Aging associated with mild dyslipidemia reveals that COX-2 preserves dilation despite endothelial dysfunction

Gendron, Marie-Ève; Thorin‐Trescases, Nathalie; Villeneuve, Louis; Thorin, Éric

doi:10.1152/ajpheart.00551.2006

Cited by 36 publications

(60 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An increased cholesterol level was reported, but this dyslipidemia seemed to have no deleterious outcome in terms of cardiovascular aging, as shown by vascular and cardiac Doppler-echography results. Although the consequences of this dyslipidemia in young mice have not been evaluated with arterial reactivity experiments, our results are in line with those of a previous study showing that dyslipidemia had no effect on the endothelial function in 3-mo-old mice (16). The pathways involved in the dilation of mouse arteries evolve during maturation and aging, demonstrating that the endothelial biology is dynamic with time and most likely results from time-dependent injuries and repairs (15).…”

Section: Discussionsupporting

confidence: 90%

High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age

Bédarida

Baron

Vessières

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Cottart C, Nivet-Antoine V. High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age. Am J Physiol Heart Circ Physiol 307: H649 -H657, 2014. First published July 11, 2014; doi:10.1152/ajpheart.00291.2014.-High-protein-lowcarbohydrate (HP-LC) diets have become widespread. Yet their deleterious consequences, especially on glucose metabolism and arteries, have already been underlined. Our previous study (2) has already shown glucose intolerance with major arterial dysfunction in very old mice subjected to an HP-LC diet. The hypothesis of this work was that this diet had an age-dependent deleterious metabolic and cardiovascular outcome. Two groups of mice, young and adult (3 and 6 mo old), were subjected for 12 wk to a standard or to an HP-LC diet. Glucose and lipid metabolism was studied. The cardiovascular system was explored from the functional stage with Doppler-echography to the molecular stage (arterial reactivity, mRNA, immunohistochemistry). Young mice did not exhibit any significant metabolic modification, whereas adult mice presented marked glucose intolerance associated with an increase in resistin and triglyceride levels. These metabolic disturbances were responsible for cardiovascular damages only in adult mice, with decreased aortic distensibility and left ventricle dysfunction. These seemed to be the consequence of arterial dysfunctions. Mesenteric arteries were the worst affected with a major oxidative stress, whereas aorta function seemed to be maintained with an appreciable role of cyclooxygenase-2 to preserve endothelial function. This study highlights for the first time the age-dependent deleterious effects of an HP-LC diet on metabolism, with glucose intolerance and lipid disorders and vascular (especially microvessels) and cardiac functions. This work shows that HP-LC lead to equivalent cardiovascular alterations, as observed in very old age, and underlines the danger of such diet. cardiovascular disease; glucose intolerance; high-protein-low-carbohydrate diet CHANGE IN WESTERN lifestyle, with an increasingly fat-rich diet and decreased physical activity, has led to increased overweight and obesity prevalence. Type 2 diabetes and metabolic syndrome have now become endemic (40), leading to increased cardiovascular morbidity and mortality (3). This trend does not concern only mature adults, but also teenagers and young adults, in whom the prevalence of diabetes and being overweight has been increasing (29). Some nutritional strategies have become more and more prevalent, such as highprotein-low-carbohydrate (HP-LC) diets (8). However, their deleterious outcomes on glucose metabolism and arteries have already been underlined (7, 12). Aortas as well as microvessels such as mesenteric arteries are altered with aging. Oxidative stress is one of the most important factors implied in these alterations. The reactive oxygen species (ROS) producers, such as NADPH oxidase, seem to be implied, leading to the vascular inflammation (30,35). Moreover, the deficiency of...

show abstract

Section: Discussionsupporting

confidence: 90%

High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age

Bédarida

Baron

Vessières

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…MAPK : mitogen activated protein kinase ; ATM : ataxia telangiectasia muté ; H2AX : histone de type H2AX ; pRb : protéine rétinoblastome phosphorylée. [32]. Nous avons démontré que l'endothélium est un système dynamique continuellement exposé à des dommages et à des réparations [32,33].…”

