patients.
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