Since the early 1990s, several strains of genetically modified mice have been developed as models for experimental atherosclerosis. Among the available models, the apolipoprotein E-deficient (apoE-/-) mouse is of particular relevance because of its propensity to spontaneously develop hypercholesterolemia and atherosclerotic lesions that are similar to those found in humans, even when the mice are fed a chow diet. The main purpose of this review is to highlight the key achievements that have contributed to elucidating the mechanisms pertaining to vascular dysfunction in the apoE-/- mouse. First, we summarize lipoproteins and atherosclerosis phenotypes in the apoE-/- mouse, and then we briefly discuss controversial evidence relative to the influence of gender on the development of atherosclerosis in this murine model. Second, we discuss the main mechanisms underlying the endothelial dysfunction of conducting vessels and resistance vessels and examine how this vascular defect can be influenced by diet, aging and gender in the apoE-/- mouse.

Cardiovascular death is frequently associated with atherosclerosis, a chronic multifactorial disease and a leading cause of death worldwide. Genetically engineered mouse models have proven useful for the study of the mechanisms underlying cardiovascular diseases. The apolipoprotein E-deficient mouse has been the most widely used animal model of atherosclerosis because it rapidly develops severe hypercholesterolemia and spontaneous atherosclerotic lesions similar to those observed in humans. In this review, we provide an overview of the cardiac and vascular phenotypes and discuss the interplay among nitric oxide, reactive oxygen species, aging and diet in the impairment of cardiovascular function in this mouse model.

Abstract-It is known that the endothelial function is compromised in atherosclerosis and arterial hypertension and that angiotensin is an important factor contributing to both pathophysiologies. The aim of this study was to evaluate the vascular function in a hypercholesterolemia/atherosclerosis model, in the angiotensin II-dependent 2-kidney 1-clip (2K1C) hypertension model and when both conditions coexist. Eight-week-old apolipoprotein E knockout (apoE; nϭ20) and C57BL/6 (C57; nϭ20) mice underwent a 2K1C or sham operation and were studied 28 days later. Mean arterial pressure was higher in apoE-2K1C and C57-2K1C (126Ϯ3 and 128Ϯ3 mm Hg) when compared with the apoE-Sham and C57-Sham (103Ϯ2 and 104Ϯ2 mm Hg, respectively; PϽ0.05). The vascular reactivity to norepinephrine (NE; 10 Ϫ9to 2ϫ10 Ϫ3 mol/L), acetylcholine (ACh), and sodium nitroprusside (SNP; 10 Ϫ10 to 10 Ϫ3 mol/L) was evaluated in the mesenteric arteriolar bed through concentration-effect curves. NE caused vascular hyper-reactivity in apoE-Sham, apoE-2K1C, and C57-2K1C (maximal response 146Ϯ5, 144Ϯ5, and 159Ϯ4 mm Hg, respectively) compared with C57-Sham (122Ϯ7 mm Hg; PϽ0.05). The ACh-induced relaxation was smaller (PϽ0.05) in apoE-2K1C and C57-2K1C (maximal response 53Ϯ3% and 46Ϯ3%) than in apoE-Sham and C57-Sham mice (78Ϯ5% and 73Ϯ4%). SNP-induced vascular relaxation showed similar concentration-effect curves in all groups. We conclude that in C57-2K1C mice, the increased reactivity to NE and the decreased endothelium-dependent relaxation contribute to the maintenance of hypertension. The apoE mouse, at early stages of atherosclerosis, shows hyper-reactivity to NE but does not have endothelium dysfunction yet. However, the concurrence of both pathophysiologies does not result in additive effects on the vascular function. Key Words: atherosclerosis Ⅲ mice Ⅲ hypertension, renovascular Ⅲ apolipoproteins Ⅲ mesenteric arteries Ⅲ mice A therosclerosis and arterial hypertension are multifactorial diseases recognized as the main causes of acute cardiovascular events. These pathophysiologies are characterized by endothelial dysfunction, 1,2 and angiotensin II seems to be involved in both diseases. 3 Over the past decades, the availability of new investigative tools, including the homozygous apolipoprotein E knockout (apoE) mouse, has contributed to the understanding of the atherosclerotic process. ApoE is a constituent of VLDL synthesized by the liver and mediates high-affinity binding of apoEcontaining lipoprotein particles to LDL receptors, and thus is responsible for the cellular uptake of these particles. 4 Therefore, apoE mice develop marked hypercholesterolemia and spontaneous atherosclerosis. 4,5 In this experimental model, an endothelial dysfunction has been reported under a Western-type cholesterol-rich diet 6 -8 but not under a normal chow diet. 9 Arterial hypertension has also been associated with changes in endothelial function and in vascular smooth muscle cell reactivity to contractile agents. 10 In addition, arterial hypertension induced by endoge...

The gut microbiota, the ecosystem formed by a wide symbiotic community of nonpathogenic microorganisms that are present in the distal part of the human gut, plays a prominent role in the normal physiology of the organism. The gut microbiota’s imbalance, gut dysbiosis, is directly related to the origin of various processes of acute or chronic dysfunction in the host. Therefore, the ability to intervene in the gut microbiota is now emerging as a possible tactic for therapeutic intervention in various diseases. From this perspective, evidence is growing that a functional dietary intervention with probiotics, which maintain or restore beneficial bacteria of the digestive tract, represents a promising therapeutic strategy for interventions in cardiovascular diseases and also reduces the risk of their occurrence. In the present work, we review the importance of maintaining the balance of the intestinal microbiota to prevent or combat such processes as arterial hypertension or endothelial dysfunction, which underlie many cardiovascular disorders. We also review how the consumption of probiotics can improve autonomic control of cardiovascular function and provide beneficial effects in patients with heart failure. Among the known effects of probiotics is their ability to decrease the generation of reactive oxygen species and, therefore, reduce oxidative stress. Therefore, in this review, we specifically focus on this antioxidant capacity and its relationship with the beneficial cardiovascular effects described for probiotics.