Progressive Coronary Artery Remodeling in Diabetic db/db Mice

Abstract

Type 2 diabetes is associated with vascular dysfunction and remodeling. The aim of this study was to determine the progression of coronary artery remodeling in Type 2 diabetes. Septal coronary arteries from 12, 16, and 20‐wk‐old heterozygous Db/db and Type 2 diabetic db/db mice were isolated and mounted on a pressure myograph containing Ca2+‐free physiological saline solution, EGTA and sodium nitroprusside. Passive structural measurements across a range of pressures revealed no changes in coronary structure in 12‐wk db/db mice, a time at which endothelial dysfunction is reported. However, wall thickness in diabetic arteries at 16 and 20‐wks was augmented (Db/db‐16: 6.9±0.6 μm vs. db/db‐16: 9.7±0.5 μm and Db/db‐20 6.7±0.8 μm vs. db/db‐20 9.2±0.7 μm at 100 mmHg, p < 0.05, respectively) while internal lumen diameters tended to be reduced (Db/db‐16: 117.6±4.6 μm vs. db/db‐16: 102.9±4.3 μm and Db/db‐20 112.3±9.1 μm vs. db/db‐20 106.2±6.7 μm at 100 mmHg). The wall/lumen ratio at the same ages was augmented in diabetic coronary arteries (Db/db‐16: 6.0±0.6 μm vs. db/db‐16: 9.5±0.4 μm and Db/db‐20 6.1±0.6 μm vs. db/db‐20 8.9±0.7 μm at 100 mmHg, p < 0.01). Despite these structural changes, no change in compliance was observed between control and diabetic groups. These data indicate that diabetic coronary arteries undergo progressive inward remodeling that may lead to impaired cardiac perfusion and coronary flow reserve. Supported by NIH RO1‐HL056046 (PAL).