1. Update June 2021 Francine Blei, MD
2. Matrix stiffness primes lymphatic tube formation directed by vascular endothelial growth factor‐C
3. Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function
4. Baranwal, G., et al. (2021). ``Dichotomous effects on Iymphatic transport with loss of caveolae in mice.'' Acta Physiol (Oxf): e13656. 2021/04/02 AIM: Fluid and macromolecule transport from the interstitium into and through Iymphatic vessels is necessary for tissue homeostasis. While Iymphatic capillary structure suggests that passive, paracellular transport would be the predominant route of macromolecule entry, active caveolae-mediated transcellular transport has been identified in Iymphatic endothelial cells (LECs) in vitro. Caveolae also mediate a wide array of endothelial cell processes, including nitric oxide regulation. Thus, how does the lack of caveolae impact ``lymphatic function''? METHODS: Various aspects of Iymphatic transport were measured in mice constitutively lacking caveolin-1 (``CavKO''), the protein required for caveolae formation in endothelial cells, and in mice with a LEC-specific Cav1 gene deletion (Lyve1-Cre x Cav1(flox/flox); ``LyCav'') and ex vivo
5. Becker, J., et al. (2021). ``Transcriptome Analysis of Hypoxic Lymphatic Endothelial Cells Indicates Their Potential to Contribute to Extracellular Matrix Rearrangement.'' Cells 10(5). 2021/05/01 Lymphedema (LE) affects millions of people worldwide. It is a chronic progressive disease with massive development of fibrosclerosis when untreated. There is no pharmacological treatment of Iymphedema. The disease is associated with swelling of the interstitium of the affected organ, mostly arm or leg, impressive development of adipose tissue, fibrosis and sclerosis with accumulation of huge amounts of collagen, and Papillomatosis cutis. Malnutrition and reduced oxygenation of the affected tissues is a hallmark of Iymphedema. Here, we investigated if the hypoxia of Iymphatic endothelial cells (LECs) might contribute to fibrosis. We applied RNASeq and qPCR to study the concordant changes of the exome of three human foreskin-derived LEC isolates after 4 days of hypoxia (1% O2) vs. normoxia (21% O2). Of the approximately 16,000 genes expressed in LECs, 162 (1%) were up- or downregulated by hypoxia. Of these, 21 genes have important functions in the production or modification of the extracellular matrix (ECM). In addition to the down-regulation of elastin, we found up-regulation of druggable enzymes and regulators such as the long non-coding RNA H19, inter-alpha-trypsin inhibitor heavy chain family member 5 (ITIH5), Iysyl-oxidase (LOX), prolyl 4-hydroxylase subunit alpha 1 (P4HA1), procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), and others that are discussed in the paper. Initial Iymphatics do not produce a continuous basement membrane; however, our study shows that hypoxic LECs have an unexpectedly high ability to alter the ECM.