Vascular Cell

[This corrects the article DOI: 10.1186/s13221-016-0038-2.].

Angiogenesis is a fundamental process during development and disease, and many details of the underlying molecular and cellular mechanisms are incompletely understood. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, has recently been identified as a regulator of Interleukin 1β dependent angiogenesis in vivo, and in vitro data suggest a role of MK2 for VEGF-dependent angiogenic processes in endothelial cells. We thus hypothesized that MK2 plays a role during physiological vascular development in vivo...

BACKGROUND: Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for advanced cell-based therapies. They are routinely obtained enzymatically from fat lipoaspirate (LP) as SVF, and may undergo prolonged ex vivo expansion, with significant senescence and decline in multipotency. Besides, these techniques have complex regulatory issues, thus incurring in the compelling requirements of GMP guidelines. Hence, availability of a minimally manipulated, autologous adipose tissue would have remarkable biomedical and clinical relevance...

BACKGROUND: Endothelial cells (EC) grown on collagen particles inhibit intimal hyperplasia in animal models when applied perivascularly, and this effect appears to be, at least in part, the result of EC-derived soluble factors that suppress local vascular inflammation. To elucidate the molecular basis of the therapeutic effects of EC grown on collagen particles, the anti-inflammatory activity of conditioned medium from these cells was characterized. METHODS: Human aortic EC (HAEC) and, for chromatin immunoprecipitation assays, human umbilical vein EC (HUVEC) were treated with tumor necrosis factor alpha (TNFα) in the presence of conditioned medium generated by HAEC grown on collagen particles (ECPCM), and the anti-inflammatory effects were evaluated by analysing the expression of the inflammation-related adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1)...

BACKGROUND: Biological evidence reported in the literature supports the role of CELSR1 as being essential for valvular function in murine lymphatics. Yet thus far, there have been no variants in CELSR1 associated with lymphatic dysfunction in humans. CASE PRESENTATION: In this report, a rare early inactivating mutation in CELSR1 is found to be causal for non-syndromic, lower extremity lymphedema in a family across three generations. Near-infrared fluorescence lymphatic imaging shows that instead of being propelled within the lumen of well-defined lymphatic vessels, lymph moved in regions of both legs in an unusual fashion and within sheet-like structures...

BACKGROUND: Angiogenesis is essential for uterine decidualization, the progesterone-mediated transformation of the uterus allowing embryo implantation and initiation of pregnancy. In the current study, we define the vasculature, expression of Notch proteins and Notch ligands, and Notch activity in both endothelial cells and vascular-associated mural cells of blood vessels in the pre-implantation endometrium and post-implantation decidua of the mouse uterus. METHODS: We used immunofluorescence to determine the expression of Notch in endothelial cells and mural cells by co-staining for the endothelial cell marker, CD31, the pan-mural cell marker, platelet-derived growth factor receptor beta (PDGFR-β), the pericyte markers, neural/glial antigen 2 (NG2) and desmin, or the smooth muscle cell marker, alpha smooth muscle actin (SMA)...

Vascular endothelial cells are subjected to hemodynamic forces such as mechanical stretch due to the pulsatile nature of blood flow. Mechanical stretch of different intensities is detected by mechanoreceptors on the cell surface which enables the conversion of external mechanical stimuli to biochemical signals in the cell, activating downstream signaling pathways. This activation may vary depending on whether the cell is exposed to physiological or pathological stretch intensities. Substantial stretch associated with normal physiological functioning is important in maintaining vascular homeostasis as it is involved in the regulation of cell structure, vascular angiogenesis, proliferation and control of vascular tone...

The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs) in the vessel wall to mechanical stress, in the form of circumferential and longitudinal stretch. Cyclic stretch evokes VSMC proliferation, apoptosis, phenotypic switching, migration, alignment, and vascular remodeling. Given that these responses have been observed in many cardiovascular diseases, a defined understanding of their underlying mechanisms may provide critical insight into the pathophysiology of cardiovascular derangements...

BACKGROUND: Multiple studies demonstrated pro-angiogenic effects of microRNA (miR)-27b. Its targets include Notch ligand Dll4, Sprouty (Spry)-2, PPARγ and Semaphorin (SEMA) 6A. miR-27 effects in the heart are context-dependent: although it is necessary for ventricular maturation, targeted overexpression in cardiomyocytes causes hypertrophy and dysfunction during development. Despite significant recent advances, therapeutic potential of miR-27b in cardiovascular disease and its effects in adult heart remain unexplored...

