Macrovascular changes in mice overexpressing human semicarbazide-sensitive amine oxidase in smooth muscle cells.
BACKGROUND
The catalytic activity of semicarbazide-sensitive amine oxidase (SSAO) is increased in diabetes, as well as in other disorders of cardiovascular origin. Our hypothesis is that SSAO is involved in the synthesis or maturation of elastin in vascular tissue. An increased SSAO activity can thereby be involved in the development of vascular damage.


METHODS
Elastin quantification was performed in aorta of transgenic mice overexpressing the human form of SSAO, using electron microscopy. Furthermore, lung capacity was measured using a spirometry-mimicking method, developed for mice. The effect of vasoactive substances was estimated by measuring mean arterial pressure and pulse pressure under anesthesia.


RESULTS
No differences in elastin quantity or lung capacity could be observed between transgenic or nontransgenic littermates. Pulse pressure was higher in transgenic mice, and electron microscopy of aorta showed elastin fibers parallel with the aorta wall (ie, straight fibers instead of folded compared with control mice). No difference in the response to adrenaline or sodium chloride was observed between the transgenic and control mice. The control mice had a clear decrease in blood pressure (BP) with a longer duration as a response to injection of a nitric oxide (NO) donor, sodium nitroprusside, compared with transgenic mice where only a minor response was observed. The SSAO activity in serum of control mice was elevated in response to injection of the NO donor, but not in response to a ganglion blocker.


CONCLUSIONS
An elevated pulse pressure, together with an abnormal elastin structure in the aorta, suggests a rigidity of large arteries as a result of an elevated SSAO activity as well as a physiologic role for SSAO in elastin maturation.
Gokturk
Camilla
C
Section of Pharmacology, Department of Neuroscience, Uppsala, Sweden. Camilla.Gokturk@neuro.uu.se
Sugimoto
Haruyo
H
Blomgren
Bo
B
Roomans
Godfried M
GM
Forsberg-Nilsson
Karin
K
Oreland
Lars
L
Sjoquist
Mats
M
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000502:physiology* / Q000648:ultrastructure; D001794:Blood Pressure / Q000502:physiology*; D004548:Elasticity; D004549:Elastin / Q000378:metabolism*; D005260:Female; D006339:Heart Rate; D008168:Lung / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000502:physiology; D011674:Pulse; D012119:Respiration
D004549:Elastin; D006631:Amine Oxidase (Copper-Containing)