PMID- 33988313
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20220531
IS  - 2055-5822 (Electronic)
IS  - 2055-5822 (Linking)
VI  - 8
IP  - 4
DP  - 2021 Aug
TI  - Involvement of chronic inflammation via monocyte chemoattractant protein-1 in 
      uraemic cardiomyopathy: a human biopsy study.
PG  - 3156-3167
LID - 10.1002/ehf2.13423 [doi]
AB  - AIMS: Patients undergoing dialysis, even those without coronary artery disease or 
      valvular abnormalities, sometimes present with reduced heart function, which 
      resembles dilated cardiomyopathy (DCM). This condition is known as uraemic 
      cardiomyopathy (UCM). The mechanisms of UCM development are not fully understood. 
      Previous studies demonstrated that the balance between placental growth factor 
      (PlGF) and fms-like tyrosine kinase-1 (Flt-1) is correlated with renal function, 
      and PlGF/Flt-1 signalling is involved in the development of cardiovascular 
      diseases in patients with chronic kidney disease. This study was conducted to 
      evaluate the pathogenesis of UCM and clarify the differences in the mechanisms of 
      UCM and DCM by using human endomyocardial biopsy and blood samples. METHODS AND 
      RESULTS: The clinical and pathological features of 30 patients on dialysis with 
      reduced cardiac function [left ventricular ejection fraction (LVEF) </=50%] (UCM 
      group; mean age: 58.5 +/- 9.4 years and LVEF: 39.1 +/- 7.2%), 196 DCM patients (DCM 
      group; mean age: 62.7 +/- 14.0 years and LVEF: 33.5 +/- 8.8%) as controls with 
      reduced cardiac function (LVEF </= 45%), and 21 patients as controls with normal 
      cardiac function (control group; mean age: 56.2 +/- 19.3 years and LVEF: 
      67.5 +/- 6.7%) were analysed. The percentage of the interstitial fibrosis area in 
      the UCM group was greater than that in the DCM group (P = 0.045). In UCM 
      patients, the percentage of the interstitial fibrosis area was positively 
      correlated with the duration of renal replacement therapy (P < 0.001). The number 
      of infiltrated CD68-positive macrophages in the myocardium and expression of 
      monocyte chemoattractant protein-1 (MCP-1) in cardiomyocytes were significantly 
      greater in the UCM group than in the other groups (P < 0.001, respectively). 
      Furthermore, while the serum level of soluble form of Flt-1, an endogenous 
      inhibitor of PlGF, in the UCM group was lower compared with that in the DCM group 
      (P < 0.001), the serum levels of PlGF and PlGF/soluble form of Flt-1 ratio and 
      plasma level of MCP-1 in the UCM group were higher than those in the DCM group 
      (P < 0.001, respectively). CONCLUSIONS: These results suggest that activated 
      PlGF/Flt-1 signalling and subsequent macrophage-mediated chronic non-infectious 
      inflammation via MCP-1 in the myocardium are involved in the pathogenesis of UCM.
CI  - (c) 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on 
      behalf of European Society of Cardiology.
FAU - Nakano, Tomoya
AU  - Nakano T
AUID- ORCID: 0000-0001-7459-3070
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
AD  - Department of Internal Medicine, Yamato-Takada Municipal Hospital, Yamato-Takada, 
      Nara, Japan.
FAU - Onoue, Kenji
AU  - Onoue K
AUID- ORCID: 0000-0003-3233-4913
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Seno, Ayako
AU  - Seno A
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Ishihara, Satomi
AU  - Ishihara S
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Nakada, Yasuki
AU  - Nakada Y
AUID- ORCID: 0000-0003-0510-6923
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Nakagawa, Hitoshi
AU  - Nakagawa H
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Ueda, Tomoya
AU  - Ueda T
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Nishida, Taku
AU  - Nishida T
AUID- ORCID: 0000-0001-7025-0310
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Soeda, Tsunenari
AU  - Soeda T
AUID- ORCID: 0000-0001-5386-584X
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Watanabe, Makoto
AU  - Watanabe M
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Kawakami, Rika
AU  - Kawakami R
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Hatakeyama, Kinta
AU  - Hatakeyama K
AUID- ORCID: 0000-0001-7729-1836
AD  - Department of Pathology, National Cerebral and Cardiovascular Center, Suita, 
      Osaka, Japan.
AD  - Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Sakaguchi, Yasuhiro
AU  - Sakaguchi Y
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Ohbayashi, Chiho
AU  - Ohbayashi C
AUID- ORCID: 0000-0002-8046-9508
AD  - Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, 
      Japan.
FAU - Saito, Yoshihiko
AU  - Saito Y
AUID- ORCID: 0000-0001-5574-3571
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210514
PL  - England
TA  - ESC Heart Fail
JT  - ESC heart failure
JID - 101669191
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 144589-93-5 (Placenta Growth Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biopsy
MH  - *Cardiomyopathies/diagnosis/etiology
MH  - *Chemokine CCL2
MH  - Female
MH  - Humans
MH  - Inflammation
MH  - Middle Aged
MH  - Placenta Growth Factor
MH  - Stroke Volume
MH  - Ventricular Function, Left
PMC - PMC8318461
OTO - NOTNLM
OT  - Human heart tissue
OT  - Immunohistochemistry
OT  - Monocyte chemoattractant protein-1
OT  - Placental growth factor
OT  - Uraemic cardiomyopathy
COIS- None declared.
EDAT- 2021/05/15 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/05/14
CRDT- 2021/05/14 08:50
PHST- 2021/04/12 00:00 [revised]
PHST- 2020/11/24 00:00 [received]
PHST- 2021/05/02 00:00 [accepted]
PHST- 2021/05/15 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/05/14 08:50 [entrez]
PHST- 2021/05/14 00:00 [pmc-release]
AID - EHF213423 [pii]
AID - 10.1002/ehf2.13423 [doi]
PST - ppublish
SO  - ESC Heart Fail. 2021 Aug;8(4):3156-3167. doi: 10.1002/ehf2.13423. Epub 2021 May 
      14.