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01-11-2011 | Original Contribution

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

Authors: Paige S. Katz, Aaron J. Trask, Flavia M. Souza-Smith, Kirk R. Hutchinson, Maarten L. Galantowicz, Kevin C. Lord, James A. Stewart Jr., Mary J. Cismowski, Kurt J. Varner, Pamela A. Lucchesi

Published in: Basic Research in Cardiology | Issue 6/2011

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.

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Title: Coronary arterioles in type 2 diabetic (db/db) mice undergo a distinct pattern of remodeling associated with decreased vessel stiffness
Authors: Paige S. Katz
Aaron J. Trask
Flavia M. Souza-Smith
Kirk R. Hutchinson
Maarten L. Galantowicz
Kevin C. Lord
James A. Stewart Jr.
Mary J. Cismowski
Kurt J. Varner
Pamela A. Lucchesi
Publication date: 01-11-2011
Publisher: Springer-Verlag
Published in: Basic Research in Cardiology / Issue 6/2011
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-011-0201-0

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

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