PMID- 31605012
OWN - NLM
STAT- MEDLINE
DCOM- 20201106
LR  - 20210110
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Oct 11
TI  - Mitochondrial reactive oxygen species generation in blood cells is associated 
      with disease severity and exercise intolerance in heart failure patients.
PG  - 14709
LID - 10.1038/s41598-019-51298-3 [doi]
LID - 14709
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 New York 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.
FAU - Shirakawa, Ryosuke
AU  - Shirakawa R
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Yokota, Takashi
AU  - Yokota T
AUID- ORCID: 0000-0001-5470-6648
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan. t-yokota@med.hokudai.ac.jp.
FAU - Nakajima, Takayuki
AU  - Nakajima T
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Takada, Shingo
AU  - Takada S
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Yamane, Miwako
AU  - Yamane M
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Furihata, Takaaki
AU  - Furihata T
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Maekawa, Satoshi
AU  - Maekawa S
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Nambu, Hideo
AU  - Nambu H
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Katayama, Takashi
AU  - Katayama T
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Fukushima, Arata
AU  - Fukushima A
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Saito, Akimichi
AU  - Saito A
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Ishimori, Naoki
AU  - Ishimori N
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Dela, Flemming
AU  - Dela F
AD  - Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of 
      Copenhagen, Copenhagen, Denmark.
AD  - Department of Geriatrics, Bispebjerg-Frederiksberg University Hospital, 
      Copenhagen, Denmark.
FAU - Kinugawa, Shintaro
AU  - Kinugawa S
AUID- ORCID: 0000-0003-2559-0054
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Anzai, Toshihisa
AU  - Anzai T
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191011
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers)
RN  - 0 (Reactive Oxygen Species)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine/urine
MH  - Aged
MH  - Biomarkers/blood
MH  - Chronic Disease
MH  - Exercise Test
MH  - *Exercise Tolerance
MH  - Female
MH  - Heart Failure/*physiopathology
MH  - Humans
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Mitochondria/*metabolism
MH  - Natriuretic Peptide, Brain/blood
MH  - Oxygen Consumption
MH  - Reactive Oxygen Species/*metabolism
MH  - *Severity of Illness Index
PMC - PMC6789126
COIS- The authors declare no competing interests.
EDAT- 2019/10/13 06:00
MHDA- 2020/11/11 06:00
PMCR- 2019/10/11
CRDT- 2019/10/13 06:00
PHST- 2019/05/30 00:00 [received]
PHST- 2019/09/29 00:00 [accepted]
PHST- 2019/10/13 06:00 [entrez]
PHST- 2019/10/13 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2019/10/11 00:00 [pmc-release]
AID - 10.1038/s41598-019-51298-3 [pii]
AID - 51298 [pii]
AID - 10.1038/s41598-019-51298-3 [doi]
PST - epublish
SO  - Sci Rep. 2019 Oct 11;9(1):14709. doi: 10.1038/s41598-019-51298-3.