VEGF-C–dependent stimulation of lymphatic function ameliorates experimental inflammatory bowel disease

D’Alessio, Silvia; Correale, Carmen; Tacconi, Carlotta; Gandelli, Alessandro; Pietrogrande, Giovanni; Vetrano, Stefania; Genua, Marco; Arena, Vincenzo; Spinelli, Antonino; Peyrin–Biroulet, Laurent; Fiocchi, Claudio; Danese, Silvio

doi:10.1172/jci72189

Cited by 197 publications

(210 citation statements)

References 82 publications

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“…Recent studies in animals provide evidence that affecting lymphatic drainage by promoting the growth of lymphatic vessels can modulate inflammation 60, 61, 62, 63. Lymphatic vessel hyperplasia has been associated with hypercholesterolemia,42 but we show here that apoA‐I does not reduce vessel diameters.…”

Section: Discussioncontrasting

confidence: 43%

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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Section: Discussioncontrasting

confidence: 43%

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

Milasan

Jean

Dallaire

et al. 2017

JAHA

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“…( Figure 1 E) and their mean of fluorescence intensity (MFI) quantified, as recently described 22 . A lymphatic specific increase of VEGFR3 (Figure 1 The VEGFC/VEGFR3 pathway is actively involved in the metastatic process of a CRC orthotopic model…”

Section: Crcmentioning

confidence: 69%

Vascular Endothelial Growth Factor C Disrupts the Endothelial Lymphatic Barrier to Promote Colorectal Cancer Invasion

et al. 2015

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“…134 Production of GM-CSF and VEGF-C during inflammation may reprogramme the differentiation of monocytes into m that produce reparative mediators such as arginase, prostaglandins and IL-13. 200,201 Thus the overall role of the monocyte-m lineage in intestinal inflammation may reflect a balance between local pathogenic and regulatory mechanisms.…”

Section: Macrophages In Intestinal Inflammationmentioning

confidence: 99%

Diversity and functions of intestinal mononuclear phagocytes

et al. 2017

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VEGF-C–dependent stimulation of lymphatic function ameliorates experimental inflammatory bowel disease

Cited by 197 publications

References 82 publications

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

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

Vascular Endothelial Growth Factor C Disrupts the Endothelial Lymphatic Barrier to Promote Colorectal Cancer Invasion

Diversity and functions of intestinal mononuclear phagocytes

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