Measures of high-density lipoprotein function in men and women with severe aortic stenosis

Abstract 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 measure...

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Main Authors: Anouar Hafiane, Elda Favari, Anna E. Bortnick
Format: Article
Language:English
Published: BMC 2022-05-01
Series:Lipids in Health and Disease
Subjects:
Online Access:https://doi.org/10.1186/s12944-022-01653-7
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author Anouar Hafiane
Elda Favari
Anna E. Bortnick
author_facet Anouar Hafiane
Elda Favari
Anna E. Bortnick
author_sort Anouar Hafiane
collection DOAJ
description Abstract 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. Graphical abstract 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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spelling doaj.art-0d976988551443b7b28c8236bd70d7772022-12-22T03:23:55ZengBMCLipids in Health and Disease1476-511X2022-05-0121111010.1186/s12944-022-01653-7Measures of high-density lipoprotein function in men and women with severe aortic stenosisAnouar Hafiane0Elda Favari1Anna E. Bortnick2Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health CentreDepartment of Food and Drug, University of ParmaDepartment of Medicine, Division of CardiologyAbstract 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. Graphical abstract 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.https://doi.org/10.1186/s12944-022-01653-7High-density lipoproteinCholesterol efflux capacityValveAortic stenosisCalcification
spellingShingle Anouar Hafiane
Elda Favari
Anna E. Bortnick
Measures of high-density lipoprotein function in men and women with severe aortic stenosis
Lipids in Health and Disease
High-density lipoprotein
Cholesterol efflux capacity
Valve
Aortic stenosis
Calcification
title Measures of high-density lipoprotein function in men and women with severe aortic stenosis
title_full Measures of high-density lipoprotein function in men and women with severe aortic stenosis
title_fullStr Measures of high-density lipoprotein function in men and women with severe aortic stenosis
title_full_unstemmed Measures of high-density lipoprotein function in men and women with severe aortic stenosis
title_short Measures of high-density lipoprotein function in men and women with severe aortic stenosis
title_sort measures of high density lipoprotein function in men and women with severe aortic stenosis
topic High-density lipoprotein
Cholesterol efflux capacity
Valve
Aortic stenosis
Calcification
url https://doi.org/10.1186/s12944-022-01653-7
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