Potential associations of circulating growth differentiation factor-15 with sex hormones in male patients with coronary artery disease
Potential associations of circulating growth differentiation factor-15 with sex hormones in male patients with coronary artery disease
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男性冠心病患者循环生长分化因子 15 与性激素的潜在关联
DOI：
10.1016/j.biopha.2019.108792
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发表时间：
2019-06-01
影响因子：
7.5
通讯作者：
Li, Yan
中科院分区：
文献类型：
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作者：
Liu, Huan;Dai, Wen;Li, Yan
本研究旨在探讨应激诱导因子生长分化因子15（GDF-15）与男性冠心病患者性激素水平的关系。在这项研究中，我们招募了253名男性CAD患者和205名男性对照。根据GDF-15三分位数将患者分为三组。测量GDF-15、睾酮、雌二醇和其他生化变量的血清水平。与对照组相比，CAD患者血清GDF-15水平显著升高，血清睾酮和睾酮/雌二醇比值（T/ E2比值）显著降低。GDF-15水平高的患者睾酮水平较低（203.97，95% CI 154.67-328.30 vs. 303.98，95% CI 246.93-345.66; P = 0.001）和T/E2比值（8.82，95% CI 5.77-11.41对比11.07，95% CI 7.91-14.32; P = 0.013）。相关分析显示，血清GDF-15水平与睾酮水平（r =-0.339）、T/E2比值（r =-0.365）呈负相关（均P < 0.001）。在多变量回归分析中，GDF-15与T/E2比值之间的相关性得以维持（B =-0.442，95% CI -99.568至-6.991，P = 0.015）。此外，体外研究显示睾酮和雌二醇对GDF-15分泌的协同作用，并证明睾酮与雌二醇的结合通过雄激素受体/雌激素受体介导的途径降低GDF-15分泌。总之，这些结果表明，在低的和不平衡的性激素水平的存在下，GDF-15的上调可能有助于CAD。因此，恢复睾酮和雌二醇的平衡可以抑制GDF-15的作用，并作为治疗CAD的有希望的治疗策略。
This study aimed to explore the association between growth differentiation factor-15 (GDF-15), a stress-induced factor, and sex hormones in male patients with coronary artery disease (CAD). In this study, we recruited 253 male patients with CAD and 205 male controls. Patients were divided into three groups in accordance with GDF-15 tertiles. Serum levels of GDF-15, testosterone, estradiol and other biochemical variables were measured. Serum levels of GDF-15 were significantly increased and serum testosterone and testosterone/estradiol ratio (T/ E2 ratio) were significantly decreased in CAD patients compared with controls. Patients with high GDF-15 levels had lower testosterone (203.97, 95% CI 154.67-328.30 vs. 303.98, 95% CI 246.93-345.66; P = 0.001) and T/E2 ratio (8.82, 95% CI 5.77-11.41 vs. 11.07, 95% CI 7.91-14.32; P = 0.013). Correlation analyses showed that serum GDF-15 levels inversely correlated with testosterone levels (r = - 0.339) and T/E2 ratio (r = - 0.365) (both P < 0.001). In multivariate regression analyses, the association between GDF-15 and T/E2 ratio was maintained (B =-0.442, 95% CI -99.568 to -6.991, P = 0.015). Furthermore, in vitro studies showed a synergistic effect of testosterone and estradiol on GDF-15 secretion, and demonstrated that testosterone association with estradiol decreased GDF-15 secretion through androgen receptor/estrogen receptor-mediated pathways. Together, these results suggest that upregulation of GDF-15 in the presence of low and imbalanced sex hormone levels may contribute to CAD. Thus, restoring the balance of testosterone and estradiol may inhibit the effects of GDF-15 and serve as a promising therapeutic strategy for the treatment of CAD.