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(Circulation Research. 2004;95:50.)
© 2004 American Heart Association, Inc.

Molecular Medicine

Origins of Serum Semicarbazide-Sensitive Amine Oxidase

Craig M. Stolen, Gennady G. Yegutkin, Riikka Kurkijärvi, Petri Bono, Kari Alitalo, Sirpa Jalkanen

From the MediCity Research Laboratory (C.M.S., G.G.Y., R.K., S.J.), University of Turku and National Public Health Institute, Turku, Finland; the Department of Oncology (P.B.), Helsinki University Central Hospital, Helsinki, Finland; and the Molecular/Cancer Biology Laboratory (K.A.), University of Helsinki, Helsinki, Finland.

Correspondence to Craig M. Stolen, PhD, MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520, Turku, Finland. E-mail craig.stolen{at}utu.fi

Semicarbazide-sensitive amine oxidases (SSAO) are enzymes that are capable of deaminating primary amines to produce aldehyde, ammonia, and hydrogen peroxide. This activity has been associated with vascular adhesion protein-1 (VAP-1) and is found in the serum, endothelium, adipose, and smooth muscle of mammals. Circulating SSAO activity is increased in congestive heart failure, diabetes, and inflammatory liver diseases. To investigate the origin of circulating SSAO activity, two transgenic mouse models were created with full-length human VAP-1 (hVAP-1) expressed on either endothelial (mTIEhVAP-1) or adipose tissues (aP2hVAP-1), with tie-1 and adipocyte P2 promoters, respectively. Under normal conditions a circulating form of hVAP-1 was found at high levels in the serum of mice with endothelium-specific expression and at low levels in the serum of mice with adipose specific expression. The level of circulating hVAP-1 in the transgenic mice varied with gender, transgene zygosity, diabetes, and fasting. Serum SSAO activity was absent from VAP-1 knockout mice and endothelial cell–specific expression of human VAP-1 restored SSAO activity to the serum of VAP-1 knockout mice. Together, these experiments show that in the mouse VAP-1 is the only source of serum SSAO, that under physiological conditions vascular endothelial cells can be a major source of circulating VAP-1 protein and SSAO, and that serum VAP-1 can originate from both endothelial cells and adipocytes during experimental diabetes. An increased endothelial cell capacity for lymphocyte binding and altered expression of redox-sensitive proteins was also associated with the mTIEhVAP-1 transgene.

Key Words: diabetes • hydrogen peroxide • transgenic mice • vascular disease • vascular endothelium

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