PMID- 34418354
OWN - NLM
STAT- MEDLINE
DCOM- 20211115
LR  - 20211115
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 192
DP  - 2021 Oct
TI  - The C-terminal cleavage of angiotensin II and III is mediated by prolyl 
      carboxypeptidase in human umbilical vein and aortic endothelial cells.
PG  - 114738
LID - S0006-2952(21)00354-3 [pii]
LID - 10.1016/j.bcp.2021.114738 [doi]
AB  - The renin-angiotensin system, with the octapeptide angiotensin II as key player, 
      is important in the renal, cardiac and vascular physiology. Prolyl 
      carboxypeptidase (PRCP), prolyl endopeptidase (PREP) and angiotensin converting 
      enzyme 2 (ACE2) are reported to be involved in the conversion of angiotensin II 
      to angiotensin (1-7). Previous investigations showed that the processing of 
      angiotensin II is cell- and species-specific and little is known about its 
      conversion in human endothelial cells. Therefore, we aimed to investigate the 
      C-terminal processing of angiotensin II and III in comparison to the processing 
      of des-Arg(9)-bradykinin in human endothelial cells. To this end, human umbilical 
      vein and aortic endothelial cells (HUVEC and HAoEC) were incubated with the 
      peptides for different time periods. Mass spectrometry analysis was performed on 
      the supernatants to check for cleavage products. Contribution of PRCP, ACE2 and 
      PREP to the peptide cleavage was evaluated by use of the selective inhibitors 
      compound 8o, DX600 and KYP-2047. The use of these selective inhibitors revealed 
      that the C-terminal cleavage of angiotensin II and III was PRCP-dependent in 
      HUVEC and HAoEC. In contrast, the C-terminal cleavage of des-Arg(9)-bradykinin 
      was PRCP-dependent in HUVEC and PRCP- and ACE2-dependent in HAoEC. With this 
      study, we contribute to a better understanding of the processing of peptides 
      involved in the alternative renin-angiotensin system. We conclude that PRCP is 
      the main enzyme for the C-terminal processing of angiotensin peptides in human 
      umbilical vein and aortic endothelial cells. For the first time the contribution 
      of PRCP was investigated by use of a selective PRCP-inhibitor.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - De Hert, Emilie
AU  - De Hert E
AD  - Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium.
FAU - Bracke, An
AU  - Bracke A
AD  - Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium.
FAU - Lambeir, Anne-Marie
AU  - Lambeir AM
AD  - Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium.
FAU - Van der Veken, Pieter
AU  - Van der Veken P
AD  - Laboratory of Medicinal Chemistry, University of Antwerp, Antwerp, Belgium.
FAU - De Meester, Ingrid
AU  - De Meester I
AD  - Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium. 
      Electronic address: ingrid.demeester@uantwerpen.be.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210819
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (DX600 peptide)
RN  - 0 (Peptides)
RN  - 11128-99-7 (Angiotensin II)
RN  - 12687-51-3 (Angiotensin III)
RN  - EC 3.4.- (Carboxypeptidases)
RN  - EC 3.4.16.2 (lysosomal Pro-X carboxypeptidase)
SB  - IM
MH  - Angiotensin II/*metabolism
MH  - Angiotensin III/antagonists & inhibitors/*metabolism
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacology
MH  - Aorta/cytology/drug effects/*metabolism
MH  - Carboxypeptidases/antagonists & inhibitors/*metabolism
MH  - Cells, Cultured
MH  - Human Umbilical Vein Endothelial Cells/drug effects/*metabolism
MH  - Humans
MH  - Peptides/pharmacology
OTO - NOTNLM
OT  - Angiotensin converting enzyme 2
OT  - Human endothelial cells
OT  - Prolyl carboxypeptidase
OT  - Prolyl endopeptidase
OT  - Renin-angiotensin system
OT  - des-Arg(9)-bradykinin
EDAT- 2021/08/22 06:00
MHDA- 2021/11/16 06:00
CRDT- 2021/08/21 20:11
PHST- 2021/06/11 00:00 [received]
PHST- 2021/08/14 00:00 [revised]
PHST- 2021/08/16 00:00 [accepted]
PHST- 2021/08/22 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2021/08/21 20:11 [entrez]
AID - S0006-2952(21)00354-3 [pii]
AID - 10.1016/j.bcp.2021.114738 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2021 Oct;192:114738. doi: 10.1016/j.bcp.2021.114738. Epub 2021 
      Aug 19.