Histamine induces tissue factor expression: implications for acute coronary syndromes.

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cell Signaling

Background:

• Histamine is known to cause coronary vasospasm, contributing to variant angina and myocardial infarction.
• The specific role of histamine in thrombus formation remains unclear.
• This study investigates histamine's potential to induce tissue factor (TF) expression in vascular cells.

Purpose of the Study:

• To determine if histamine induces tissue factor (TF) expression in human aortic endothelial and vascular smooth muscle cells.
• To elucidate the receptor pathways and intracellular signaling cascades involved in histamine-induced TF expression.
• To explore the implications for conditions like variant angina and acute coronary syndromes.

Main Methods:

• Human aortic endothelial and vascular smooth muscle cells were treated with histamine.
• Tissue factor (TF) and TF pathway inhibitor expression were assessed using RT-PCR and Northern blotting.
• MAP kinase (p38, ERK, JNK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways were investigated.
• Receptor antagonism (H1 and H2) and specific kinase inhibition were employed.

Main Results:

• Histamine induced TF expression in a concentration-dependent manner via H1 receptors, but not H2 receptors.
• Histamine stimulated TF mRNA and protein expression, increasing surface activity.
• This effect was mediated by the activation of p38, ERK, and JNK MAP kinases.
• PI3K inhibition enhanced histamine-induced TF expression, while Rho-kinase inhibition had no effect.

Conclusions:

• Histamine induces TF expression in vascular cells through H1 receptor activation.
• The signaling pathway involves p38, ERK, and JNK MAP kinases.
• These findings suggest a novel mechanism linking histamine to thrombosis and offer potential therapeutic targets for cardiovascular events.