Abstract
The vascular dysfunction is the primary event in the occurrence of cardio-vascular risk, and no treatment exists until now. We tested for the first time the hypothesis that chitin-glucan (CG) - an insoluble fibre with prebiotic properties- and polyphenol-rich pomegranate peel extract (PPE) can improve endothelial and inflammatory disorders in a mouse model of cardiovascular disease (CVD), namely by modulating the gut microbiota. Male Apolipoprotein E knock-out (ApoE−/−) mice fed a high fat (HF) diet developed a significant endothelial dysfunction attested by atherosclerotic plaques and increasing abundance of caveolin-1 in aorta. The supplementation with CG + PPE in the HF diet reduced inflammatory markers both in the liver and in the visceral adipose tissue together with a reduction of hepatic triglycerides. In addition, it increased the activating form of endothelial NO-synthase in mesenteric arteries and the heme-nitrosylated haemoglobin (Hb-NO) blood levels as compared with HF fed ApoE−/− mice, suggesting a higher capacity of mesenteric arteries to produce nitric oxide (NO). This study allows to pinpoint gut bacteria, namely Lactobacillus and Alistipes, that could be implicated in the management of endothelial and inflammatory dysfunctions associated with CVD, and to unravel the role of nutrition in the modulation of those bacteria.
Highlights
Despite the enormous progress made in the diagnosis and treatment of cardiovascular diseases (CVDs) over the last twenty years, CVDs remain the leading cause of disability and death in Western countries[1]
This effect was not statistically significant due to large variability, CG with or without pomegranate peel extract (PPE) decreased the level of ALAT in the serum (ALAT activity expressed in U/L: 16.4 ± 6.6, 16.6 ± 5.2, 6.7 ± 1.2, 8.8 ± 1.9 for CT, high fat (HF), CG and CG + PPE groups, respectively)
We demonstrated that n-3 PUFA depletion for 12 weeks could accelerate the process of endothelium dysfunction in young Apolipoprotein E (ApoE)−/− mice prone to develop atherosclerosis[19]
Summary
Despite the enormous progress made in the diagnosis and treatment of cardiovascular diseases (CVDs) over the last twenty years, CVDs remain the leading cause of disability and death in Western countries[1]. Endothelial dysfunction is an early key marker of CVDs reflecting the integrated effects of risk factors on the vascular system[3]. Endothelium-dependent relaxation is reduced in response to acetylcholine in 13-months-old ApoE−/− mice compared to wild-type mice[6] This is not observed in youngest mice, suggesting that vascular disorders occurring in ApoE deficiency depend on age. We and others have demonstrated that dietary fibre supplementation modulates the composition of the gut microbiota, and eventually improves host physiology[13,15,16]. This is the case for inulin-type fructans (ITF), which are classified as prebiotics.
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