Solignac Justine, Dou Laetitia, Chermiti Rania, McKay Nathalie, Giaime Philippe, Pedinielli Nathalie, Benjelloun Hamza, Lano Guillaume, Mancini Julien, Burtey Stéphane, Bataille Stanislas
C2VN, Aix-Marseille University, INSERM, INRAE, 13385 Marseille, France.
Centre de Néphrologie et Transplantation Rénale, APHM, Hôpital Conception, 13005 Marseille, France.
Toxins (Basel). 2025 Mar 22;17(4):159. doi: 10.3390/toxins17040159.
Hemodialysis patients exhibit endothelial dysfunction, contributing to elevated cardiovascular risk and complications of the arteriovenous access. These patients have elevated serum levels of myostatin, a member of the transforming growth factor-β (TGFβ) superfamily, and of the uremic toxin indoxyl sulfate, both of which are pro-inflammatory towards endothelial cells. We hypothesized that myostatin and indoxyl sulfate may synergistically induce endothelial dysfunction by impairing endothelial proliferation and promoting a pro-inflammatory phenotype. We first investigated the effect of myostatin on cultured endothelial cells in the presence of indoxyl sulfate. We then examined the association between serum myostatin concentrations and the occurrence of cardiovascular and arteriovenous access complications in hemodialysis patients. In vitro, myostatin exhibited endotheliotoxic effects in the presence of a uremic concentration of indoxyl sulfate, enhanced its antiproliferative effect, and amplified MCP-1 and IL-8 chemokine upregulation. In patients, high myostatin concentrations correlated with indoxyl sulfate concentrations and were associated with an increased risk of arteriovenous access complications. These findings suggest that myostatin amplifies endothelial injury mediated by indolic uremic toxins and might contribute to AV access complications.
血液透析患者存在内皮功能障碍，这会导致心血管风险升高以及动静脉内瘘并发症。这些患者血清中肌肉生长抑制素（转化生长因子-β (TGFβ) 超家族的一员）和尿毒症毒素硫酸吲哚酚水平升高，二者均对内皮细胞具有促炎作用。我们推测，肌肉生长抑制素和硫酸吲哚酚可能通过损害内皮细胞增殖并促进促炎表型，协同诱导内皮功能障碍。我们首先研究了在存在硫酸吲哚酚的情况下，肌肉生长抑制素对培养的内皮细胞的影响。然后，我们检查了血液透析患者血清肌肉生长抑制素浓度与心血管和动静脉内瘘并发症发生之间的关联。在体外，在尿毒症浓度的硫酸吲哚酚存在下，肌肉生长抑制素表现出内皮毒性作用，增强了其抗增殖作用，并放大了单核细胞趋化蛋白-1 (MCP-1) 和白细胞介素-8 (IL-8) 趋化因子的上调。在患者中，高浓度的肌肉生长抑制素与硫酸吲哚酚浓度相关，并与动静脉内瘘并发症风险增加有关。这些发现表明，肌肉生长抑制素会放大吲哚类尿毒症毒素介导的内皮损伤，并可能导致动静脉内瘘并发症。
