Abstract
Background & ObjectiveDiabetes mellitus (DM) plays an important role in the pathogenesis of vascular complications including arteriosclerosis and ischemic stroke. Whether DM impacts intracranial aneurysm (IA) formation has not been extensively investigated. In this study, we tested the underlying mechanism of type one DM (T1DM) induced IA formation in rats.Experimental ApproachesT1DM was induced by streptozotocin injection. Rats were euthanized at 0, 4 and 10 weeks after T1DM induction. To evaluate cerebral vascular perfusion, Fluorescein isothiocyanate - dye was injected at 5 min prior to euthanasia. Vascular perfusion was measured by laser scanning confocal microscopy. Trichrome, Elastica van Gieson, alpha-smooth muscle actin (a-SMA) and receptor of advanced glycation end-products (RAGE), toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) immunostaining were performed. The IA formation was classified by 0–3 stages: 0: Normal; 1: Endothelial damage; 2: Moderate protrusion; and 3: Saccular aneurysm formation.ResultsT1DM significantly increased IA formation identified by the classification of aneurysmal changes compared with non-DM rats (p<0.05). However, T1DM induced IA formations were classified as stage 1 and stage 2, but not stage 3. Cerebral vascular perfusion was significantly decreased in T1DM rats compared to non-DM rats (p<0.01). DM10W rats exhibited a significant decrease of cerebral vascular perfusion compared to DM4W rats (p<0.05). T1DM rats also significantly increased the internal carotid artery (ICA) intimae and media thickness, and decreased the internal carotid artery diameter compared to non-DM rats. RAGE, MMP9 and TLR4 expression were significantly increased in T1DM rats compared to non-DM rats. The increased RAGE, TLR4 and MMP9 significantly correlated with IA formation (p<0.05).ConclusionT1DM increases IA formation. The increased RAGE, MMP9 and TLR4 expressions might contribute to IA formation in T1DM rats.
Highlights
Hyperglycemia and diabetes play an important role in the pathogenesis of vascular complications including macroangiopathy and microangiopathy [1], which lead to retinopathy, nephropathy, arteriosclerosis and increased ischemic stroke risk by 2–4 fold relative to those without diabetes [2]
T1DM significantly increased intracranial aneurysm (IA) formation identified by the classification of aneurysmal changes compared with non-Diabetes mellitus (DM) rats (p,0.05)
We found that T1DM significantly increased aneurysmal formation identified by the classification of aneurysmal changes compared with non-DM rats (Figure 1A–C)
Summary
Hyperglycemia and diabetes play an important role in the pathogenesis of vascular complications including macroangiopathy and microangiopathy [1], which lead to retinopathy, nephropathy, arteriosclerosis and increased ischemic stroke risk by 2–4 fold relative to those without diabetes [2]. Diabetes mellitus (DM) induces vascular endothelial damage and dysfunction, decreases cerebral tight junction protein expression [3], and promotes artery intima-media thickness (IMT) [4] and atherosclerotic vascular disease. Endothelial damage [5] and reduction of tight junction protein expression are related with cerebral aneurysm formation [6]. Diabetes mellitus (DM) plays an important role in the pathogenesis of vascular complications including arteriosclerosis and ischemic stroke. We tested the underlying mechanism of type one DM (T1DM) induced IA formation in rats. The IA formation was classified by 0–3 stages: 0: Normal; 1: Endothelial damage; 2: Moderate protrusion; and 3: Saccular aneurysm formation
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