N-Acetyl Cysteine Protects Vascular Endothelial Cells Against LPS-Induced Inflammation via NF-κB Pathway

This in vitro study exposed human umbilical vein endothelial cells (HUVECs) to lipopolysaccharide (LPS) to induce inflammatory injury, then assessed whether N-acetyl cysteine (NAC) pre-treatment protected against the inflammatory response through the NF-κB signaling pathway.

NAC significantly reduced LPS-induced expression of pro-inflammatory mediators — IL-8, TNF-α, nitric oxide (NO), iNOS, and ICAM-1 — and inhibited phosphorylation of NF-κB p65. The findings indicate that NAC attenuates LPS-induced vascular endothelial inflammation by blocking NF-κB activation.

NAC is a glutathione precursor and antioxidant with multiple proposed mechanisms relevant to cardiovascular risk: antioxidant properties (free radical scavenging), NO metabolism (influencing vasodilation), and anti-inflammatory effects through NF-κB suppression. The in vitro anti-inflammatory finding is mechanistically plausible and consistent with NAC’s known antioxidant mechanism.

The gap between in vitro cell culture results and clinical cardiovascular outcome evidence is substantial. LPS-induced endothelial inflammation in cell culture is a model for acute inflammatory injury, not the chronic low-grade atherosclerotic inflammation of clinical CAD. Human randomized trial evidence for NAC’s effect on cardiovascular events is limited, and NAC has not been validated as a cardiovascular prevention strategy in outcome trials.

We rate the evidence limited. An in vitro study demonstrating NAC’s anti-inflammatory effect in LPS-stimulated endothelial cells via NF-κB suppression — mechanistic cell biology with no direct translation to cardiovascular outcome evidence.