Overexpression of semicarbazide-sensitive amine oxidase in smooth muscle cells leads to an abnormal structure of the aortic elastic laminas.
Elevated semicarbazide-sensitive amine oxidase (SSAO) activity has been observed in several human conditions, eg, diabetes, and it has been speculated that SSAO contributes to the development of vasculopathies associated with this disease. To investigate in vivo consequences of elevated expression of SSAO in vascular tissues, we have developed a transgenic model for overexpression of human SSAO in mice. A smooth muscle-specific promoter, smooth muscle alpha-actin promoter 8 (SMP8) was used. Transgenic expression of human SSAO in tissues with a high content of smooth muscle cells was confirmed by Northern blot analysis. Enzymatic analysis of homogenates from transgenic tissues showed elevated levels of SSAO activity compared to non-transgenic littermates. Furthermore, when plasma SSAO activity was analyzed, much higher activity was detected compared to plasma from control mice, indicating that plasma SSAO may originate from smooth muscle cells. Histopathological evaluation of aorta and renal artery from transgenic mice revealed an abnormal structure of the elastin tissue. Instead of the regularly folded elastic laminae normally found in tunica media of sacrificed mice, the elastic laminae were straight and unfolded with irregularly arranged elastic fibers, forming tangled webs, between the intercalating elastic laminae. These alterations of the elastin structures suggest that overexpression of SSAO has led to a reduced elasticity of the arteries. Moreover, the mean femoral arterial pressure of the SMP8 SSAO transgenic mice was significantly lower in comparison to non-transgenic littermates. This suggests that the transgenic mice have a defect in their ability to regulate blood pressure.
Göktürk
Camilla
C
Department of Neuroscience, Uppsala University, Biomedicum, 751-24 Uppsala, Sweden.
Nilsson
Joakim
J
Nordquist
Jenny
J
Kristensson
Millvej
M
Svensson
Kristian
K
Söderberg
Charlotte
C
Israelson
Marianne
M
Garpenstrand
Håkan
H
Sjöquist
Mats
M
Oreland
Lars
L
Forsberg-Nilsson
Karin
K
D006631:Amine Oxidase (Copper-Containing) / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D001158:Arteries / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D015152:Blotting, Northern; D004549:Elastin / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
D004549:Elastin; D006631:Amine Oxidase (Copper-Containing)