Angiotensin-converting enzyme inhibitors downregulate tissue factor synthesis in monocytes

Area of Science:

• Cardiovascular Medicine
• Hematology
• Pharmacology

Background:

• Tissue factor (TF) initiates blood coagulation and is crucial in arterial thrombosis following atherosclerotic plaque rupture.
• Monocytes express TF and components of the renin-angiotensin system, suggesting a link between coagulation and this system.

Purpose of the Study:

• To investigate whether ACE inhibitors can modulate TF expression in monocytes.
• To explore the potential therapeutic implications of this modulation for thrombotic events.

Main Methods:

• Mononuclear leukocytes from healthy volunteers were stimulated with endotoxin in the presence or absence of ACE inhibitors.
• TF expression was measured using a 1-stage clotting assay and ELISA.
• TF mRNA levels and nuclear factor-kappaB translocation were assessed via RT-PCR and other molecular techniques.

Main Results:

• Captopril reduced endotoxin-induced TF expression in mononuclear leukocytes by approximately 60% in a dose-dependent manner.
• Other ACE inhibitors and an angiotensin II AT(1) receptor antagonist (losartan) demonstrated comparable reductions in TF activity.
• ACE inhibitors were found to inhibit endotoxin-mediated increases in TF mRNA and nuclear factor-kappaB translocation to the TF gene promoter.

Conclusions:

• ACE inhibitors and angiotensin II AT(1) antagonists can modulate TF expression in mononuclear cells.
• This modulation of TF expression may contribute to the anti-ischemic effects of these drugs.
• The findings have significant biological and therapeutic implications for understanding and managing thrombotic processes.