Coronary arterioles in type 2 diabetic (db/db) mice undergo a distinct pattern of remodeling associated with decreased vessel stiffness

• Published in: Basic research in cardiology Vol. 106; no. 6; pp. 1123 - 1134
• Main Authors: Katz, Paige S., Trask, Aaron J., Souza-Smith, Flavia M., Hutchinson, Kirk R., Galantowicz, Maarten L., Lord, Kevin C., Stewart, James A., Cismowski, Mary J., Varner, Kurt J., Lucchesi, Pamela A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-11-2011; Springer Nature B.V
• Subjects: Animals; Arterioles - chemistry; Arterioles - metabolism; Arterioles - pathology; Cardiology; Collagen Type I; Coronary Vessels - chemistry; Coronary Vessels - metabolism; Coronary Vessels - pathology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Elasticity - physiology; Elastin - analysis; Elastin - metabolism; Male; Medicine; Medicine & Public Health; Mice; Mice, Mutant Strains; Original Contribution; Reverse Transcriptase Polymerase Chain Reaction; Type 2 diabetes; Matrix; Vascular complications; Remodeling; Coronary flow
• ISSN: 0300-8428; 1435-1803
• DOI: 10.1007/s00395-011-0201-0

Little is known about the impact of type 2 diabetes mellitus (DM) on coronary arteriole remodeling. The aim of this study was to determine the mechanisms that underlie coronary arteriole structural remodeling in type 2 diabetic (db/db) mice. Passive structural properties of septal coronary arterioles isolated from 12- to 16-week-old diabetic db/db and control mice were assessed by pressure myography. Coronary arterioles from 12-week-old db/db mice were structurally similar to age-matched controls. By 16 weeks of age, coronary wall thickness was increased in db/db arterioles (
p
 < 0.01), while luminal diameter was reduced (control: 118 ± 5 μm; db/db: 102 ± 4 μm,
p
 < 0.05), augmenting the wall-to-lumen ratio by 58% (control: 5.9 ± 0.6; db/db: 9.5 ± 0.4,
p
 < 0.001). Inward hypertrophic remodeling was accompanied by a 56% decrease in incremental elastic modulus (
p
 < 0.05, indicating decreased vessel coronary wall stiffness) and a ~30% reduction in coronary flow reserve (CFR) in diabetic mice. Interestingly, aortic pulse wave velocity and femoral artery incremental elastic modulus were increased (
p
 < 0.05) in db/db mice, indicating macrovascular stiffness. Molecular tissue analysis revealed increased elastin-to-collagen ratio in diabetic coronaries when compared to control and a decrease in the same ratio in the diabetic aortas. These data show that coronary arterioles isolated from type 2 diabetic mice undergo inward hypertrophic remodeling associated with decreased stiffness and increased elastin-to-collagen ratio which results in a decreased CFR. This study suggests that coronary microvessels undergo a different pattern of remodeling from macrovessels in type 2 DM.