Regular Exercise Reduces Endothelial Cortical Stiffness in Western Diet–Fed Female Mice

Abstract

We recently showed that Western diet (WD)-induced obesity and insulin resistance promotes endothelial cortical stiffness in young female mice. Herein, we tested the hypothesis that regular aerobic exercise would attenuate the development of endothelial and whole artery stiffness in female WD-fed mice. Four-week old C57BL/6 mice were randomized into sedentary (i.e., caged confined, n=6) or regular exercise (i.e., access to running wheels, n=7) conditions for 16 weeks. Exercise training improved glucose tolerance in the absence of changes in body weight and body composition. Compared to sedentary mice, exercise-trained mice exhibited reduced endothelial cortical stiffness in aortic explants (sedentary: 11.9±1.7 kPa vs. exercise: 5.5±1.0 kPa; p<0.05), as assessed by atomic force microscopy. This effect of exercise was not accompanied by changes in aortic pulse wave velocity (p>0.05), an in vivo measure of aortic stiffness. In comparison, exercise reduced femoral artery stiffness in isolated pressurized arteries and led to an increase in femoral internal artery diameter and wall cross-sectional area (p<0.05), indicative of outward hypertrophic remodeling. These effects of exercise were associated with an increase in femoral artery elastin content and increased number of fenestrae in the internal elastic lamina (p<0.05). Collectively, these data demonstrate for the first time that the aortic endothelium is highly plastic and thus amenable to reductions in stiffness with regular aerobic exercise in the absence of changes in in vivo whole aortic stiffness. Comparatively, the same level of exercise caused de-stiffening effects in peripheral muscular arteries such as the femoral artery that perfuse the working limbs.

Exercise during pregnancy mitigates the adverse effects of maternal obesity on adult male offspring vascular function and alters one‐carbon metabolism

“…Exercise is accepted as a nonpharmacological means of improving vascular endothelial function and reducing atherosclerosis (Guizoni et al, 2016;Laufs et al, 2004;Napoli et al, 2004;Padilla et al, 2016). For example, forced exercise (swimming) reduced aortic lesion area (Napoli et al, 2004) and treadmill training improved thoracic aorta endothelial-dependent vasodilatation (Guizoni et al, 2016) in low density lipoprotein receptor-deficient mice.…”

“…For example, forced exercise (swimming) reduced aortic lesion area (Napoli et al, 2004) and treadmill training improved thoracic aorta endothelial-dependent vasodilatation (Guizoni et al, 2016) in low density lipoprotein receptor-deficient mice. Futhermore, female C57BL/6 mice fed a western diet with access to a running wheel (voluntary exercise) had lower endothelial cortical stiffness in thoracic aorta explants and lower femoral artery stiffness compared to sedentary mice (Padilla et al, 2016).…”

Mechanisms and Subclinical Consequences of Aortic Stiffness

“…In contrast, wheel running reversed femoral artery stiffness and this was associated with increases in elastin and number of fenestrae in the internal elastic laminae. 47 These data suggest that the improvements in the endothelial cell surface stiffness and fenestrae with exercise may precede changes in aortic stiffness, or alternatively, that exercise training was not long enough or stiffness adaptations are specific to the arteries perfusing the exercising muscle in this model.…”

Beneficial Effects of Exercise on Subendothelial Matrix Stiffness Are Short-Lived

“…Increased collagen is a major cause of increased arterial stiffness associated with advanced age [4,8,15]. While previous studies focus on changes in total vessel or medial collagen [4,8,15,16], here, we focus on the collagen in the subendothelial matrix. Intimal collagen content was assessed based on the PSR polarization signal assessed using structured illumination microscopy ( Fig.…”

“…We also examined possible causes for the observed changes in the arterial stiffness changes. While it is known that age-induced whole vessel [23] or diet-induced medial [16] collagen content is decreased following exercise, here we examined the role of collagen in the intimal layer alone. Different collagen types are present in the intima layer, such as type IV collagen and collagen I and III fibers [24][25][26].…”