Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients

Ryosuke Shirakawa; Takashi Yokota; Takayuki Nakajima; Shingo Takada; Miwako Yamane; Takaaki Furihata; Satoshi Maekawa; Hideo Nambu; Takashi Katayama; Arata Fukushima; Akimichi Saito; Naoki Ishimori; Flemming Dela; Shintaro Kinugawa; Toshihisa Anzai

doi:10.1038/s41598-019-51298-3

Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients

Ryosuke Shirakawa, Takashi Yokota, Takayuki Nakajima, Shingo Takada, Miwako Yamane, Takaaki Furihata, Satoshi Maekawa, Hideo Nambu, Takashi Katayama, Arata Fukushima, Akimichi Saito, Naoki Ishimori, Flemming Dela, Shintaro Kinugawa, Toshihisa Anzai

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Abstract

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.

Original language	English
Article number	14709
Journal	Scientific Reports
Volume	9
Number of pages	8
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-019-51298-3
Publication status	Published - 1 Dec 2019

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OA_Mitochondrial reactive oxygenFinal published version, 1.42 MBLicence: CC BY

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Shirakawa, R., Yokota, T., Nakajima, T., Takada, S., Yamane, M., Furihata, T., Maekawa, S., Nambu, H., Katayama, T., Fukushima, A., Saito, A., Ishimori, N., Dela, F., Kinugawa, S., & Anzai, T. (2019). Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients. Scientific Reports, 9, [14709]. https://doi.org/10.1038/s41598-019-51298-3

Shirakawa, R, Yokota, T, Nakajima, T, Takada, S, Yamane, M, Furihata, T, Maekawa, S, Nambu, H, Katayama, T, Fukushima, A, Saito, A, Ishimori, N, Dela, F, Kinugawa, S & Anzai, T 2019, 'Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients', Scientific Reports, vol. 9, 14709. https://doi.org/10.1038/s41598-019-51298-3

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title = "Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients",

abstract = "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.",

author = "Ryosuke Shirakawa and Takashi Yokota and Takayuki Nakajima and Shingo Takada and Miwako Yamane and Takaaki Furihata and Satoshi Maekawa and Hideo Nambu and Takashi Katayama and Arata Fukushima and Akimichi Saito and Naoki Ishimori and Flemming Dela and Shintaro Kinugawa and Toshihisa Anzai",

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AU - Shirakawa, Ryosuke

AU - Yokota, Takashi

AU - Nakajima, Takayuki

AU - Takada, Shingo

AU - Yamane, Miwako

AU - Furihata, Takaaki

AU - Maekawa, Satoshi

AU - Nambu, Hideo

AU - Katayama, Takashi

AU - Fukushima, Arata

AU - Saito, Akimichi

AU - Ishimori, Naoki

AU - Dela, Flemming

AU - Kinugawa, Shintaro

AU - Anzai, Toshihisa

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N2 - 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.

AB - 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.

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