Section: Vieillissement Endothélial Dans Un Environnement Pro-oxydantunclassified

“…[32]. Nous avons démontré que l'endothélium est un système dynamique continuellement exposé à des dommages et à des réparations [32,33]. Nous avons ainsi observé des changements dans la contribution des différents facteurs vasoactifs endothéliaux au cours de la maturation (phase normale du développement de l'endothélium, qui est suivie de la dysfonction lors du vieillissement).…”

Section: Vieillissement Endothélial Dans Un Environnement Pro-oxydantunclassified

“…Nous avons ainsi observé des changements dans la contribution des différents facteurs vasoactifs endothéliaux au cours de la maturation (phase normale du développement de l'endothélium, qui est suivie de la dysfonction lors du vieillissement). Ces changements permettent de maintenir une fonction endothéliale, mais ils sont néanmoins prédictifs d'une future dysfonction [32][33][34]. Ainsi, l'endothélium artériel rénal d'une souris adulte âgée de 6 mois sécrète plus de thromboxane A 2 (TXA 2 ) que celui d'une souris jeune de 3 mois [34].…”

Section: Vieillissement Endothélial Dans Un Environnement Pro-oxydantunclassified

“…Cette production de thromboxane est induite par les ROS puisqu'elle est réversible par un traitement anti-oxydant tel que la NAC [34]. Chez une souris âgée (12 à 20 mois) et dyslipi démique, la dysfonction endothéliale dans une artère de conductance (artère rénale) provient d'une perte de NO partiellement compensée par une augmentation de production de prostacycline dilatatrice [32], alors qu'elle provient plutôt d'un déclin précoce d'EDHF dans une artère de résistance (artère gracilis) [33]. Nous avons également observé que dans les artères cérébrales de souris athérosclérotiques (souris C57Bl6…”

Section: Vieillissement Endothélial Dans Un Environnement Pro-oxydantunclassified

See 2 more Smart Citations

Âge et stress oxydant

et al. 2010

Self Cite

View full text Add to dashboard Cite

High glucose increases expression of cyclooxygenase‐2, increases oxidative stress and decreases the generation of nitric oxide in mouse microvessel endothelial cells

Aljofan

Ding

2009

Journal Cellular Physiology

View full text Add to dashboard Cite

Hyperglycaemia is a key factor that contributes to the development of diabetes-related microvascular disease. Both cyclooxygenase I and cyclooxygenase II are expressed in endothelial cells and play key roles in the regulation of cardiovascular function. In the current study we tested the hypothesis that hyperglycaemia-induced increased expression of cyclooxygenase II is a contributing factor both to the increased oxidative stress and to the reduction in the generation of nitric oxide in microvessel endothelial cells following their exposure to high glucose. We demonstrated that the exposure of mouse microvascular endothelial cells to high glucose for 3 days decreased the generation of nitric oxide and enhanced production of superoxide. Western blots illustrated that exposure to high glucose also increased endothelial nitric oxide synthase and cyclooxygenase II protein expression levels and decreased the dimer/monomer ratio of endothelial nitric oxide synthase protein. All the changes induced by the high glucose culture media could be reversed by either the cyclooxygenase II inhibitor CAY10404, the non-selective cyclooxygenase inhibitor indomethacin or the protein kinase C inhibitor chelerythrine, but not solely by preincubation with the antioxidant and putative NADPH oxidase inhibitor, apocynin. Our data indicate that high glucose induced oxidative stress is linked to an increase in the expression of cyclooxygenase II and a reduced generation of nitric oxide that is associated with an uncoupled endothelial nitric oxide synthase, possibly due to decreased dimer/monomer ratio.

show abstract

Aging associated with mild dyslipidemia reveals that COX-2 preserves dilation despite endothelial dysfunction

Cited by 36 publications

References 36 publications

High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age

High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age

Âge et stress oxydant

High glucose increases expression of cyclooxygenase‐2, increases oxidative stress and decreases the generation of nitric oxide in mouse microvessel endothelial cells

Contact Info

Product

Resources

About