Regional variation in arterial stiffening and dysfunction in Western diet-induced obesity

Bender, Shawn B.; Castorena‐Gonzalez, Jorge A.; Garro, Mona; Reyes-Aldasoro, Constantino Carlos; Sowers, James R.; DeMarco, Vincent G.; Martinez‐Lemus, Luis A.

doi:10.1152/ajpheart.00155.2015

Cited by 55 publications

(63 citation statements)

References 51 publications

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“…These findings are of considerable translational importance given that obesity and insulin resistance are strongly associated with cardiovascular stiffness, especially in females. 16,25–27 …”

Section: Discussionmentioning

confidence: 99%

“…24 However, to date, the effect of exercise on endothelial stiffness associated with diet-induced obesity has not been examined. Herein, using a female mouse model of WD-induced obesity, insulin resistance and cardiovascular stiffness, 16,17,25–27 we tested the hypothesis that regular volitional exercise would reduce stiffness in the aortic endothelium, as assessed by AFM in aortic explants, as well as reduce in vivo aortic stiffness, as assessed by pulse wave velocity (PWV). Furthermore, we hypothesized that changes in aortic stiffness produced by exercise would be accompanied by a reduction in oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, we hypothesized that changes in aortic stiffness produced by exercise would be accompanied by a reduction in oxidative stress. Lastly, we reasoned that exercise-induced de-stiffening effects would be highly pronounced in the femoral artery, a muscular artery highly susceptible to WD-induced stiffness 27 and exposed to high blood flow and associated increased shear stress during exercise.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…The pattern of microvascular remodeling is also in contrast to that observed in larger conduit vessels. Here, obesity has been associated with increased vessel stiffness (6,52) and linked to the development of hypertension (62). While microvascular remodeling is not a prerequisite for hypertension (22), it does shape the nature of remodeling, as evidenced by the finding that microvascular stiffness was decreased in hypertensive, but not normotensive, obese humans (17,18).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide depletion contributes to microvascular remodeling in obesity

Candela

Velmurugan

White

2016

American Journal of Physiology-Heart and Circulatory Physiology

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Structural remodeling of the microvasculature occurs during obesity. Based on observations that impaired H2S signaling is associated with cardiovascular pathologies, the current study was designed to test the hypothesis that altered H2S homeostasis is involved in driving the remodeling process in a diet-induced mouse model of obesity. The structural and passive mechanical properties of mesenteric resistance arterioles isolated from 30-wk-old lean and obese mice were assessed using pressure myography, and vessel H2S levels were quantified using the H2S indicator sulfidefluor 7-AM. Remodeling gene expression was assessed using quantitative RT-PCR, and histological staining was used to quantify vessel collagen and elastin. Obesity was found to be associated with decreased vessel H2S concentration, inward hypertrophic remodeling, altered collagen-to-elastin ratio, and reduced vessel stiffness. In addition, mRNA levels of fibronectin, collagen types I and III, matrix metalloproteinases 2 and 9, and tissue inhibitor of metalloproteinase 1 were increased and elastin was decreased by obesity. Evidence that decreased H2S was responsible for the genetic changes was provided by experiments in which H2S levels were manipulated, either by inhibition of the H2S-generating enzyme cystathionine γ-lyase with dl-propargylglycine or by incubation with the H2S donor GYY4137. These data suggest that, during obesity, depletion of H2S is involved in orchestrating the genetic changes underpinning inward hypertrophic remodeling in the microvasculature.

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“…While clinical studies have shown that the stiffness of one vascular bed (e.g., human aorta) correlates with the stiffness of another (e.g., human carotid artery) (5), the work of Bender et al (3) suggests that this is not universally applicable. Perhaps the discrepancy lies in data generated in humans versus mouse, or perhaps it lies in the temporal or cumulative effect of exposure to a Western high-fat diet.…”

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Tissue-specific vascular remodeling and stiffness associated with metabolic diseases

Gooch

Trask

2015

American Journal of Physiology-Heart and Circulatory Physiology

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THE CONCEPT OF VASCULAR REMODELING was first mentioned in the late 1950s by Theodore Gillman (6, 7), who described variation in uterine artery remodeling among women of different ethnicities and ages. Early pioneering work by Baumbach and Heistad (2) further documented vascular remodeling and alterations in stiffness in cerebral resistance arterioles of hypertensive rats, providing seminal evidence that remodeling may be associated with altered vascular biomechanics. Their group described vascular remodeling as inward or outward and eutrophic, hypertrophic, or hypotrophic, depending on the amount of material comprising the vessel wall-a premise that provided the foundational definition of pathological vascular remodeling and mechanics that is still used today (10).The clinical implications of alterations in vessel size and mechanical stiffness are reflected in key studies that have demonstrated vascular stiffness-particularly increased carotidfemoral pulse wave velocity-as an independent predictor of cardiovascular disease and all-cause mortality, and alterations in vascular stiffness appear to be particularly accelerated in obese, diabetic, and metabolic syndrome (MetS) populations (9,13,16). A more recent study reported that local stiffness of the carotid and femoral artery, but not the brachial artery, is also associated with cardiovascular events and all-cause mortality (15), suggesting that arterial stiffness does not change uniformly across all vascular beds. Though under assessed experimentally, it is tempting to speculate that local alterations in arterial stiffness would predict localized vascular complications in a disease-specific manner. If so, estimates of coronary circulation stiffness would be especially important for predicting cardiovascular events. Unfortunately, there are no methods that directly measure arterial, including coronary, stiffness in vivo, and indirect measures (pulse wave velocity) are influenced by a variety of hemodynamic factors that are difficult to control (13).In the American Journal of Physiology-Heart and Circulatory Physiology, Bender and colleagues (3) explored whether alterations in the femoral artery might predict changes in the coronary artery. In a mouse model of Western diet-induced obesity, they demonstrated blood pressure-independent femoral artery endothelial dysfunction and stiffening in the absence of coronary artery endothelial dysfunction or stiffening. These results indicate that deleterious alterations in the femoral artery may not be predictive of coronary artery dysfunction or stiffness, at least in this mouse model of obesity. Their results further suggest that artery stiffening is not uniform but instead varies from tissue to tissue. This notion is also supported by our previous work with the type 2 diabetic db/db mouse model (8). Relative to control mice, diabetic mice exhibited increased stiffness in the aorta and femoral artery but decreased stiffness in the coronary microcirculation. We also demonstrated that stiffness was reduced in coronary resis...

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Regional variation in arterial stiffening and dysfunction in Western diet-induced obesity

Cited by 55 publications

References 51 publications

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

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

Hydrogen sulfide depletion contributes to microvascular remodeling in obesity

Tissue-specific vascular remodeling and stiffness associated with metabolic diseases

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