PMID- 34516679
OWN - NLM
STAT- MEDLINE
DCOM- 20211027
LR  - 20211027
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 35
IP  - 10
DP  - 2021 Oct
TI  - Apela inhibits systemic and renal inflammatory reactions in mice with type I 
      cardiorenal syndrome.
PG  - e21907
LID - 10.1096/fj.202101030R [doi]
AB  - This study investigated the effect of apela on renal function and 
      anti-inflammatory effect on whole body and kidney tissue in mice with type I 
      cardiorenal syndrome (CRS). The murine type I CRS model was established and apela 
      was subcutaneously infused for two weeks. Cardiac and renal functions were 
      evaluated by echocardiography and blood biochemistry, respectively. The systemic 
      and renal inflammatory responses were examined with molecular biological and 
      histological methods. Human renal glomerular endothelial cells (RGECs) were used 
      to evaluate the adhesion effect of monocytes in vitro. Compared to mice from the 
      control group (CRS + vehicle), the plasma levels of N-terminal pro-brain 
      natriuretic peptide, blood urea nitrogen and creatinine were significantly 
      decreased, while the mean left ventricular ejection fraction was increased in 
      apela-treated CRS mice at the 4th week. The expression of monocyte 
      chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in the 
      circulation and kidney was decreased in apela-treated mice compared with control 
      mice, and apela improved cardio-renal pathology in mice with type I CRS. 
      Additionally, Apela significantly suppressed the expression of MCP-1, TNF-alpha, 
      intercellular adhesion molecule-1 and vascular intercellular adhesion molecule-1 
      in RGECs induced by angiotensin II (Ang II), and inhibited the promoting effect 
      of Ang II on the adhesion of THP-1 cells to RGECs. Western blot results showed 
      that the expression of phosphorylated nuclear factor kappa B (phospho-NFkappaB) in 
      CRS mice was increased, but the expression of phospho-NFkappaB was down-regulated 
      after apela treatment. Furthermore, apela significantly inhibited the Ang 
      II-mediated increase in phospho-NFkappaB expression in RGECs in vitro, but the 
      administration of an apelin peptide jejunum receptor (APJ) inhibitor blocked the 
      inhibitory effect of apela. This study revealed that apela improves cardiorenal 
      function and reduces systemic and renal inflammatory response in type I CRS mice 
      and the apela/APJ system may alleviate renal inflammatory responses by inhibiting 
      the NFkappaB signalling pathway.
CI  - (c) 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on 
      behalf of Federation of American Societies for Experimental Biology.
FAU - Jin, Liangli
AU  - Jin L
AD  - Department of Cardiovascular Medicine, Affiliated Nanjing Brain Hospital, Nanjing 
      Medical University, Nanjing, China.
FAU - Li, Quanyi
AU  - Li Q
AD  - Department of Cardiovascular Medicine, Affiliated Nanjing Brain Hospital, Nanjing 
      Medical University, Nanjing, China.
FAU - Li, Jing
AU  - Li J
AD  - Department of Cardiovascular Medicine, Affiliated Nanjing Brain Hospital, Nanjing 
      Medical University, Nanjing, China.
FAU - Pan, Yang
AU  - Pan Y
AD  - Department of Cardiovascular Medicine, Affiliated Nanjing Brain Hospital, Nanjing 
      Medical University, Nanjing, China.
FAU - Zou, Jue
AU  - Zou J
AD  - Department of Pathology, Affiliated Nanjing Brain Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Wu, Xiaoyuan
AU  - Wu X
AD  - Department of Central Laboratory, Affiliated Nanjing Brain Hospital, Nanjing 
      Medical University, Nanjing, China.
FAU - Wang, Zhi
AU  - Wang Z
AUID- ORCID: 0000-0003-2408-9882
AD  - Department of Cardiovascular Medicine, Affiliated Nanjing Brain Hospital, Nanjing 
      Medical University, Nanjing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Apela protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptide Hormones)
SB  - IM
MH  - Animals
MH  - Cardio-Renal Syndrome/*complications/*pathology
MH  - Heart/physiology/physiopathology
MH  - Humans
MH  - Inflammation/*complications/pathology/*prevention & control
MH  - *Kidney/pathology/physiology/physiopathology
MH  - Kidney Glomerulus/cytology
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Peptide Hormones/*metabolism
MH  - Phosphorylation
MH  - THP-1 Cells
OTO - NOTNLM
OT  - apela
OT  - apelin peptide jejunum receptor
OT  - inflammation
OT  - nuclear factor kappa B
OT  - type I cardiorenal syndrome
EDAT- 2021/09/14 06:00
MHDA- 2021/10/28 06:00
CRDT- 2021/09/13 17:33
PHST- 2021/08/19 00:00 [revised]
PHST- 2021/06/22 00:00 [received]
PHST- 2021/08/24 00:00 [accepted]
PHST- 2021/09/13 17:33 [entrez]
PHST- 2021/09/14 06:00 [pubmed]
PHST- 2021/10/28 06:00 [medline]
AID - 10.1096/fj.202101030R [doi]
PST - ppublish
SO  - FASEB J. 2021 Oct;35(10):e21907. doi: 10.1096/fj.202101030R.