TNF‑α regulates apoptosis of human vascular smooth muscle cells through gap junctions

Area of Science:

• Cardiovascular Biology
• Cellular and Molecular Medicine
• Immunology

Background:

• Inflammatory cytokines can induce vascular smooth muscle cell (VSMC) apoptosis, contributing to atherosclerotic plaque rupture.
• Altered connexin (Cx) expression in VSMCs is implicated in the progression of atherosclerosis.

Purpose of the Study:

• To investigate the impact of tumor necrosis factor-alpha (TNF-α) on Cx43 expression and apoptosis in human VSMCs.
• To elucidate the role of Cx43 in TNF-α-induced VSMC apoptosis and its implications for atherosclerotic plaque stability.

Main Methods:

• Human VSMCs were treated with varying concentrations and durations of TNF-α.
• Cx43 expression levels were assessed, and Cx43 plasmid overexpression was utilized.
• Caspase-3 activity and apoptosis rates were measured following TNF-α treatment, with and without a c-Jun N-terminal kinase inhibitor.

Main Results:

• Overexpression of Cx43 plasmids promoted VSMC proliferation.
• TNF-α significantly inhibited Cx43 expression in a dose- and time-dependent manner, an effect reversible by a c-Jun N-terminal kinase inhibitor.
• TNF-α increased caspase-3 activity and VSMC apoptosis, which was linked to the downregulation of Cx43.

Conclusions:

• TNF-α induces apoptosis in VSMCs by downregulating Cx43 expression.
• The inhibition of Cx43 by TNF-α contributes to VSMC apoptosis and subsequent destabilization of atherosclerotic plaques.