白细胞介素 8 和基质金属蛋白酶 9 水平升高与使用合成代谢雄激素类固醇患者的心肌病理学有关。

Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of anabolic-androgenic steroids.

机构信息

Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway.

Anabolic Androgenic Steroid Research Group, Section of Clinical Addiction Research, Division of Mental Health and Addiction, Oslo University Hospital, Sognsvannsveien 21, 0372 Oslo, Norway.

出版信息

Eur J Prev Cardiol. 2024 Sep 6;31(12):1469-1476. doi: 10.1093/eurjpc/zwae126.

DOI:10.1093/eurjpc/zwae126

PMID:38573232

Abstract

AIMS

In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodelling and their association with hormones and echocardiographic myocardial pathology in weightlifters.

METHODS AND RESULTS

In a cross-sectional study, 93 weightlifting AAS users, of whom 62 were current and 31 were past users, with at least 1-year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use), were compared with 54 non-using weightlifting controls (WLCs) using clinical interview, blood pressure measurements, and echocardiography. Serum levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF), interferon (IFN)-γ, growth differentiation factor (GDF)-15, and matrix metalloproteinase (MMP)-9, sex hormones, and lipids were analysed. It was found that serum levels of IL-8, GDF-15, and MMP-9 were significantly increased in current AAS users compared with former users and WLCs. Matrix metalloproteinase 9, but not IL-8, correlated consistently with sex hormone levels, and sex hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current vs. former AAS users and significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP-9 also correlated with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users.

CONCLUSION

Long-term AAS is associated with increased levels of markers of inflammation and ECM remodelling, which seems to have a hormone-dependent (MMP-9) and a hormone-independent (IL-8) association with markers of myocardial dysfunction.

摘要

目的

在本研究中，我们旨在探究当前和既往长期使用合成代谢雄激素类固醇（AAS）对系统性炎症标志物和细胞外基质（ECM）重塑介质的调节作用，以及它们与激素和举重运动员心肌病理学的关系。

方法和结果

在一项横断面研究中，我们比较了 93 名使用 AAS 的举重运动员（其中 62 名为当前使用者，31 名为既往使用者，至少有 1 年累积 AAS 使用史（平均 11±7 年））与 54 名未使用 AAS 的举重对照者（WLCs）的临床访谈、血压测量和超声心动图结果。分析了血清白细胞介素（IL）-6、IL-8、肿瘤坏死因子（TNF）、干扰素（IFN）-γ、生长分化因子（GDF）-15 和基质金属蛋白酶（MMP）-9、性激素和血脂水平。结果发现，与既往使用者和 WLCs 相比，当前使用者的血清 IL-8、GDF-15 和 MMP-9 水平显著升高。MMP-9 而非 IL-8 与当前使用者的性激素水平始终相关，性激素水平与平均壁厚度始终相关。此外，当前使用者的 HDL 胆固醇水平显著低于既往使用者，且与当前使用者的 MMP-9 呈显著负相关。此外，在当前使用者中，MMP-9 和 IL-8 与心肌应变标志物相关，而 MMP-9 也与心脏质量指数相关，而在既往使用者中则未观察到这种相关性。中介分析表明，MMP-9 可以部分解释当前使用者中激素诱导的心肌损伤标志物的改变。