Apremilast ameliorates ox-LDL-induced endothelial dysfunction mediated by KLF6

Area of Science:

• Cardiovascular Biology
• Inflammation Research
• Pharmacology

Background:

• Apremilast (a PDE4 inhibitor) treats inflammatory conditions like psoriasis.
• Atherosclerosis involves chronic inflammation and endothelial dysfunction.
• Therapies addressing both psoriasis and atherosclerosis are of interest.

Purpose of the Study:

• To investigate apremilast's effects on human aortic endothelial cells (HAECs) in an atherosclerosis model.
• To determine if apremilast modulates key molecular pathways in atherosclerosis.

Main Methods:

• HAECs were exposed to oxidized low-density lipoprotein (ox-LDL) to mimic atherosclerosis.
• The expression of LOX-1, inflammatory cytokines (TNF-α, IL-6, IL-8), and adhesion molecules (VCAM-1, MCP-1) was analyzed.
• Monocyte (U937) attachment to HAECs was measured.
• The role of Krüppel-like factor 6 (KLF6) and JNK signaling was assessed.

Main Results:

• Apremilast reduced lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1) expression.
• Apremilast inhibited pro-atherosclerotic inflammatory cytokines (TNF-α, IL-6, IL-8).
• Apremilast decreased monocyte adhesion to HAECs by downregulating MCP-1 and VCAM-1, mediated by KLF6 rescue via JNK pathway modulation.

Conclusions:

• Apremilast demonstrates anti-inflammatory and anti-atherosclerotic properties in vitro.
• It may mitigate endothelial dysfunction and monocyte infiltration characteristic of atherosclerosis.
• These findings support further investigation of apremilast as a potential treatment for atherosclerosis.