Endent vascular relaxations, decreased endothelium-independent vascular relaxations, and/or increased vasoconstrictions > 자유게시판

Endent vascular relaxations, decreased endothelium-independent vascular relaxations, and/or increased vasoconstrictions [57-60].Endothelial Function and Dysfunction in the ApoE-/- MouseThe influence of diet, age and gender on endothelial function of large arteriesOne hallmark of atherosclerosis is vascular dysfunction, which is observed mainly in large vessels and has generally been defined by a decreased in 5,6-Dichloro-1H-indole endothelium-dependent vasodilation that is generally considered to precede the development of atherosclerosis and to predispose humans to the development of structural vascular changes [61]. However, this general concept is not fully supported by studies in the murine model of spontaneous hypercholesterolemia and atherosclerosis. Indeed, aortic rings isolated from young (6-18-week-old) male and female apoE-/- mice fed a standard chow diet (hypercholesterolemia only) exhibit a preserved endothelial NOdependent relaxation response to ACh when compared with wild-type control mice [12,62,63]. Similar results have been observed in aortas from adult (20-35-weekold) male [64] and female [4,65] apoE-/- mice. In contrast, in aged apoE-/- mice (50-70-week-old) that exhibit both hypercholesterolemia and established atherosclerosis, an endothelial dysfunction, as demonstrated by a significantly blunted aorta relaxation response to ACh, has been observed [62,66,67]. When apoE-/- mice are fed a Western-type diet to accelerate and aggravate hypercholesterolemia and atherosclerosis, the vasodilation response to ACh in the aortas [23,64,65] and PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/13867361 carotid arteries [23] of 20-30-week-old males is normal; however, studies have shown a significant impairment of the vasodilation response to ACh in 14-15-week-old male [22,65,68-76] and female [4,19,77] mice. Crauwels et al. [66] demonstrated that in aged (72-week-old) apoE -/mice, the aortic endothelial dysfunction is a focal and not a systemic PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/10572343 hypercholesterolemia-dependent defect, i.e., it is strictly associated with plaque formation. Overall, the above findings (see diagram in Figure 4) suggest that endothelial function in the aortas of apoE -/- mice isnormal at the early stages of the pathology and the impairment of endothelial NO-mediated dilation occurs at a later stage, mainly in aged animals and when mice are fed an atherogenic Western-type diet, which aggravates hypercholesterolemia and atherosclerosis. Recent evidence suggests that gender plays an important role in endothelial dysfunction in the large vessels of apoE-/- mice. Indeed, atherosclerosis in apoE-/- mice 2-Chloro-3-methoxyaniline was reduced and the endothelial dysfunction of aortic rings was attenuated following ovariectomy and was aggravated by treatment with 17-b-estradiol at doses that were near physiological levels [37]. Hence, the apoE-/- mouse, in addition to being a model for human atherosclerosis, appears to be a suitable experimental model for studying the detrimental effects of 17-b-estradiol on endothelial dysfunction [37]. Despite a growing body of evidence suggesting that gender influences atherosclerosis in apoE-/- mice [30-38], few studies have investigated the differences in endothelial function between males and females. More interesting is that ijms17122034 a large number of publications have not revealed the gender of the mice used in the studies. In humans, there is a general concept that endothelial dysfunction precedes the development of atherosclerosis [41]. Moreover, there is evidence that the impaired endothelial NO-dependent relaxation response to.