Leukocyte Trafficking via Lymphatic Vessels in Atherosclerosis

Yeo, Kim Pin; Lim, Hwee Ying; Angeli, Véronique

doi:10.3390/cells10061344

Cited by 10 publications

(9 citation statements)

References 128 publications

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“…We identified distinct fibroblast subsets as the main cellular source of VEGF-C production. It has been shown that lymphatic vessels mainly exist within the adventitial vessel wall, especially when atherosclerotic plaques possess a high expression level of VEGF-C. 36 We observed an intrinsic colocalization of fibrosis and lymphatic vessels within vascular allografts, supporting the notion that local fibroblasts release VEGF-C to directly stimulate lymphangiogenesis in situ.…”

Section: Discussionsupporting

confidence: 82%

The Effect of Lymphangiogenesis in Transplant Arteriosclerosis

et al. 2023

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BACKGROUND: Transplant arteriosclerosis is a major complication in long-term survivors of heart transplantation. Increased lymph flow from donor heart to host lymph nodes has been reported to play a role in transplant arteriosclerosis, but how lymphangiogenesis affects this process is unknown. METHODS: Vascular allografts were transplanted among various combinations of mice, including wild-type, Lyve1 -CreER T2 ;R26-tdTomato, CAG-Cre-tdTomato, severe combined immune deficiency, Ccr2 KO , Foxn1 KO , and lghm / lghd KO mice. Whole-mount staining and 3-dimensional reconstruction identified lymphatic vessels within the grafted arteries. Lineage tracing strategies delineated the cellular origin of lymphatic endothelial cells. Adeno-associated viral vectors and a selective inhibitor were used to regulate lymphangiogenesis. RESULTS: Lymphangiogenesis within allograft vessels began at the anastomotic sites and extended from preexisting lymphatic vessels in the host. Tertiary lymphatic organs were identified in transplanted arteries at the anastomotic site and lymphatic vessels expressing CCL21 (chemokine [C-C motif] ligand 21) were associated with these immune structures. Fibroblasts in the vascular allografts released VEGF-C (vascular endothelial growth factor C), which stimulated lymphangiogenesis into the grafts. Inhibition of VEGF-C signaling inhibited lymphangiogenesis, neointima formation, and adventitial fibrosis of vascular allografts. These studies identified VEGF-C released from fibroblasts as a signal stimulating lymphangiogenesis extending from the host into the vascular allografts. CONCLUSIONS: Formation of lymphatic vessels plays a key role in the immune response to vascular transplantation. The inhibition of lymphangiogenesis may be a novel approach to prevent transplant arteriosclerosis.

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Section: Discussionsupporting

confidence: 82%

The Effect of Lymphangiogenesis in Transplant Arteriosclerosis

et al. 2023

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“…VV is a specialized microvasculature that transports nutrients and oxygen to the adventitia and two-thirds of the media layer within the aortic wall. Adventitial lymphatic vessels modulate inflammation of the aortic wall by draining interstitial fluid and trafficking the immune cells through the aortic wall ( Kutkut et al, 2015 ; Yeo et al, 2021 ). Perivascular innervation in the adventitia modulates functions of VSMCs and ECs to regulate vascular tone ( Nava and Llorens, 2019 ).…”

Section: Anatomy Of Aortamentioning

confidence: 99%

Extracellular Matrix in Aging Aorta

Mammoto

Matus

Mammoto

2022

Front. Cell Dev. Biol.

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The aging population is booming all over the world and arterial aging causes various age-associated pathologies such as cardiovascular diseases (CVDs). The aorta is the largest elastic artery, and transforms pulsatile flow generated by the left ventricle into steady flow to maintain circulation in distal tissues and organs. Age-associated structural and functional changes in the aortic wall such as dilation, tortuousness, stiffening and losing elasticity hamper stable peripheral circulation, lead to tissue and organ dysfunctions in aged people. The extracellular matrix (ECM) is a three-dimensional network of macromolecules produced by resident cells. The composition and organization of key ECM components determine the structure-function relationships of the aorta and therefore maintaining their homeostasis is critical for a healthy performance. Age-associated remodeling of the ECM structural components, including fragmentation of elastic fibers and excessive deposition and crosslinking of collagens, is a hallmark of aging and leads to functional stiffening of the aorta. In this mini review, we discuss age-associated alterations of the ECM in the aortic wall and shed light on how understanding the mechanisms of aortic aging can lead to the development of efficient strategy for aortic pathologies and CVDs.

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“…Leukocyte egression from the plaques plays a critical role in atherosclerosis. 46,47 Thus, we quantified the ability of neutrophils, isolated from either healthy controls or patients, to migrate across a monolayer of LECs in the presence or absence of a chemoattractant (IL-8: 5 ng/ml) (schematic illustration, Figure 5A). There was no difference in spontaneous transmigration of neutrophils from controls or patients (Figure 5B).…”

Section: Lipoxin B 4 Treatment Enhances Lymphatic Transmigration Of N...mentioning

confidence: 99%