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- Gokturk, Camilla, et al.
(författare)
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Macrovascular changes in mice overexpressing human semicarbazide-sensitive amine oxidase in smooth muscle cells
- 2007
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 20:7, s. 743-750
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Göktürk, Camilla, et al.
(författare)
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Semicarbazide-sensitive amine oxidase in transgenic mice with diabetes
- 2004
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 325:3, s. 1013-1020
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Tidskriftsartikel (refereegranskat)abstract
- Semicarbazide-sensitive amine oxidase (SSAO) activity in plasma is increased in diabetes, and in particular, in diabetic patients with vascular complications. It has been speculated that SSAO is involved in the development of such complications due to the production of cytotoxic compounds. In this work, we have induced diabetes in a previously described mouse-model, overexpressing SSAO in smooth muscle cells. SSAO activity was estimated as well as expression of the endogenous mouse gene and human transgene using real-time PCR. Diabetes induced an increase in SSAO activity in serum, kidney, and adipose tissue of transgenic animals. An inverse correlation between SSAO activity and mouse SSAO mRNA levels was observed in transgenic animals with diabetes. These results further support the suggestion of a negative feedback control of the SSAO gene expression. The increased SSAO activity in diabetes is most likely dependent on post-transcriptional modifications or activation of existing inactive enzyme molecules.
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| 3. |
- Göktürk, Camilla, 1967-
(författare)
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Semicarbazide-sensitive Amine Oxidase (SSAO) – Regulation and Involvement in Blood Vessel Damage with Special Regard to Diabetes : A Study on Mice Overexpressing Human SSAO
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Semicarbazide-sensitive amine oxidase (SSAO, EC 1.4.3.6) belongs to a family of copper-containing amine oxidases. SSAO exists as a membrane bound protein in endothelial-, smooth muscle-, and adipose cells as well as soluble in plasma. SSAO catalyses oxidative deamination of primary monoamines, which results in the production of corresponding aldehydes, hydrogen peroxide and ammonia. These compounds are very reactive and potentially cytotoxic, and are able to induce vascular damage if produced in high levels. Patients with diabetes mellitus, and with diabetic complications in particular, have a higher SSAO activity in plasma compared to healthy controls. It has therefore been speculated that high SSAO activity is involved in the development of vascular complications associated with diabetes. The aim of this thesis is to investigate the importance of SSAO in the development of disorders of a vascular origin. We have studied the transcriptional regulation of the SSAO gene, by inducing diabetes in NMRI and in transgenic mice, overexpressing the human form of SSAO in smooth muscle cells. We found that the increase in SSAO activity in diabetes is accompanied by reduced mRNA levels of the endogenous mouse gene, suggesting a negative feedback on the transcription of the SSAO gene. In addition, the transgenic mice exhibited an abnormal phenotype in the elastic tissue of aorta and renal artery. These mice have a lower mean artery pressure and an elevated pulse pressure. These results indicate that high SSAO activity in smooth muscle cells is associated with a change in the morphology of large arteries. This is likely contributing to the development of vascular complications in diabetes.
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