Related Experiment Video
Updated: Nov 9, 2025
Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
LCZ696 ameliorates lipopolysaccharide-induced endothelial injury
Aihong Gao1, Yu Wang1, Xiao Gao2
1Department of Cardiology, NO.215 Hospital of Shaanxi Nuclear Industry, Xianyang 712000, China.
Insights
LCZ696 reduces inflammation and oxidative stress in endothelial cells damaged by lipopolysaccharide (LPS). This dual-acting drug, LCZ696, ameliorates endothelial dysfunction by inhibiting key inflammatory pathways.
Area of Science:
- Cardiovascular Biology
- Pharmacology
- Immunology
Background:
- Endothelial dysfunction induced by lipopolysaccharide (LPS) is a key factor in cardiovascular disease development.
- LCZ696, a combined angiotensin receptor blocker and neprilysin inhibitor, is used for heart failure but may possess anti-inflammatory properties.
Purpose of the Study:
- To investigate the anti-inflammatory and protective effects of LCZ696 on LPS-induced endothelial dysfunction.
- To elucidate the underlying molecular mechanisms of LCZ696's action in human umbilical vascular endothelial cells (HUVECs).
Main Methods:
- Treatment of HUVECs with LCZ696 and LPS.
- Measurement of intracellular reactive oxygen species (ROS) and malonyl dialdehyde (MDA) levels.
- Assessment of pro-inflammatory cytokine and chemokine expression and secretion.
- Evaluation of cell adhesion molecule expression and monocyte adhesion.
- Analysis of Toll-like receptor 4 (TLR4)/Myd88 pathway activation and nuclear factor kappa-B (NF-κB) translocation.
Main Results:
- LCZ696 significantly attenuated LPS-induced oxidative stress, reducing ROS and MDA levels.
- LCZ696 inhibited the expression and secretion of pro-inflammatory cytokines (IL-6, IL-1α, TNF-β) and chemokines (MCP-1, CXCL1).
- LCZ696 reduced the expression of adhesion molecules (VCAM-1, P-selectin) and suppressed monocyte attachment to HUVECs.
- LCZ696 prevented LPS-induced activation of the TLR4/Myd88 pathway and NF-κB p65 nuclear translocation.
Conclusions:
- LCZ696 demonstrates significant anti-inflammatory properties against LPS-induced endothelial dysfunction.
- LCZ696 protects endothelial cells by mitigating oxidative stress and inhibiting inflammatory signaling pathways.
- These findings suggest LCZ696 has therapeutic potential beyond heart failure treatment, specifically in managing inflammatory cardiovascular conditions.
Abstract:
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-1α (IL-1α), and tumor necrosis factor β (TNF-β) 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-κB) p65 factor. Based on these findings, we conclude that LCZ696 is capable of ameliorating LPS-induced endothelial dysfunction via anti-inflammatory properties.
