Atrial Natriuretic Peptide Inhibited ABCA1/G1-dependent Cholesterol Efflux Related to Low HDL-C in Hypertensive Pregnant Patients.
Atrial Natriuretic Peptide Inhibited ABCA1/G1-dependent Cholesterol Efflux Related to Low HDL-C in Hypertensive Pregnant Patients.
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心房钠尿肽抑制与高血压孕妇低 HDL-C 相关的 ABCA1/G1 依赖性胆固醇流出
DOI：
10.3389/fphar.2021.715302
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发表时间：
2021
影响因子：
5.6
通讯作者：
Song W
中科院分区：
文献类型：
--
作者：
Dong Y;Lin Y;Liu W;Zhang W;Jiang Y;Song W
目的：据报道，心房钠尿肽（ANP）通过刺激脂肪细胞褐变、脂解和脂质氧化以及影响脂肪因子的分泌来调节脂质代谢。在我们先前的研究中，我们发现妊娠期高血压疾病（HDP）患者的血浆ANP浓度相较于血压正常的妊娠患者显著升高。因此，本研究的目的是调查HDP患者的脂质谱，并确定ANP对THP - 1巨噬细胞中胆固醇流出的影响。
方法：共招募了265例HDP患者和178例血压正常的女性作为对照组。收集临床人口统计学特征和实验室检查资料。比较两组的血浆总甘油三酯（TGs）、总胆固醇（TC）、低密度胆固醇（LDL - C）和高密度胆固醇（HDL - C）。将THP - 1单核细胞与不同浓度的ANP一起培养。评估ATP结合盒转运体A1（ABCA1）和ATP结合盒转运体G1（ABCG1）的mRNA和蛋白质。通过绿色荧光标记的NBD胆固醇分别测量ABCA1和ABCG1介导的胆固醇向载脂蛋白A - Ⅰ（apoA - Ⅰ）和高密度脂蛋白（HDL）的流出。研究钠尿肽受体A（NPR - A）小干扰RNA以及过氧化物酶体增殖物激活受体 - γ（PPAR - γ）和肝X受体α（LXRα）的特异性激动剂以探究所涉及的机制。
结果：与对照组相比，HDP组的血浆TG、TC、LDL - C和LDL - C/HDL - C显著升高，HDL - C显著降低（所有p < 0.001）。ANP以剂量依赖的方式在mRNA和蛋白质水平抑制ABCA1和ABCG1的表达。ABCA1和ABCG1介导的胆固醇向apoA - I和HDL流出的功能显著降低。NPR - A小干扰RNA进一步证实ANP与其受体结合通过PPAR - γ/LXRα途径抑制ABCA1/G1表达。
结论：在THP - 1巨噬细胞中，当ANP与NPR - A结合时，通过PPAR - γ/LXRα途径刺激抑制ABCA1/G1。ANP的刺激也损害ABCA1/G1介导的胆固醇流出。这可能为HDP患者中HDL - C水平降低提供一种新的解释。
Objective: It has been reported that atrial natriuretic peptide (ANP) regulates lipid metabolism by stimulating adipocyte browning, lipolysis, and lipid oxidation, and by impacting the secretion of adipokines. In our previous study, we found that the plasma ANP concentration of hypertensive disorders of pregnancy (HDP) was significantly increased in comparison to that of normotensive pregnancy patients. Thus, this study’s objective was to investigate the lipid profile in patients with HDP and determine the effects of ANP on the cholesterol efflux in THP-1 macrophages. Methods: A total of 265 HDP patients and 178 normotensive women as the control group were recruited. Clinical demographic characteristics and laboratory profile data were collected. Plasma total triglycerides (TGs), total cholesterol (TC), low-density cholesterol (LDL-C), and high-density cholesterol (HDL-C) were compared between the two groups. THP-1 monocytes were incubated with different concentrations of ANP. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) mRNA and protein were evaluated. ABCA1- and ABCG1-mediated cholesterol efflux to apolipoprotein A-Ⅰ (apoA-Ⅰ) and HDL, respectively, were measured by green fluorescent labeled NBD cholesterol. Natriuretic peptide receptor A (NPR-A) siRNA and specific agonists of the peroxisome proliferator–activated receptor-γ (PPAR-γ) and liver X receptor α (LXRα) were studied to investigate the mechanism involved. Results: Plasma TG, TC, LDL-C, and LDL-C/HDL-C were significantly increased, and HDL-C was significantly decreased in the HDP group in comparison to the control (all p < 0.001). ANP inhibited the expression of ABCA1 and ABCG1 at both the mRNA and protein levels in a dose-dependent manner. The functions of ABCA1- and ABCG1-mediated cholesterol efflux to apoA-I and HDL were significantly decreased. NPR-A siRNA further confirmed that ANP binding to its receptor inhibited ABCA1/G1 expression through the PPAR-γ/LXRα pathway. Conclusions: ABCA1/G1 was inhibited by the stimulation of ANP when combined with NPR-A through the PPAR-γ/LXRα pathway in THP-1 macrophages. The ABCA1/G1-mediated cholesterol efflux was also impaired by the stimulation of ANP. This may provide a new explanation for the decreased level of HDL-C in HDP patients.
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影响因子：
4.6
作者：
Kimura H;Nagoshi T;Yoshii A;Kashiwagi Y;Tanaka Y;Ito K;Yoshino T;Tanaka TD;Yoshimura M
通讯作者：
Yoshimura M
Corin、N端心房钠尿肽前体与妊娠期高血压疾病新生儿不良预后的相关性
DOI：
10.1016/j.preghy.2020.11.007
发表时间：
2021-03-01
影响因子：
2.2
作者：
Lin, Yi;Dong, Yu-bing;Song, Wei
通讯作者：
Song, Wei
DOI：
10.1073/pnas.94.26.14730
发表时间：
1997-12-23
影响因子：
11.1
作者：
Oliver, PM;Fox, JE;Maeda, N
通讯作者：
Maeda, N
影响因子：
5.8
作者：
Birkenfeld, AL;Boschmann, M;Jordan, J
通讯作者：
Jordan, J
影响因子：
15.9
作者：
Li, AC;Brown, KK;Glass, CK
通讯作者：
Glass, CK