Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

Gil‐Ortega, Marta; Martín-Ramos, Miriam; Arribas, Silvia M.; González, M. C.; Aránguez, Isabel; Ruiz‐Gayo, Mariano; Somoza, Beatriz; Fernández-Alfonso, Marı́a S.

doi:10.1016/j.vph.2015.05.012

Cited by 24 publications

(41 citation statements)

References 61 publications

(94 reference statements)

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“…Furthermore, we report for the first time that regular exercise increased the number of fenestrae and area occupied by fenestrae in the internal elastic lamina of the femoral artery. Our novel finding that regular exercise increased the number of fenestrae in the internal elastic lamina of femoral arteries is of relevance in light of prior findings by our group and others demonstrating that high-fat diet decreases the number of fenestrae in the internal elastic lamina of femoral 27 and mesenteric 57,58 arteries of mice. These changes in fenestration of the internal elastic lamina may be associated with changes in the elastic properties of the vessels as well as with the communication between endothelial and vascular smooth muscle cells within the vascular wall.…”

Section: Discussionsupporting

confidence: 71%

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: Discussionsupporting

confidence: 71%

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

et al. 2016

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“…Obese children exhibit worse profiles of carotid intima-media thickness, PWV and flow-mediated dilatation, reflecting vascular damage (31,32) , and several clinical and experimental obesity-related studies have found that oxidative stress is significantly associated with changes in these vascular parameters (33)(34)(35)(36) . Interestingly, in our sample, we found an unexpected positive correlation between PWV and TAS values.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function

et al. 2016

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Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H 2 O 2 ), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H 2 O 2 , myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H 2 O 2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H 2 O 2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend = 0·003). We conclude that oxidant status and NO are increased Abbreviations: ABPM, ambulatory blood pressure monitoring; eGFR, estimated glomerular filtration rate; HOMA-IR, homoeostasis model assessment of insulin resistance; hs-CRP, high-sensitivity C-reactive protein; MAP, mean arterial pressure; MPO, myeloperoxidase; NO, nitric oxide; NOS, NO synthase; P-Isop, plasma isoprostanes; P-NOx, plasma nitrates and nitrites; PWV, pulse wave velocity; ROS, reactive oxygen species; TAS, total antioxidant status; U-H 2 O 2 , urinary hydrogen peroxide; U-Isop, urinary isoprostanes; U-NOx, urinary nitrates and nitrites; WHtR, waist:height ratio.

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“…Paradoxically the reduction in elastin content was also associated with a significant reduction in the area occupied by fenestrae in the IEL and a specific reduction in the number of fenestra in the IEL of arteries from offspring fed a HFD that were obtained from hyperleptinemic dams. Consumption of a HFD has been previously shown to be associated with significant reduction in the fenestrae of vessels [ 43 , 62 ]. Calculation of the elastic modulus normalized as a function of the percolation of the internal elastic lamina and its fenestrae suggests that a reduction in the number and size of fenestrae may participate in augmenting the stiffness of mesenteric arteries in animals fed a HFD [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Maternal Hyperleptinemia Is Associated with Male Offspring’s Altered Vascular Function and Structure in Mice

et al. 2016

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Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Leprdb/+ dams were compared to genotype matched offspring of WT-control dams. Vascular function was assessed in male offspring at 6, and at 31 weeks of age after half the offspring had been fed a high fat, high sucrose diet (HFD) for 6 weeks. Blood pressure was increased by HFD but not affected by maternal hyperleptinemia. On a standard diet, offspring of hyperleptinemic dams had outwardly remodeled mesenteric arteries and an enhanced vasodilatory response to insulin. In offspring of WT but not Leprdb/+ dams, HFD induced vessel hypertrophy and enhanced vasodilatory responses to acetylcholine, while HFD reduced insulin responsiveness in offspring of hyperleptinemic dams. Offspring of hyperleptinemic dams had stiffer arteries regardless of diet. Therefore, while maternal hyperleptinemia was largely beneficial to offspring vascular health under a standard diet, it had detrimental effects in offspring fed HFD. These results suggest that circulating maternal leptin concentrations may interact with other factors in the pre- and post -natal environments to contribute to altered vascular function in offspring of diabetic pregnancies.

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Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

Cited by 24 publications

References 61 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

Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function

Maternal Hyperleptinemia Is Associated with Male Offspring’s Altered Vascular Function and Structure in Mice

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