Search results for "ANGIOGENESIS"
showing 10 items of 552 documents
Endothelial Leptin Receptor Deletion Promotes Cardiac Autophagy and Angiogenesis Following Pressure Overload by Suppressing Akt/mTOR Signaling.
2019
Background: Cardiac remodeling is modulated by overnutrition or starvation. The adipokine leptin mediates energy balance between adipose tissue and brain. Leptin and its receptors are expressed in the heart. Methods and Results: To examine the importance of endothelial leptin signaling in cardiac hypertrophy, transverse aortic constriction was used in mice with inducible endothelium-specific deletion of leptin receptors (End.LepR-KO) or littermate controls (End.LepR-WT). End.LepR-KO was associated with improved left ventricular function (fractional shortening, 28.4% versus 18.8%; P =0.0114), reduced left ventricular dilation (end-systolic inner left ventricular diameter, 3.59 versus 4.08 m…
Novel 3-Azaindolyl-4-arylmaleimides Exhibiting Potent Antiangiogenic Efficacy, Protein Kinase Inhibition, and Antiproliferative Activity
2012
Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.
The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development
2014
Low density lipoprotein receptor-related protein 1 (LRP1) is indispensable for embryonic development. Comparing different genetically engineered mouse models, we found that expression of Lrp1 is essential in the embryo proper. Loss of LRP1 leads to lethal vascular defects with lack of proper investment with mural cells of both large and small vessels. We further demonstrate that LRP1 modulates Gi-dependent sphingosine-1-phosphate (S1P) signaling and integrates S1P and PDGF-BB signaling pathways, which are both crucial for mural cell recruitment, via its intracellular domain. Loss of LRP1 leads to a lack of S1P-dependent inhibition of RAC1 and loss of constraint of PDGF-BB-induced cell migra…
Central role of IL-6 and MMP-1 for cross talk between human intestinal mast cells and human intestinal fibroblasts.
2012
Mast cells (MC) are key effector cells in allergic reactions but also involved in host defence, tissue remodeling, angiogenesis, and fibrogenesis. Here, we show that human intestinal fibroblasts (FB) suppress apoptosis in human intestinal MC dependent on IL-6. Intestinal FB produced IL-6 upon direct stimulation by intestinal MC in co-culture or by MC mediators such as TNF-α, IL-1β, tryptase or histamine. MC incubated with IL-6 survived for up to 3 weeks similar to MC co-cultured with FB and MC survival could be blocked by neutralizing anti-IL-6 Abs. Moreover, FB stimulated by MC mediators upregulated their expression of matrix metalloproteinase-1 (MMP-1), a key fibrolytic enzyme. Noteworthy…
Stimulation of Wound Revascularization by Adenosine Receptor Activation
2010
Adenosine is an endogenous mediator implicated in wound healing. The exact mechanisms and receptors involved are still under evaluation. We have observed that topical application of a selective adenosine A2A receptor agonist promotes wound healing in experimental animals, both healthy and with impaired healing. Histological analysis revealed that adenosine promoted granulation tissue formation, with increased cellularity, matrix deposition, and vessel density. Adenosine may exert effects on many different cell types that finally result in promotion of angiogenesis and, furthermore, homing of endothelial precursor cells into sites of injury. We will review the effect of adenosine receptor ac…
Cyclooxygenase inhibitors – current status and future prospects
2001
Prostaglandins are formed from arachidonic acid by the action of cyclooxygenase and subsequent downstream synthetases. Two closely related forms of the cyclooxygenase have been identified which are now known as COX-1 and COX-2. Both isoenzymes transform arachidonic acid to prostaglandins, but differ in their distribution and their physiological roles. Meanwhile, the responsible genes and their regulation have been clarified. COX-1, the pre-dominantly constitutive form of the enzyme, is expressed throughout the body and performs a number of homeostatic functions such as maintaining normal gastric mucosa and influencing renal blood flow and platelet aggregation. In contrast, the inducible for…
A recommended practical approach to the management of target therapy and angiogenesis inhibitors cardiotoxicity: an opinion paper of the working grou…
2016
The US National Cancer Institute estimates that cardiotoxicity (CTX) from target therapy refers mostly to four groups of drugs: epidermal growth factor receptor 2 inhibitors, angiogenic inhibitors, directed Abelson murine leukemia viral oncogene homolog inhibitors, and proteasome inhibitors. The main cardiotoxic side-effects related to antiepidermal growth factor receptor 2 therapy are left ventricular systolic dysfunction and heart failure. Angiogenesis inhibitors are associated with hypertension, left ventricular dysfunction/heart failure, myocardial ischemia, QT prolongation, and thrombosis. Moreover, other agents may be related to CTX induced by treatment. In this study, we review the g…
The transmembrane receptor Uncoordinated5 (Unc5) is essential for heart lumen formation in Drosophila melanogaster
2011
AbstractTransport of liquids or gases in biological tubes is fundamental for many physiological processes. Our knowledge on how tubular organs are formed during organogenesis and tissue remodeling has increased dramatically during the last decade. Studies on different animal systems have helped to unravel some of the molecular mechanisms underlying tubulogenesis. Tube architecture varies dramatically in different organs and different species, ranging from tubes formed by several cells constituting the cross section, tubes formed by single cells wrapping an internal luminal space or tubes that are formed within a cell. Some tubes display branching whereas others remain linear without interse…
Rapid vascularization of starchâ poly(caprolactone) in vivo by outgrowth endothelial cells in co-culture with primary osteoblasts
2011
The successful integration of in vitro-generated tissues is dependent on adequate vascularization in vivo. Human outgrowth endothelial cells (OECs) isolated from the mononuclear cell fraction of peripheral blood represent a potent population of circulating endothelial progenitors that could provide a cell source for rapid anastomosis and scaffold vascularization. Our previous work with these cells in co-culture with primary human osteoblasts has demonstrated their potential to form perfused vascular structures within a starch–poly(caprolactone) biomaterial in vivo. In the present study, we demonstrate the ability of OECs to form perfused vascular structures as early as 48 h following subcut…
Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.
2015
Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean m…