Lymphatic Network in Atherosclerosis: the Underestimated Path

Milasan, Andreea; Ledoux, Jonathan; Martel, Catherine

doi:10.4155/fso.15.61

Cited by 25 publications

(22 citation statements)

References 68 publications

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“…In order to confirm our finding in the artery wall, we investigated the presence of initial lymphatics in the adventitia of the aortic sinus ( Fig. 2e ), a blood vessel layer where LVs have been consistently observed 26 . Once again, no difference was seen at any age when looking at the morphology or density of Lyve-1 + vessels ( Fig.…”

Section: Resultssupporting

confidence: 60%

“…It has been reported that without a functional lymphatic network, cholesterol cannot leave the artery wall and might potentially aggravate the disease. Accordingly, it is now suggested that cholesterol leaves tissues and reaches the bloodstream by first entering lymphatic vessels (LVs), putting forward a new integrated model for mRCT 24 25 26 . The blood vasculature and the lymphatic system are parallel and interdependent networks 27 .…”

mentioning

confidence: 99%

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Effects of LDL Receptor Modulation on Lymphatic Function

Milasan

Dallaire

Mayer

et al. 2016

Sci Rep

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Atherosclerosis is driven by the accumulation of immune cells and cholesterol in the arterial wall. Although recent studies have shown that lymphatic vessels play an important role in macrophage reverse cholesterol transport, the specific underlying mechanisms of this physiological feature remain unknown. In the current report, we sought to better characterize the lymphatic dysfunction that is associated with atherosclerosis by studying the physiological and temporal origins of this impairment. First, we assessed that athero-protected Pcsk9−/− mice exhibited improved collecting lymphatic vessel function throughout age when compared to WT mice for up to six months, while displaying enhanced expression of LDLR on lymphatic endothelial cells. Lymphatic dysfunction was present before the atherosclerotic lesion formation in a mouse model that is predisposed to develop atherosclerosis (Ldlr−/−; hApoB100+/+). This dysfunction was presumably associated with a defect in the collecting lymphatic vessels in a non-specific cholesterol- but LDLR-dependent manner. Treatment with a selective VEGFR-3 agonist rescued this impairment observed early in the onset of this arterial disease. We suggest that LDLR modulation is associated with early atherosclerosis-related lymphatic dysfunction, and bring forth a pleiotropic role for PCSK9 in lymphatic function. Our study unveils new potential therapeutic targets for the prevention and treatment of atherosclerosis.

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Section: Resultssupporting

confidence: 60%

mentioning

confidence: 99%

Effects of LDL Receptor Modulation on Lymphatic Function

Milasan

Dallaire

Mayer

et al. 2016

Sci Rep

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“…[17][18][19] The concept that lymphatic vessels could influence atherogenesis and lipoprotein transport has first been brought forward several decades ago. [20][21][22] However, we had to wait until recently to directly associate the lymphatic system with atherosclerosis, [23][24][25][26][27] a disease driven by the accumulation of cholesterol in the artery wall, primarily by low-density lipoprotein, leading to increased plaque buildup. 28 It has been described that without a functional lymphatic network, cholesterol excreted from plaque macrophages cannot be properly conducted out of the artery wall, and thus cannot be evacuated.…”

mentioning

confidence: 99%

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Milasan

Jean

Dallaire

et al. 2017

JAHA

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BackgroundSubcutaneously injected lipid‐free apoA‐I (apolipoprotein A‐I) reduces accumulation of lipid and immune cells within the aortic root of hypercholesterolemic mice without increasing high‐density lipoprotein–cholesterol concentrations. Lymphatic vessels are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and particular attention has been brought to the role of the collecting lymphatic vessels in early atherosclerosis‐related lymphatic dysfunction. In the present study, we address whether and how preservation of collecting lymphatic function contributes to the protective effect of apoA‐I.Methods and ResultsAtherosclerotic Ldlr −/− mice treated with low‐dose lipid‐free apoA‐I showed enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr −/− mice when compared with albumin‐control mice. Treatment of human lymphatic endothelial cells with apoA‐I increased the adhesion of human platelets on lymphatic endothelial cells, in a bridge‐like manner, a mechanism that could strengthen endothelial cell–cell junctions and limit atherosclerosis‐associated collecting lymphatic vessel dysfunction. Experiments performed with blood platelets isolated from apoA‐I‐treated Ldlr −/− mice revealed that apoA‐I decreased ex vivo platelet aggregation. This suggests that in vivo apoA‐I treatment limits platelet thrombotic potential in blood while maintaining the platelet activity needed to sustain adequate lymphatic function.ConclusionsAltogether, we bring forward a new pleiotropic role for apoA‐I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.

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“…Moreover, most studies have focused on the detection of milk microRNAs in the blood circulation. As previously suggested Dever et al, 2015;Tome-Carneiro et al, 2018) milk microRNAs could be directly used by the digestive tract cells (Tome-Carneiro et al, 2018), reach the colon to regulate microbiota (Liu et al, 2016;Yu et al, 2019) or end up circulating in lymphatic vessels that contain numerous EVs and transport molecules originating from food (Milasan et al, 2016;Milasan, Ledoux, & Martel, 2015).…”

Section: Limitations and Future Perspectivesmentioning

confidence: 97%

Milk MicroRNAs in Health and Disease

Benmoussa

Provost

2019

Comp Rev Food Sci Food Safe

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MicroRNAs are small noncoding RNAs responsible for regulating 40% to 60% of gene expression at the posttranscriptional level. The discovery of circulating microRNAs in several biological fluids opened the path for their study as biomarkers and long‐range cell‐to‐cell communication mediators. Their transfer between individuals in the case of blood transfusion, for example, and their high enrichment in milk have sparked the interest for microRNA transfer through diet, especially from mothers to infants during breastfeeding. The extension of such paradigm led to the study of milk microRNAs in the case of cow or goat milk consumption in adults. Here we provide a comprehensive critical review of the key findings surrounding milk microRNAs in human, cow, and goat milk among other species. We discuss the data on their biological properties, their use as disease biomarkers, their transfer between individuals or species, and their putative or verified functions in health and disease of infants and adult consumers. This work is based on all the literature available and integrates all the results, theories, debates, and validation studies available so far on milk microRNAs and related areas of investigations. We critically discuss the limitations and outline future aspects and avenues to explore in this rapidly growing field of research that could impact public health through infant milk formulations or new therapies. We hope that this comprehensive review of the literature will provide insight for all teams investigating milk RNAs’ biological activities and help ensure the quality of future reports.

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Lymphatic Network in Atherosclerosis: the Underestimated Path

Cited by 25 publications

References 68 publications

Effects of LDL Receptor Modulation on Lymphatic Function

Effects of LDL Receptor Modulation on Lymphatic Function

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Milk MicroRNAs in Health and Disease

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