Endothelial RIG-I activation impairs endothelial function.

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Medicine

Background:

• Endothelial dysfunction is central to atherosclerosis, involving immune mechanisms.
• Pattern recognition receptors (PRRs) recognizing nucleic acids are implicated in endothelial biology.
• The role of retinoic acid inducible gene I (RIG-I) in endothelial cells requires further investigation.

Purpose of the Study:

• To investigate the impact of endothelial RIG-I activation on vascular endothelial biology.
• To elucidate the mechanisms by which RIG-I influences endothelial cells in a proatherogenic context.

Main Methods:

• In vivo studies involved intravenous injection of RIG-I ligand (3pRNA) or control in wild type mice.
• In vitro studies utilized cultured human coronary artery endothelial cells (HCAEC) and endothelial progenitor cells (EPC) stimulated with 3pRNA.
• Assessed vascular function, oxidative stress, endothelial microparticles (EMP), reactive oxygen species (ROS), apoptosis, proliferation, and cytokine release.

Main Results:

• 3pRNA treatment in mice led to impaired vasodilation, increased vascular oxidative stress, and elevated EMP levels.
• Both HCAEC and EPC express RIG-I, upregulating it upon stimulation.
• RIG-I activation enhanced ROS formation in both cell types and induced proinflammatory cytokine release from HCAEC.

Conclusions:

• Activation of the cytoplasmic nucleic acid receptor RIG-I induces endothelial dysfunction.
• RIG-I-mediated endothelial damage represents a significant pathway in atherogenesis.
• Targeting RIG-I may offer a novel therapeutic strategy for preventing or treating atherosclerosis.