Role of elevated EGFR phosphorylation in the induction of structural remodelling and altered mechanical properties of resistance artery from type 2 diabetic mice

Background Type 2 diabetes is associated with microvascular complications. We hypothesized that the sustained elevated EGFR phosphorylation produces structural wall remodelling and altered mechanical properties of mesenteric resistance artery (MRA) in type 2 diabetes. Methods Freshly isolated MRA (80–100 µm diameter) from type 2 diabetic (db − /db − , diabetic) and non‐diabetic (db − /db + , control) mice were subjected to pressure‐passive diameter and wall thickness relationships; western blot analysis and immunohistology. Results Data indicated that MRA from diabetic mice have a smaller passive diameter than MRA from control mice under intra‐luminal pressure range from 25 to 125 mmHg. Measurements of wall thickness : lumen diameter ratios (21 ± 1.8 vs 14 ± 1.2 at 75 mmHg diabetic vs control, respectively), wall thickness and remodelling index (38 ± 5% vs control) revealed eutrophic structural remodelling of MRA from diabetic mice, which was strengthened with histology. Mechanical properties revealed a great strain‐stress relationship in MRA from control versus diabetic mice indicating increased stiffness in MRA from diabetic mice. Western blot analysis showed increased collagen type 1 content in a freshly isolated MRA from the type 2 diabetic mice when compared to control mice. Diabetic mice treated with EGFR inhibitor (AG1478, 10 mg/kg/day) for 2 weeks showed reduced EGFR phosphorylation, wall thickness, collagen type 1 content, and improved the altered mechanical properties of MRA. Conclusion These data provide evidence regarding the role of EGFR in morphological wall remodelling and altered mechanical properties of MRA from type 2 diabetic mice. This may identify new therapeutic targets for the control of vascular structure and therefore have important implications in type 2 diabetes. Copyright © 2008 John Wiley & Sons, Ltd.