Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, 1001 Boulevard Decarie, Montreal, Québec, H3A 1A1, Canada.
Department of Food and Drug, University of Parma, Parma, Italy.
Lipids Health Dis. 2022 May 28;21(1):48. doi: 10.1186/s12944-022-01653-7.
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.
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).
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).
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.
主动脉瓣钙化是一种常见的心脏瓣膜疾病，在某些情况下可导致临床上有影响的严重主动脉瓣狭窄（AS）。主动脉瓣钙化（ACV）存在性别差异，女性的钙化负担低于男性，这可以通过计算机断层扫描来衡量；然而，导致这些差异的病理生理机制仍不清楚。
使用培养的人 Tamm-Horsfall 蛋白 1（THP-1）巨噬细胞和人主动脉瓣间质细胞，研究了从严重 AS 男性和女性血浆中分离的高密度脂蛋白（HDL）颗粒对胆固醇流出能力（CEC）的影响。
对 46 名严重 AS 患者进行了 HDL-CEC 评估，n=30 名男性，n=16 名女性。从人培养的 THP-1 巨噬细胞到血浆 HDL 样本中测量了 ATP 结合盒转运体 A1（ABCA1）介导的 HDL-CEC。与男性相比，患有严重 AS 的女性具有更高的 ABCA1 介导的 HDL-CEC（8.50±3.90% cpm 比 6.80±1.50% cpm，P=0.04）。女性的 HDL 前β1 和 α-颗粒的谱密度高于男性（前β1 HDL，20298.29±1076.15 比 15661.74±789.00，P=0.002，和α-HDL，63006.35±756.81 比 50447.00±546.52，P=0.03）。女性的卵磷脂胆固醇酰基转移酶将游离胆固醇转化为胆固醇酯的转化率高于男性（16.44±9.11%/h 比 12.00±8.07%/h，P=0.03）。
在严重 AS 患者中发现了各种 HDL-CEC 参数的性别特异性变化。严重 AS 患者中 HDL 功能的基于性别的改变可能解释了女性与男性相比钙化负担减轻的原因。因此，未来的研究应针对 AS 的性别相关途径，以帮助改善对 AS 的理解和治疗。AS 中的性别特异性差异和严重 AS 男性和女性中与 HDL 功能相关的差异。与男性相比，女性具有更高的前β-HDL 和α-HDL 迁移颗粒，更高的胆固醇流出到 HDL，以及更高的卵磷脂胆固醇酰基转移酶（LCAT）活性，这可能表明改善胆固醇逆向转运可能对改善钙化具有保护作用。
