Steroid biosynthesis and renal excretion in human essential hypertension: association with blood pressure and endogenous ouabain.
Steroid biosynthesis and renal excretion in human essential hypertension: association with blood pressure and endogenous ouabain.
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DOI：
10.1038/ajh.2009.3
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发表时间：
2009-04
影响因子：
3.2
通讯作者：
Manunta, Paolo
中科院分区：
文献类型：
--
作者：
Tripodi, Grazia;Citterio, Lorena;Kouznetsova, Tatiana;Lanzani, Chiara;Florio, Monica;Modica, Rossana;Messaggio, Elisabetta;Hamlyn, John M.;Zagato, Laura;Bianchi, Giuseppe;Staessen, Jan A.;Manunta, Paolo
内源性哇巴因 (EO) 与钠平衡以及心血管结构和功能的长期变化有关。 EO 的生物合成涉及胆固醇侧链裂解 (CYP11A1)、3-β-羟基类固醇脱氢酶 (HSD3B) 以及孕烯醇酮和黄体酮的连续代谢。此外，强心苷的肾脏排泄是由基底外侧膜的有机阴离子转运蛋白（SLCO4C1）和肾单位顶膜的P-糖蛋白（PGP）（由MDR1编码）介导的。记录了 729 名未经治疗的原发性高血压患者的平均 24 小时动态血压。测定醛固酮 (Aldo)、EO、尿 Na+ 和 K+ 排泄物。对总共 26 个信息丰富的 SNP 进行了单核苷酸多态性 (SNP) 和基于单倍型的关联研究。血浆EO与白天（r = 0.131，P < 0.01）和夜间舒张压（DBP）（r = 0.143，P < 0.01）显着直接相关，并且在校正混杂因素（性别、体重指数、年龄）后仍然显着相关。 EO 水平和日间 DBP 的基因型分析对 CYP11A1 rs11638442 和 MDR1 rs1045642 (T/C Ile1145) 给出了显着结果，其中次要等位基因跟踪较高的 EO 水平 (T/T 210.3 (147–272) vs. C/C 270.7 (193–366) pmol/l，P < 0.001）。发现 HSD3B1 多态性和/或单倍型与血压（收缩压 (SBP) 140.3 (11.7) 与 143.8 (11.2) mm Hg，P < 0.01）和血浆 Aldo (P < 0.05) 之间存在关联。基于单倍型的分析支持 SNP 分析的数据。在原发性高血压患者中，胆固醇侧链裂解和 MDR1 位点与循环 EO 和 DBP 相关，很可能分别影响 EO 合成和跨膜转运。相比之下，HSD3B1 的变异可能通过 Aldo 与 SBP 相关。
Endogenous ouabain (EO) has been linked with long-term changes in sodium balance and cardiovascular structure and function. The biosynthesis of EO involves, cholesterol side-chain cleavage (CYP11A1), 3-β-hydroxysteroid dehydrogenase (HSD3B) with sequential metabolism of pregnenolone and progesterone. Furthermore, the renal excretion of cardiac glycosides is mediated by the organic anion transporter (SLCO4C1) at the basolateral membrane and the P-glycoprotein (PGP) (encoded by MDR1) at the apical membrane of the nephron. Average 24-h ambulatory blood pressures were recorded in 729 untreated essential hypertensives. Aldosterone (Aldo), EO, urinary Na+, and K+ excretions were determined. Single-nucleotide polymorphism (SNP) and haplotype-based association study was performed with a total of 26 informative SNPs. Plasma EO was significantly directly related to both day (r = 0.131, P < 0.01) and nighttime diastolic blood pressure (DBP) (r = 0.143, P < 0.01), and remained significantly related after correction for confounders (sex, body mass index, age). Genotype analysis for EO levels and daytime DBP gave significant results for CYP11A1 rs11638442 and MDR1 rs1045642 (T/C Ile1145) in which the minor allele tracked with higher EO levels (T/T 210.3 (147–272) vs. C/C 270.7 (193–366) pmol/l, P < 0.001). Association was found between HSD3B1 polymorphisms and/or haplotypes with blood pressure (systolic blood pressure (SBP) 140.3 (11.7) vs. 143.8 (11.2) mm Hg, P < 0.01) and plasma Aldo (P < 0.05). Haplotype-based analyses support the data of SNP analysis. Among patients with essential hypertension, cholesterol side-chain cleavage and MDR1 loci are related to circulating EO and DBP, most likely by influencing EO synthesis and transmembrane transport, respectively. In contrast, variants in HSD3B1 are related with SBP probably via Aldo.
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影响因子：
6.7
作者：
Johne, A;Köpke, K;Roots, I
通讯作者：
Roots, I
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
DOI：
10.1016/0006-291x(92)91593-f
发表时间：
1992-11-30
影响因子：
3.1
作者：
DELANNOY, IAM;SILVERMAN, M
通讯作者：
SILVERMAN, M
DOI：
10.1073/pnas.0304987101
发表时间：
2004-03-09
影响因子：
11.1
作者：
Mikkaichi, T;Suzuki, T;Abe, T
通讯作者：
Abe, T
影响因子：
3.1
作者：
Ferrandi, M;Manunta, P;Bianchi, G
通讯作者：
Bianchi, G