BACKGROUND: (-)-Solenopsin A is a piperidine alkaloid that is a component of the venom of the fire ant Solenopsis invicta. Previously, we have demonstrated that solenopsin exhibit anti-angiogenic activity and downregulate phosphoinositol-3 kinase (PI3K) in the p53 deficient renal cell carcinoma cell line 786-O. Solenopsin has structural similarities to ceramide, a major endogenous regulator of cell signaling and cancer therapy induced apoptosis. METHODS: Different analogs of solenopsin were synthesized in order to explore structure-activity relationships...

BACKGROUND: Vascular endothelial growth factor (VEGF) may play a role on the allograft remodelling following cardiac transplantation (CTx). We measured the circulating levels of VEGF-A165 concomitantly with the proinflammatory (Interleukin-8; IL-8), anti-inflammatory (IL-1 receptor antagonist; IL-1RA) and their release from neutrophils of CTx recipients. METHODS: Eighteen CTx recipients aged 49.6 ± 3.1 years, being transplanted for 145 ± 20 months were age-matched to 35 healthy control (HC) subjects...

BACKGROUND: Recent evidence suggests that a majority of RNAs in the genome do not code for proteins. They are located in the sense (S) or antisense (AS) orientation and, to date, the functional significance of these non-coding RNAs (ncRNAs) is poorly understood. Here, we examined the relationship between S and AS transcripts in the regulation of a key angiogenesis gene, Delta-like 4 (Dll4). METHODS: Rapid Amplification of cDNA Ends (RACE) method was used to identify natural antisense transcripts in the Dll4 gene locus in murine and human endothelial cells, referred to as Dll4 Anti-Sense (Dll4-AS)...

BACKGROUND: Angiogenesis plays a crucial role in development, wound healing as well as tumour growth and metastasis. Although the general implication of the cytoskeleton in angiogenesis has been partially unravelled, little is known about the specific role of actin isoforms in this process. Herein, we aimed at deciphering the function of γ-actin in angiogenesis. METHODS: Localization of β- and γ-actin in vascular endothelial cells was investigated by co-immunofluorescence staining using monoclonal antibodies, followed by the functional analysis of γ-actin using siRNA...

BACKGROUND: Therapeutic angiogenesis with vascular endothelial growth factor (VEGF), delivered either via recombinant protein infusion or via gene therapy, has shown promise in preclinical models of various diseases including myocardial infarction, renovascular disease, preeclampsia, and neurodegenerative disorders. However, dosing, duration of expression, and tissue specificity are challenges to VEGF gene therapy, and recombinant VEGF delivery suffers from extremely rapid plasma clearance, necessitating continuous infusion and/or direct injection at the site of interest...

BACKGROUND: The understanding of endothelial cell biology has been facilitated by the availability of primary endothelial cell cultures from a variety of sites and species; however, the isolation and maintenance of primary mouse aortic endothelial cells (MAECs) remain a formidable challenge. Culturing MAECs is difficult as they are prone to phenotypic drift during culture. Therefore, there is a need to have a dependable in vitro culture system, wherein the primary endothelial cells retain their properties and phenotypes...

Macrophages are highly plastic hematopoietic cells with diversified functions related to their anatomic location and differentiation states. A number of recent studies have examined the role of macrophages in solid organ transplantation. These studies show that macrophages can induce allograft injury but, conversely, can also promote tissue repair in ischemia-reperfusion injury and acute rejection. Therapeutic strategies that target macrophages to improve outcomes in solid organ transplant recipients are being examined in preclinical and clinical models...

BACKGROUND: Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a tubulin-binding drug and approved in many countries worldwide for treatment of certain patients with advanced breast cancer. Here we investigated antiproliferative and antiangiogenic effects of eribulin on vascular cells, human umbilical vein endothelial cells (HUVECs) and human brain vascular pericytes (HBVPs), in vitro in comparison with another tubulin-binding drug, paclitaxel...

A meeting report for Vascular Biology 2014, held in Monterey, California and organized by the North American Vascular Biology Organization (NAVBO).

BACKGROUND: The complex endocrine and exocrine functionality of the human pancreas depends on an efficient fluid transport through the blood and the lymphatic vascular systems. The lymphatic vasculature has key roles in the physiology of the pancreas and in regulating the immune response, both important for developing successful transplantation and cell-replacement therapies to treat diabetes. However, little is known about how the lymphatic and blood systems develop in humans. Here, we investigated the establishment of these two vascular systems in human pancreas organogenesis in order to understand neovascularization in the context of emerging regenerative therapies...

Chronic venous disease (CVD) has a range of clinical presentations, including tortuous, distended veins in lower extremities, increasing skin pigmentation, and in severe cases ulceration of the affected skin. Venous insufficiency, a precursor to CVD characterized by improper return of blood from the lower extremities to the heart, must be studied in its earliest stages at a time when preventative measures could be applied in man. This underscores the need for basic research into biomarkers and genetic predisposing factors affecting the progression of venous disease...