Dataset Information

Diabetes-mediated middle cerebral artery remodeling is restored by linagliptin: Interaction with the vascular smooth muscle cell endothelin system.

ABSTRACT: Endothelin-1 (ET-1) mediates cerebrovascular remodeling in vascular smooth muscle layer of the middle cerebral arteries (MCA) in type-2 diabetic Goto-Kakizaki (GK) rats. While metformin, oral glucose lowering agent, prevent/restores vascular remodeling and reduce systemic and local ET-1 levels whether this effect was specific to metformin remained unknown. Our working hypotheses were 1) linagliptin, a DPP-IV inhibitor, can reverse diabetes-mediated cerebrovascular remodeling and this is associated with decreased ET-1, and 2) linagliptin prevents the high glucose induced increase in ET-1 and ET receptors in brain vascular smooth muscle cells (bVSMCs).Diabetic and non-diabetic GK rats were treated with linagliptin (4weeks). MCAs were fixed in buffered 4% paraformaldehyde and used for morphometry. Human bVSMCs incubated in normal glucose (5.5mM)/high glucose (25mM) conditions were treated with the linagliptin (100nM; 24h). ET-1 secretion and ET receptors were measured in media and cell lysate respectively. Immunostaining was performed for ET-A and ET-B receptor. ET receptors were also measured in cells treated with ET-1 (100nM) and linagliptin.Linagliptin treatment regressed vascular remodeling of MCAs in diabetic animals but had no effect on blood glucose. bVSMCs in normal/high glucose condition did not show any significant difference in ET-1 secretion or ET-A and ET-B receptor expression. ET-1 treatment in high glucose condition significantly increased the ET-A receptors and this effect was inhibited by linagliptin.Linagliptin is effective in reversing established pathological cerebrovascular remodeling associated with diabetes. Attenuation of the ET system could be a pleiotropic effect of linagliptin that provides vascular protection.

SUBMITTER: Yasir A

PROVIDER: S-EPMC4992649 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundArterial compliance (AC) and vascular resistance (VR) are crucial for the regulation capacity of the vascular system. However, alterations of these features and hemodynamics due to atherosclerosis in a single intracranial artery territory have not been extensively investigated. Thus this study aimed to examine the AC, VR, and hemodynamic variations due to plaque and infarction in the middle cerebral artery (MCA).MethodsPatients with symptomatic MCA atherosclerosis were recruited. Both sides of the MCA were assessed and then classified according to the following scheme: group 0, without plaque; group 1, with plaque but without infarct; group 2, with plaque and infarct in the supplying territories. Data on AC, VR, blood flow, and pulsatility index (PI) were obtained based on 4D flow magnetic resonance imaging (MRI) and the Windkessel model.ResultsA total of 63 patients were recruited. After 17 MCAs were excluded (occlusion, n=6; poor image quality, n=11), datasets on 109 MCAs were finally collected and classified into group 0 (n=39), group 1 (n=40), and group 2 (n=30). From groups 0 to 2, there was a decrease in AC (0.0060±0.0031 vs. 0.0052±0.0029 vs. 0.0026±0.0020 mL/mmHg) and an increase in VR [28.65±16.11 vs. 42.59±27.53 vs. 63.21±40.37 mmHg/(mL/s)]. Compared to group 1, group 2 had significantly decreased AC (0.0052±0.0029 vs. 0.0026±0.0020 mL/mmHg; P=0.003) and increased VR [42.59±27.53 vs. 63.21±40.37 mmHg/(mL/s); P=0.021]. From group 0 to group 2, there was a decrease in blood flow (179.29±73.57 vs. 125.11±59.04 vs. 92.05±48.79 mL/min; P<0.001). The PI varied significantly among the 3 groups (0.86±0.20 vs. 1.12±0.50 vs. 0.79±0.16; P<0.001), with group 1 having the highest PI.ConclusionsWith the occurrence of plaque and infarct, AC and blood flow progressively decrease while VR increases. The PI was the highest in the group with plaque and without infarct. Assessments of vascular function and hemodynamics in a single artery territory can clarify comprehensive alterations in the cerebral vascular system (CVS).

Dataset Information

Diabetes-mediated middle cerebral artery remodeling is restored by linagliptin: Interaction with the vascular smooth muscle cell endothelin system.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets