Receptor for advanced glycation end products is involved in remodeling of diabetic coronary arterioles

Abstract

The aim of this study was to determine whether the receptor for advanced glycation end products (RAGE) contributes to remodeling of type 2 diabetic coronary arterioles (<150 μm diameter) of leptin‐receptor deficient db/db mice. Coronary arterioles isolated from control Db/db, type 2 diabetic db/db, and RAGE−/− × db/db mice at 16 weeks of age were mounted on a pressure myograph to measure and record wall thickness and diameters over a range of pressures (0–125 mmHg). Coronary arterioles isolated from db/db mice exhibited decreased luminal diameter (Db/db: 118 ± 5 μm vs. db/db: 103 ± 4 μm p < 0.05) with thicker microvascular walls (Db/db: 6.9 ± 0.6 μm vs. db/db: 9.7 ± 0.5 μm p < 0.01), which significantly increased the wall:lumen ratio (Db/db: 6.0 ± 0.8 vs. db/db: 9.5 ± 0.4, p < 0.01). Compared to db/db mice, coronary arterioles isolated from RAGE−/−x db/db mice had similar internal diameter (104 ± 9 μm, p > 0.05), while wall thickness (6.1 ± 0.5 μm, p < 0.001), wall:lumen ratio (6.2 ± 0.8 μm, p < 0.01), and growth index (db/db: 28.1 vs. RAGE−/−x db/db: 22.3, % of control) were reduced. External diameters were not different among groups, although there was a tendency for reduced external diameter in RAGE−/−x db/db. These data suggest that the RAGE receptor is at least partially responsible for inward hypertrophic remodeling observed in coronary arterioles of type 2 diabetic mice.Support: NIH T32HL098039 to AJT; NIH HL056046 to PAL.