The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

Effects of adenosine on lymphangiogenesis.

BACKGROUND: The lymphatic system controls tissue homeostasis by draining protein-rich lymph to the vascular system. Lymphangiogenesis, the formation of lymphatic vessels, is a normal event in childhood but promotes tumor spread and metastasis during adulthood. Blocking lymphangiogenesis may therefore be of therapeutic interest. Production of adenosine is enhanced in the tumor environment and contributes to tumor progression through stimulation of angiogenesis. In this study, we determined whether adenosine affects lymphangiogenesis. METHODS: Lymphatic endothelial cells (HMVEC-dLy) were cultured in presence of adenosine and their proliferation, migration and tube formation was assessed. Gelatin sponges embedded with the stable analogue of adenosine 2-chloro adenosine were implanted in mice ear and lymphangiogenesis was quantified. Mice were intravenously injected with adenoviruses containing expression vector for 5'-endonucleotidase, which plays a major role in the formation of adenosine. RESULTS: In vitro, we observed that adenosine decreased the proliferation of lymphatic endothelial cells, their migration and tube formation. However, in vivo, gelatin sponges containing 2-chloro adenosine and implanted in mice ear displayed an elevated level of lymphangiogenesis (2.5-fold, p<0.001). Adenovirus-mediated over-expression of cytosolic 5'-nucleotidase IA stimulated lymphangiogenesis and the recruitment of macrophages in mouse liver. Proliferation of lymphatic endothelial cells was enhanced (2-fold, p<0.001) when incubated in the presence of conditioned medium from murine macrophages. CONCLUSION: We have shown that adenosine stimulates lymphangiogenesis in vivo, presumably through a macrophage-mediated mechanism. This observation suggests that blockade of adenosine receptors may help in anti-cancer therapies

Zebrafish models of dyslipidemia: relevance to atherosclerosis and angiogenesis

Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably similar. Zebrafish express all major nuclear receptors, lipid transporters, apolipoproteins and enzymes involved in lipoprotein metabolism. Unlike mice, zebrafish express cetp and the Cetp activity is detected in zebrafish plasma. Feeding zebrafish a high cholesterol diet, without any genetic intervention, results in significant hypercholesterolemia and robust lipoprotein oxidation, making zebrafish an attractive animal model to study mechanisms relevant to early development of human atherosclerosis. These studies are facilitated by the optical transparency of zebrafish larvae and the availability of transgenic zebrafish expressing fluorescent proteins in endothelial cells and macrophages. Thus, vascular processes can be monitored in live animals. In this review article we discuss recent advances in using dyslipidemic zebrafish in atherosclerosis-related studies. We also summarize recent work connecting lipid metabolism with regulation of angiogenesis, the work that considerably benefited from using the zebrafish model. These studies uncovered the role of aibp, abca1, abcg1, mtp, apoB and apoC2 in regulation of angiogenesis in zebrafish and paved the way for future studies in mammals, which may suggest new therapeutic approaches to modulation of excessive or diminished angiogenesis contributing to the pathogenesis of human disease

Parental vitamin deficiency affects the embryonic gene expression of immune-, lipid transport- and apolipoprotein genes

World Health Organization is concerned for parental vitamin deficiency and its effect on offspring health. This study examines the effect of a marginally dietary-induced parental one carbon (1-C) micronutrient deficiency on embryonic gene expression using zebrafish. Metabolic profiling revealed a reduced 1-C cycle efficiency in F(0) generation. Parental deficiency reduced the fecundity and a total of 364 genes were differentially expressed in the F(1) embryos. The upregulated genes (53%) in the deficient group were enriched in biological processes such as immune response and blood coagulation. Several genes encoding enzymes essential for the 1-C cycle and for lipid transport (especially apolipoproteins) were aberrantly expressed. We show that a parental diet deficient in micronutrients disturbs the expression in descendant embryos of genes associated with overall health, and result in inherited aberrations in the 1-C cycle and lipid metabolism. This emphasises the importance of parental micronutrient status for the health of the offspring

ApoB versus non-HDL-cholesterol: Diagnosis and cardiovascular risk management

Item does not contain fulltextAbstract The most recent guidelines released by the EAS/ESC and the Canadian Cardiovascular Society (CCS) retain low-density lipoprotein cholesterol (LDL-C) as the primary measure of the atherogenic risk of the apolipoprotein B (apoB) lipoproteins and the primary target of LDL-C lowering therapy. Both organizations endorse non-high-density lipoprotein cholesterol (non-HDL-C) and apoB as "alternate/secondary" targets, but neither group offers evidence supporting the continued preference of LDL-C as the primary target over non-HDL-C and apoB. Further, both suggest that non-HDL-C and apoB more or less measure the same thing and, therefore, are essentially interchangeable. But what is the evidence that LDL-C should remain the primary target, and are apoB and non-HDL-C mirror images of one another? Furthermore, are estimation of risk and establishment of treatment targets the only relevant issues, or is diagnosis also an essential objective? These are the questions this article will address. Our principal objectives are: (1) to clarify the differences between LDL-C, non-HDL-C, and apoB and to distinguish what they measure; (2) to summarize the evidence relating to LDL-C, non-HDL-C, and apoB as predictors of cardiovascular risk and as targets for treatment; and (3) to demonstrate that diagnosis of atherogenic dyslipoproteinemias should be a fundamental clinical priority

Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply

Lipoprotein lipase (LPL) hydrolyzes triglycerides to supply free fatty acids (FFAs) to muscle for energy and adipocytes for storage. Here, the authors demonstrate that Lpl and its product, the FFA docosahexaenoic acid (DHA) are required for haematopoietic stem progenitor cell expansion during zebrafish embryogenesis