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Natriuretic peptides regulate the expression of tissue factor and PAI-1 in endothelial cells
M Yoshizumi1, H Tsuji, H Nishimura
1Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan. yoshizum@dc4.so-net.ne.jp
Insights
Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) regulate blood coagulation by suppressing angiotensin II-induced tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) expression.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Hemostasis and Thrombosis
Background:
- Angiotensin II (Ang II) plays a critical role in regulating blood pressure and fluid balance.
- Ang II can induce pro-coagulant and anti-fibrinolytic factors, potentially contributing to thrombotic events.
- Natriuretic peptides, including BNP and CNP, are known for their vasodilatory and diuretic effects.
Purpose of the Study:
- To investigate the interaction between natriuretic peptides (BNP and CNP) and Ang II in the regulation of blood coagulation and fibrinolysis.
- To determine the effect of BNP and CNP on Ang II-induced expression of key hemostatic factors.
Main Methods:
- Analysis of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) mRNA expression using northern blotting.
- Measurement of TF activity on rat aortic endothelial cells (RAECs) via chromogenic assay.
- Quantification of PAI-1 activity in culture media using chromogenic assay.
Main Results:
- BNP and CNP significantly suppressed Ang II-induced TF and PAI-1 mRNA expression in a time- and concentration-dependent manner.
- The suppression of mRNA expression by BNP and CNP was mediated via the cyclic guanosine monophosphate (cGMP) cascade.
- These suppressions were associated with decreased TF and PAI-1 activities.
- Neither TFPI nor TPA mRNA expression was affected by BNP and CNP treatment.
Conclusions:
- BNP and CNP exert anticoagulant and profibrinolytic effects by inhibiting Ang II-mediated TF and PAI-1 induction.
- The cGMP pathway is involved in the inhibitory actions of BNP and CNP on TF and PAI-1 expression.
- These findings highlight a novel interaction between natriuretic peptides and the renin-angiotensin system in hemostasis regulation.
Abstract:
In the present study, we demonstrate that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) interact with angiotensin II (Ang II) in regulative blood coagulation and fibrinolysis by suppressing the expressions of both tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by Ang II. The expressions of TF and PAI-1 mRNA were analyzed by northern blotting methods, and the activities of TF on the surface of rat aortic endothelial cells (RAECs) and PAI-1 in the culture media were respectively measured by chromogenic assay. Both BNP and CNP suppressed the expressions of TF and PAI-1 mRNA induced by Ang II in a time- and concentration-dependent manner via cGMP cascade, which suppressions were accompanied by respective decrease in activities of TF and PAI-1. However, neither the expression of tissue factor pathway inhibitor (TFPI) nor tissue-type plasminogen activator (TPA) mRNA was affected by the treatment of BNP and CNP.