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C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of

Ramona S Scotland1, Marc Cohen, Paul Foster

  • 1Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London WC1E 6AE, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|September 24, 2005
PubMed

Insights

C-type natriuretic peptide (CNP) reduces inflammation by inhibiting immune cell and platelet activation in blood vessels. This peptide may offer a therapeutic target for cardiovascular disorders.

Area of Science:

  • Cardiovascular Research
  • Inflammation Biology
  • Endothelial Cell Biology

Background:

  • Immune cell recruitment is crucial for inflammation and cardiovascular disease pathogenesis.
  • C-type natriuretic peptide (CNP) is an endothelium-derived mediator regulating vascular tone and protecting against ischemia/reperfusion injury.

Purpose of the Study:

  • To investigate if CNP inhibits leukocyte recruitment and platelet aggregation.
  • To determine CNP's anti-inflammatory influence on the blood vessel wall.

Main Methods:

  • Assessed CNP effects on leukocyte-endothelial cell interactions in mouse mesenteric venules in vivo.
  • Utilized endothelial nitric oxide synthase knockout (eNOS(-/-)) mice and IL-1beta/histamine-induced inflammation models.
  • Examined CNP's impact on platelet aggregation and P-selectin expression in human blood and endothelial cells.

Main Results:

  • CNP rapidly suppressed leukocyte rolling in eNOS(-/-) mice and IL-1beta/histamine-induced inflammation.
  • CNP inhibited platelet-leukocyte interactions and thrombin-induced platelet aggregation.
  • CNP selectively attenuated P-selectin expression on endothelial cells, leukocytes, and platelets.

Conclusions:

  • CNP modulates acute inflammation in the blood vessel wall by inhibiting leukocyte and platelet activation.
  • CNP's anti-inflammatory effects are partly mediated by suppressing P-selectin expression.
  • Endothelial CNP may possess anti-atherogenic properties and represent a therapeutic target for cardiovascular disorders.

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