Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients
Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients
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DOI：
10.1038/s41598-019-51298-3
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发表时间：
2019-10-11
影响因子：
4.6
通讯作者：
Anzai, Toshihisa
中科院分区：
文献类型：
--
作者：
Shirakawa, Ryosuke;Yokota, Takashi;Anzai, Toshihisa
全身氧化应激在慢性心力衰竭（CHF）的发展中起着关键作用。我们测试了循环外周血单核细胞 (PBMC) 中线粒体活性氧 (ROS) 的产生有助于 CHF 进展的假设。共有 31 名因心力衰竭恶化而入院史的患者被纳入研究，并分为定义为纽约心脏协会 (NYHA) 功能分级 I-II 的轻度 CHF 或定义为 NYHA 功能分级 III 的中重度 CHF。与 NYHA 功能 I-II 级的 CHF 患者相比，NYHA 功能 III 级的 CHF 患者 PBMC 线粒体中的 ROS 水平显着升高，并伴有 PBMC 线粒体呼吸能力受损。在 CHF 患者中，PBMC 线粒体中 ROS 的产生与尿 8-羟基脱氧鸟苷（一种全身氧化应激标志物）呈正相关。重要的是，PBMC 中线粒体 ROS 的产生与 B 型钠尿肽（心力衰竭严重程度的生物标志物）血浆水平直接相关，与 CHF 患者的峰值摄氧量（运动能力参数）呈负相关。研究表明，晚期 CHF 患者的 PBMC 线粒体中 ROS 生成量较高，且与 CHF 患者的疾病严重程度和运动不耐受相关。
Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as NewYork Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients.