PMID- 33839697
OWN - NLM
STAT- MEDLINE
DCOM- 20210816
LR  - 20210816
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 13
IP  - 7
DP  - 2021 Apr 11
TI  - LCZ696 ameliorates lipopolysaccharide-induced endothelial injury.
PG  - 9582-9591
LID - 10.18632/aging.202692 [doi]
AB  - Lipopolysaccharide (LPS)-induced endothelial dysfunction plays an important role 
      in the pathogenesis of cardiovascular diseases. LCZ696, the dual-acting 
      angiotensin receptor blocker, and neprilysin inhibitor has been used for the 
      treatment of heart failure with reduced ejection fraction. Recent work suggests 
      that LCZ696 therapy might have an anti-inflammatory effect in cardiovascular 
      tissue. In the current study, we show that LCZ696 attenuates LPS-induced 
      oxidative stress by reducing the production of intracellular reactive oxygen 
      species (ROS) and the measurements of malonyl dialdehyde (MDA) level in human 
      umbilical vascular endothelial cells (HUVECs). LCZ696 inhibits LPS-induced 
      expressions and secretions of the pro-inflammatory cytokines, interleukin-6 
      (IL-6), interleukin-1alpha (IL-1alpha), and tumor necrosis factor beta (TNF-beta) as well as 
      the chemokines, monocyte chemotactic protein 1 (MCP-1), and chemokine (C-X-C 
      motif) ligand 1 protein (CXCL1). Additionally, we found that LCZ696 reduces 
      LPS-induced expressions of vascular cell adhesion molecule 1 (VCAM-1) and 
      P-selectin and the attachment of U937 monocytes to HUVECs. Mechanistically, 
      LCZ696 prevents LPS-induced activation of the TLR4/Myd88 pathway and nuclear 
      translocation of nuclear factor kappa-B (NF-kappaB) p65 factor. Based on these 
      findings, we conclude that LCZ696 is capable of ameliorating LPS-induced 
      endothelial dysfunction via anti-inflammatory properties.
FAU - Gao, Aihong
AU  - Gao A
AD  - Department of Cardiology, NO.215 Hospital of Shaanxi Nuclear Industry, Xianyang 
      712000, China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Cardiology, NO.215 Hospital of Shaanxi Nuclear Industry, Xianyang 
      712000, China.
FAU - Gao, Xiao
AU  - Gao X
AD  - Department of Pathology, NO.215 Hospital of Shaanxi Nuclear Industry, Xianyang 
      712000, China.
FAU - Tian, Wei
AU  - Tian W
AD  - Department of Pathology, NO.215 Hospital of Shaanxi Nuclear Industry, Xianyang 
      712000, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210411
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Aminobutyrates)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Cytokines)
RN  - 0 (Drug Combinations)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Protective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 80M03YXJ7I (Valsartan)
RN  - WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination)
SB  - IM
MH  - Aminobutyrates/*pharmacology
MH  - Biphenyl Compounds/*pharmacology
MH  - Cytokines/metabolism
MH  - Drug Combinations
MH  - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Malondialdehyde/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Protective Agents/*pharmacology
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction/drug effects
MH  - Valsartan/*pharmacology
MH  - Vascular Cell Adhesion Molecule-1/metabolism
PMC - PMC8064163
OTO - NOTNLM
OT  - LCZ696
OT  - NF-kappaB
OT  - endothelial cells
OT  - inflammation
OT  - lipopolysaccharide (LPS)
COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of 
      interests.
EDAT- 2021/04/12 06:00
MHDA- 2021/08/17 06:00
PMCR- 2021/04/15
CRDT- 2021/04/11 20:48
PHST- 2020/10/16 00:00 [received]
PHST- 2021/01/14 00:00 [accepted]
PHST- 2021/04/12 06:00 [pubmed]
PHST- 2021/08/17 06:00 [medline]
PHST- 2021/04/11 20:48 [entrez]
PHST- 2021/04/15 00:00 [pmc-release]
AID - 202692 [pii]
AID - 10.18632/aging.202692 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2021 Apr 11;13(7):9582-9591. doi: 10.18632/aging.202692. Epub 
      2021 Apr 11.