title: Coronary arterioles in type 2 diabetic (db/db) mice undergo a distinct pattern of remodeling associated with decreased vessel stiffness.
abstract: 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.
authors: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors: Paige S
authors: PS
authors: Katz
authors: Aaron J
authors: AJ
authors: Trask
authors: Flavia M
authors: FM
authors: Souza-Smith
authors: Kirk R
authors: KR
authors: Hutchinson
authors: Maarten L
authors: ML
authors: Galantowicz
authors: Kevin C
authors: KC
authors: Lord
authors: James A
authors: JA
authors: Stewart
authors: Mary J
authors: MJ
authors: Cismowski
authors: Kurt J
authors: KJ
authors: Varner
authors: Pamela A
authors: PA
authors: Lucchesi
mesh_terms: D000818:Animals; D001160:Arterioles / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D024042:Collagen Type I; D003331:Coronary Vessels / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D004548:Elasticity / Q000502:physiology*; D004549:Elastin / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D024042:Collagen Type I; D004549:Elastin