Substance P ameliorates tumor necrosis factor-alpha-induced endothelial cell dysfunction by regulating eNOS...

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Biology
• Inflammation Research

Background:

• Inflammation poses a significant threat to vascular endothelium integrity.
• Tumor Necrosis Factor-alpha (TNF-α) is a key mediator in inflammation-induced endothelial cell death.
• Nitric Oxide (NO) plays a crucial role in maintaining endothelial cell survival.

Purpose of the Study:

• To investigate the protective effects of SP on endothelial cells against TNF-α-induced damage.
• To elucidate the role of SP in modulating nitric oxide (NO) production.
• To explore the impact of SP on inflammation-related endothelial cell death.

Main Methods:

• Human Umbilical Vein Endothelial Cells (HUVECs) were treated with TNF-α to induce an inflammatory environment.
• SP was administered prior to TNF-α to assess its protective potential.
• Cell viability was measured using WST-1 assay.
• NO levels were quantified using the Griess Reagent System.
• Western blot analysis was employed to detect key proteins like cleaved caspase-3, eNOS, and phosphorylated Akt.

Main Results:

• TNF-α significantly reduced endothelial cell viability and NO production, while downregulating Akt phosphorylation.
• SP pretreatment attenuated TNF-α-induced apoptosis, preserving cell viability.
• SP treatment led to increased NO production, enhanced Akt phosphorylation, and elevated eNOS expression.
• The protective effects of SP were dependent on the Akt/eNOS/NO pathway, as confirmed by blockage experiments.

Conclusions:

• SP demonstrates significant protective effects against inflammation-induced vascular endothelial damage.
• SP modulates the Akt/eNOS/NO signaling pathway to promote endothelial cell survival.
• These findings highlight SP as a potential therapeutic agent for vascular inflammation.