Reciprocal Dynamics of Metabolism and mRNA Translation in Tumor Angiogenesis.

Angiogenesis, the process of formation of new blood vessels from pre-existing vasculature, is essential for tumor growth and metastasis. Anti-angiogenic treatment targeting vascular endothelial growth factor (VEGF) signaling is a powerful tool to combat tumor growth; however, anti-tumor angiogenesis therapy has shown limited efficacy, with survival benefits ranging from only a few weeks to months. Compensation by upregulation of complementary growth factors and switches to different modes of vascularization have made these types of therapies less effective.

The circadian protein BMAL1 supports endothelial cell cycle during angiogenesis.

Aims: The circadian clock is an internal biological timer that co-ordinates physiology and gene expression with the 24-h solar day. Circadian clock perturbations have been associated to vascular dysfunctions in mammals, and a function of the circadian clock in angiogenesis has been suggested. However, the functional role of the circadian clock in endothelial cells (ECs) and in the regulation of angiogenesis is widely unexplored.

How to Generate a Vascular-Labelled Transgenic Zebrafish Model to Study Tumor Angiogenesis and Extravasation.

The use of transgenic animals carrying exogenous DNA integrated in their genome is a routine in modern-day laboratories. Nowadays, the zebrafish system represents the most useful tool for transgenesis studies mainly due to easy accessibility and manipulation of the eggs, which are produced in high numbers and over a relatively short generation time. The zebrafish transgenic technology is very straightforward when coupled with angiogenesis studies allowing easy in vivo observation of the vertebrate embryonic vasculature.

Cancer-Induced Metabolic Rewiring of Tumor Endothelial Cells.

Cancer is a leading cause of death worldwide. If left untreated, tumors tend to grow and spread uncontrolled until the patient dies. To support this growth, cancer cells need large amounts of nutrients and growth factors that are supplied and distributed to the tumor tissue by the vascular system.

Aspartate metabolism in endothelial cells activates the mTORC1 pathway to initiate translation during angiogenesis.

Angiogenesis, the active formation of new blood vessels from pre-existing ones, is a complex and demanding biological process that plays an important role in physiological as well as pathological settings. Recent evidence supports cell metabolism as a critical regulator of angiogenesis. However, whether and how cell metabolism regulates endothelial growth factor receptor levels and nucleotide synthesis remains elusive.

Oxidative pentose phosphate pathway controls vascular mural cell coverage by regulating extracellular matrix composition.

Vascular mural cells (vMCs) play an essential role in the development and maturation of the vasculature by promoting vessel stabilization through their interactions with endothelial cells. Whether endothelial metabolism influences mural cell recruitment and differentiation is unknown. Here, we show that the oxidative pentose phosphate pathway (oxPPP) in endothelial cells is required for establishing vMC coverage of the dorsal aorta during early vertebrate development in zebrafish and mice.

LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion.

Dynamic modulation of endothelial cell-to-cell and cell-to-extracellular matrix (ECM) adhesion is essential for blood vessel patterning and functioning. Yet the molecular mechanisms involved in this process have not been completely deciphered. We identify the adhesion G protein-coupled receptor (ADGR) Latrophilin 2 (LPHN2) as a novel determinant of endothelial cell (EC) adhesion and barrier function.

Role of amino acid metabolism in angiogenesis.

The role of endothelial metabolism represents a crucial element governing the formation and the differentiation of blood vessels, termed angiogenesis. Besides glycolysis and fatty acid oxidation, endothelial cells rely on specific amino acids to proliferate, migrate, and survive. In this review we focus on the metabolism of those amino acids and the intermediates that hold an established function within angiogenesis and endothelial pathophysiology.

VLDL Induced Modulation of Nitric Oxide Signalling and Cell Redox Homeostasis in HUVEC.

High levels of circulating lipoprotein constitute a risk factor for cardiovascular diseases, and in this context, the specific role of the very-low-density lipoproteins (VLDL) is poorly understood. The response of human umbilical vein endothelial cells (HUVEC) to VLDL exposure was studied, especially focusing on the pathways involved in alteration of redox homeostasis and nitric oxide (NO) bioavailability. The results obtained by the analysis of the expression level of genes implicated in the NO metabolism and oxidative stress response indicated a strong activation of inducible NO synthase (iNOS) upon 24 h exposure to VLDL, particularly if these have been preventively oxidised.

Dermatan sulfate/chitosan polyelectrolyte complex with potential application in the treatment and diagnosis of vascular disease.

Cardiovascular disease is the largest single cause of morbid-mortality in the world. However, there is still no pharmaceutical treatment that directly targets the blood vessel wall instead of just controlling the risk factors. Here, we produced polyelectrolyte complexes (PECs) by a simple and reproducible polyelectrolyte complexation method between low molecular mass dermatan sulfate (polyanionic polysaccharide) and chitosan (polycationic polysaccharide), and evaluated the cellular uptake by vascular endothelial cells.

Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model.

Proteoglycan accumulation within the arterial intima has been implicated in atherosclerosis progression in humans. Nevertheless, hypercholesterolaemia is unable to induce intimal thickening and atheroma plaque development in rats. The study was performed to analyse proteoglycans modifications in rats fed with a high-cholesterol diet to understand whether vascular wall remodelling protects against lesions.

Decorin and biglycan expression: its relation with endothelial heterogeneity.

Decorin and biglycan proteoglycans play important roles in the organization of the extracellular matrix, and in the regulation of cell adhesion and migration. Given morphological and functional endothelial heterogeneity, information is needed regarding whether endothelial cells (ECs) from different vascular beds possess different profiles of proteoglycan constituents of the basement membranes. Here, we report that endothelia from different murine organs and EC lines derived thereof produce and secrete different patterns of proteoglycans.

Low-molecular-weight heparin inhibition in classical complement activation pathway during pregnancy.

Introduction: Low-molecular-weight heparin is used clinically for the prevention of pregnancy complications associated with prothrombotic disorders, particularly anti-phospholipid syndrome. Nevertheless, recent studies have suggested that heparin may exert direct effects on the placental trophoblast, independently of its anticoagulant activity. In addition, heparin prevents complement activation in vivo and protects mice from pregnancy complications.