Background:Cardiac sialylation is involved in a variety of physiological processes in the heart. Altered sialylation has been implicated in heart failure (HF) mice. However, its role in patients with HF is unclear, and the potential effect of modulation of cardiac sialylation is worth exploring.Methods:We first assessed the association between plasma N-acetylneuraminic acid levels and the incidence of adverse cardiovascular events in patients with HF over a median follow-up period of 2 years. Next, immunoblot analysis and lectin histochemistry were performed in cardiac tissue to determine the expression levels of neuraminidases and the extent of cardiac desialylation. Finally, the therapeutic impact of a neuraminidase inhibitor was evaluated in animal models of HF.Results:Among 1699 patients with HF, 464 (27%) died of cardiovascular-related deaths or underwent heart transplantation. We found that the elevated plasma N-acetylneuraminic acid level was independently associated with a higher risk of incident cardiovascular death and heart transplantation (third tertile adjusted hazard ratio, 2.11 [95% CI, 1.67–2.66], P<0.001). In addition, in cardiac tissues from patients with HF, neuraminidase expression was upregulated, accompanied by desialylation. Treatment with oseltamivir, a neuraminidase inhibitor, in HF mice infused with isoproterenol and angiotensin II significantly inhibited desialylation and ameliorated cardiac dysfunction.Conclusions:This study uncovered a significant association between elevated plasma N-acetylneuraminic acid level and an increased risk of a poor clinical outcome in patients with HF. Our data support the notion that desialylation represents an important contributor to the progression of HF, and neuraminidase inhibition may be a potential therapeutic strategy for HF.

中文翻译：

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血浆 N-乙酰神经氨酸水平升高对心力衰竭患者的预后价值

背景：心脏唾液酸化参与心脏的多种生理过程。改变的唾液酸化与心力衰竭 (HF) 小鼠有关。然而，其在 HF 患者中的作用尚不清楚，调节心脏唾液酸化的潜在作用值得探索。中位随访期为 2 年。接下来，在心脏组织中进行免疫印迹分析和凝集素组织化学，以确定神经氨酸酶的表达水平和心脏去唾液酸化的程度。最后，在 HF 动物模型中评估了神经氨酸酶抑制剂的治疗效果。 结果：在 1699 名 HF 患者中，464 人（27%）死于心血管相关死亡或接受心脏移植。我们发现血浆 N-乙酰神经氨酸水平升高与更高的心血管死亡和心脏移植风险独立相关（调整后的三分位数风险比，2.11 [95% CI，1.67–2.66]，P <0.001）。此外，在 HF 患者的心脏组织中，神经氨酸酶表达上调，并伴有去唾液酸化。用神经氨酸酶抑制剂奥司他韦治疗 HF 小鼠，注射异丙肾上腺素和血管紧张素 II 可显着抑制去唾液酸化并改善心脏功能障碍。在 HF 患者中。我们的数据支持去唾液酸化是导致 HF 进展的重要因素的观点，神经氨酸酶抑制可能是 HF 的潜在治疗策略。