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Published on: October 12, 2017
Measures of high-density lipoprotein function in men and women with severe aortic stenosis
Anouar Hafiane1, Elda Favari2, Anna E Bortnick3,4
1Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, 1001 Boulevard Decarie, Montreal, Québec, H3A 1A1, Canada. anouar.hafiane@mail.mcgill.ca.
Insights
Women with severe aortic stenosis have enhanced cholesterol efflux capacity, suggesting improved reverse cholesterol transport may protect against calcification. These sex-specific differences in high-density lipoprotein function offer insights into aortic valve calcification.
Area of Science:
- Cardiovascular Research
- Biochemistry
- Medical Science
Background:
- Aortic valve calcification (AVC) is a prevalent heart valve disorder, often progressing to severe aortic stenosis (AS).
- While sex-specific differences in AVC exist, with women exhibiting lower calcification burden, the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate sex-specific differences in high-density lipoprotein (HDL) cholesterol efflux capacity (CEC) in patients with severe AS.
- To explore the potential role of HDL functionality in explaining sex-based variations in AVC.
Main Methods:
- HDL particles were isolated from plasma of men and women with severe AS.
- Cholesterol efflux capacity (CEC) was measured using cultured human THP-1 macrophages and human aortic valve interstitial cells.
- ATP-Binding Cassette A1 (ABCA1)-mediated HDL-CEC and HDL particle composition (pre-β1 and α-HDL) were analyzed.
Main Results:
- Women with severe AS demonstrated significantly higher ABCA1-mediated HDL-CEC compared to men.
- Women exhibited higher levels of pre-β1 and α-HDL particles and increased lecithin-cholesterol acyltransferase (LCAT) activity.
- These findings suggest enhanced reverse cholesterol transport in women with severe AS.
Conclusions:
- Significant sex-specific differences in HDL functionality, particularly HDL-CEC, were observed in severe AS patients.
- Enhanced HDL functionality in women may contribute to their lower burden of aortic valve calcification.
- Targeting sex-related pathways in AS is crucial for advancing understanding and treatment of this condition.
Background:
Calcification of the aortic valve is a common heart valve disorder, in some cases leading to clinically impactful severe aortic stenosis (AS). Sex-specific differences in aortic valve calcification (ACV) exist, with women having a lower burden of calcification than men as measured by computed tomography; however, the pathophysiological mechanism that leads to these differences remains unclear.
Methods:
Using cultured human Tamm-Horsfall protein 1 (THP-1) macrophages and human aortic valve interstitial cells, the effects of high-density lipoprotein (HDL) particles isolated from the plasma of men and women with severe AS were studied for cholesterol efflux capacity (CEC).
Results:
HDL-CEC was assessed in 46 patients with severe AS, n = 30 men, n = 16 women. ATP-Binding Cassette A1 (ABCA1)-mediated HDL-CEC was measured from human cultured THP-1 macrophages to plasma HDL samples. Women with severe AS had more ABCA1-mediated HDL-CEC, as compared to men (8.50 ± 3.90% cpm vs. 6.80 ± 1.50% cpm, P = 0.04). HDL pre-β1 and α-particles were higher in woman than in men by spectral density, (pre-β1 HDL, 20298.29 ± 1076.15 vs. 15,661.74 ± 789.00, P = 0.002, and α-HDL, 63006.35 ± 756.81 vs. 50,447.00 ± 546.52, P = 0.03). Lecithin-cholesterol acyltransferase conversion of free cholesterol into cholesteryl esters was higher in women than men (16.44 ± 9.11%/h vs. 12.00 ± 8.07%/h, P = 0.03).
Conclusions:
Sex-specific changes in various parameters of HDL-CEC were found in patients with severe AS. Sex-based modifications in HDL functionality by HDL-CEC might account for the reduced burden of calcification in women vs. men with severe AS. Therefore, future studies should target sex-related pathways in AS to help to improve understanding and treatment of AS. Sex specifc differences in AVC and differences associated with HDL function in men and women with severe AS. When compared to men, women had higher preβ-HDL and α-HDL migrating particles, higher cholesterol efflux to HDL, and higher lecithin cholesterol acyl transferase (LCAT) activity, possibly indicating that improved reverse cholesterol transport may be protective against worsened calcification.
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