Endogenous adrenomedullin protects against vascular response to injury in mice.

Abstract

BACKGROUND:

In our previous study, adrenomedullin (AM) overexpression could limit the arterial intimal hyperplasia induced by cuff injury in rats. However, it remains to be elucidated whether endogenous AM plays a role against vascular injury.

METHODS AND RESULTS:

We used the AM knockout mice to investigate the effect of endogenous AM. Compared with wild-type (AM+/+) mice, heterozygous AM knockout (AM+/-) mice had the increased intimal thickening of the cuff-injured femoral artery, concomitantly with lesser AM staining. In AM+/- mice, cuff placement increased both the production of superoxide anions (O2-) measured by coelentarazine chemiluminescence and the immunostaining of p67phox and gp91phox, subunits of NAD(P)H oxidase in the adventitia, associated with the increment of CD45-positive leukocytes, suggesting that the stimulated formation of radical oxygen species accompanied chronic adventitial inflammation. Not only the AM gene transfection but also the treatment of NAD(P)H oxidase inhibitor apocynin and membrane-permeable superoxide dismutase mimetic tempol could limit cuff-induced intimal hyperplasia in AM+/- mice, associated with the inhibition of O2- formation in cuff-injured artery.

CONCLUSIONS:

The overproduction of oxidative stress induced by the increased NAD(P)H oxidase activity might be involved in cuff-injured arterial intimal hyperplasia in AM+/- mice. Thus, it is suggested that endogenous AM possesses a protective action against the vascular response to injury, possibly through the inhibition of oxidative stress production.

• Authors: Junsuke Kawai, Katsuyuki Ando, Akihiro Tojo, Tatsuo Shimosawa, Katsutoshi Takahashi, Maristela Lika Onozato, Masao Yamasaki, Teruhiko Ogita, Takashi Nakaoka, Toshiro Fujita
• Journal: Circulation (Circulation) Vol. 109 Issue 9 Pg. 1147-53 (Mar 09 2004) ISSN: 1524-4539 [Electronic] United States
• PMID: 14769703 (Publication Type: Journal Article)

Chemical References

• Acetophenones
• Cyclic N-Oxides
• Enzyme Inhibitors
• Membrane Glycoproteins
• Peptides
• Phosphoproteins
• Spin Labels
• neutrophil cytosol factor 67K
• Superoxides
• Adrenomedullin
• acetovanillone
• CYBB protein, human
• NADPH Oxidase 2
• NADPH Oxidases
• Leukocyte Common Antigens
• tempol

Topics

• Acetophenones (pharmacology)
• Adrenomedullin
• Animals
• Arterial Occlusive Diseases (etiology, metabolism, pathology)
• Cell Movement
• Cyclic N-Oxides (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Femoral Artery (chemistry, metabolism, pathology)
• Hyperplasia
• Leukocyte Common Antigens (analysis)
• Leukocytes (physiology)
• Membrane Glycoproteins (analysis)
• Mice
• Mice, Knockout
• NADPH Oxidase 2
• NADPH Oxidases (analysis, antagonists & inhibitors)
• Oxidative Stress
• Peptides (analysis, genetics, physiology)
• Phosphoproteins (analysis)
• Spin Labels
• Superoxides (metabolism)
• Tunica Intima (pathology)