Pro-inflammatory angiogenesis is mediated by p38 MAP kinase

Area of Science:

• Endothelial cell biology
• Inflammation and disease
• Angiogenesis research

Background:

• Chronic inflammation and endothelial dysfunction are linked to diseases.
• Aberrant angiogenesis is a hallmark of many inflammatory conditions.
• Understanding endothelial cell signaling in inflammation is crucial.

Purpose of the Study:

• To investigate endothelial cell signaling pathways in chronic inflammation.
• To elucidate the role of p38 MAP kinase in pro-inflammatory angiogenesis.
• To determine the relationship between oxidative stress, TNF, and angiogenesis.

Main Methods:

• In vitro capillary sprout formation assay with activated endothelial cells (TNF, H2O2, transmembrane TNF).
• Analysis of signaling pathways including p38 MAP kinase, NADPH oxidase, and MMPs.
• In vivo study using a prostate tumor model with pharmacological p38 MAP kinase inhibition.

Main Results:

• Continuous endothelial activation promoted angiogenesis dependent on p38 MAP kinase, NADPH oxidase, and MMPs.
• Activated endothelial cells showed increased ROS production and TNF expression, forming a positive feedback loop.
• p38 MAP kinase exhibited a pro-angiogenic role in activated cells, contrasting its anti-angiogenic role in unstimulated cells.
• Inhibition of p38 MAP kinase reduced prostate tumor growth and tumor vessel density in vivo.

Conclusions:

• Continuous endothelial cell activation switches p38 MAP kinase from anti-angiogenic to pro-angiogenic activity.
• This switch is associated with oxidative stress and autocrine TNF production.
• p38 MAP kinase plays a critical role in pathological angiogenesis in vivo.