Association between semicarbazide-sensitive amine oxidase, a regulator of the glucose transporter, and elastic lamellae thinning during experimental cerebral aneurysm development

Laboratory investigation

Igor Sibon Institut National de la Santé et de la Recherche Médicale U828, Université Victor Segalen Bordeaux 2; and

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Nathalie Mercier Institut National de la Santé et de la Recherche Médicale U684, Université Nancy, France

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Danièle Darret Institut National de la Santé et de la Recherche Médicale U828, Université Victor Segalen Bordeaux 2; and

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Patrick Lacolley Institut National de la Santé et de la Recherche Médicale U684, Université Nancy, France

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Jean-Marie Daniel Lamazière Institut National de la Santé et de la Recherche Médicale U828, Université Victor Segalen Bordeaux 2; and

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Object

Amine oxidases play a key role in the polymerization and cross-linking of the collagens and elastic lamellae of the arterial wall. The loss of elastic lamellae integrity is one of the first steps in the genesis of a cerebral aneurysm. The authors investigated the relation between semicarbazide-sensitive amine oxidase (SSAO) and the organization of the cerebral arterial wall during aneurysm development.

Methods

Intracranial aneurysms were induced in rats via unilateral carotid artery ligation and renovascular hypertension. This modified Hashimoto model was used to create elevated blood pressure associated with shear stress in cerebral arteries. The authors immunohistologically investigated some markers of the extracellular matrix (Types I, III, and IV collagen and elastin), vascular smooth muscle cell differentiation (smooth muscle myosin heavy chain [sm-MHC], α–smooth muscle actin, and desmin), and amine oxidases (SSAO and lysyl oxidase [LOX]) in the cerebral arterial wall in control and treated rats 1, 2, 3, 4, and 6 months after the surgical procedure.

Results

The authors found severe disorganization and thinning of the elastic lamellae and a dramatic reduction in SSAO activity and immunostaining during cerebral aneurysm development. In contrast, LOX markers were slightly increased. Elastic lamellae thinning was highly correlated with decreases in SSAO (r = 0.76, p < 0.0001). There was also a correlation between sm-MHC and SSAO levels.

Conclusions

The data suggested that cerebral hemodynamic modifications induce decreases in SSAO activity resulting in cell dedifferentiation and inducing dysregulation of glucose transport.

Abbreviations used in this paper:

α-SMA = α–smooth muscle actin; ECM = extracellular matrix; ELT = elastic lamellar thickness; GLUT = glucose transporter; LOX = lysyl oxidase; MMP = matrix metalloproteinase; sm-MHC = smooth muscle myosin heavy chain; SMC = smooth muscle cell; SSAO = semicarbazide-sensitive amine oxidase; TGFβ = transforming growth factor–β; VSMC = vascular SMC.
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