I nverse Relationship Between Vascular Size and Stiffness in the Presence and Absence of Diabetes

Abstract

Vascular stiffness is increasingly garnering more interest in part as a result of data over the recent past demonstrating that macrovascular stiffness is associated with increased cardiovascular disease and mortality. Our past data has demonstrated vascular bed-specific differences in stiffness among the diabetic aorta, mesenteric, and coronary beds. Recent pilot data from our laboratory suggested that macrovessels appeared to have reduced stiffness when compared to microvessels from the same animal; however, there is a paucity of data in the literature to support this notion in a well-controlled study. The current study sought to test the hypothesis that macrovessels are less stiff compared to microvessels under normal and diabetic conditions. Large mesenteric arteries (1°/2° branches; average internal diameters: ~325-380 µm), small mesenteric arteries (3°/4° branches; average internal diameters: ~200-208 µm), and small mesenteric microvessels (5°/6° branches; average internal diameters: ~121-132 µm) were dissected from the same 16 week-old normal Db/db and type 2 diabetic db/db mice and mounted on a pressure myograph for passive structural and biomechanical measurements. In normal mice, incremental elastic modulus (Einc between 75-125 mmHg), a measure of vascular stiffness, of large arteries averaged 3.29x105 ± 1.00x105 dyn/cm2, which was significantly lower than small artery (7.47x106 ± 0.72x106 dyn/cm2, p<0.01) and microvessel Einc (9.95x106 ± 1.68x106 dyn/cm2, p<0.001). Similarly in db/db mice, Einc of large arteries averaged 9.35x105 ± 3.95x105 dyn/cm2, which was significantly lower than small artery (7.80x106 ± 1.10x106 dyn/cm2, p<0.01) and microvessel Einc (9.21x106 ± 1.76x106 dyn/cm2, p<0.05). The clinically-relevant beta stiffness index followed a similar pattern in vessels isolated from both normal and diabetic mice. Pearson correlation analyses revealed significant inverse correlations between mesenteric internal diameter and Einc (Normal: r=-0.71, p<0.001; db/db: r=-0.63, p<0.05). A similar association was found between internal diameter and beta stiffness index (Normal: r=-0.74, p<0.001; db/db: r=-0.57, p<0.05). These data show that, in a well-controlled animal model and within the same vascular bed, as vessel size increases, stiffness decreases regardless of glycemic status. The reasons for this finding are currently unclear, but they could involve differences in the composition and biomechanics of the extracellular matrix, vascular cell stiffness, and/or linkage of the ECM and cell cytoskeleton through integrins.