http://www.vascularcell.com The most accessed research articles published by Vascular Cell 2012-04-30T00:00:00Z Functional signaling between neural stem/progenitor cells (NSPCs) and brain endothelial cells (ECs) is essential to the coordination of organized responses during initial embryonic development and also during tissue repair, which occurs following brain injury. In this study, we investigated the molecular mechanisms underlying this functional signaling, using primary mouse brain ECs and NSPCs from embryonic mouse brain. EC/NSPC co-culture experiments have revealed that neural progenitors secrete factors supporting angiogenesis, which induce noticeable changes in endothelial morphology. We demonstrate that NSPCs influence the expression of mTOR and TGF-β signaling pathway components implicated in the regulation of angiogenesis. Endothelial morphogenesis, an essential component of vascular development, is a complex process involving gene activation and the upregulation of specific cell signaling pathways. Recently identified small molecules, called microRNAs (miRNAs), regulate the expression of genes and proteins in many tissues, including brain and vasculature. We found that NSPCs induced considerable changes in the expression of at least 24 miRNAs and 13 genes in ECs. Three NSPC-regulated EC miRNAs were identified as the potential primary mediators of this NSPC/EC interaction. We found that the specific inhibition, or overexpression, of miRNAs miR-155, miR-100, and miR-let-7i subsequently altered the expression of major components of the mTOR, TGF-β and IGF-1R signaling pathways in ECs. Overexpression of these miRNAs in ECs suppressed, while inhibition activated, the in vitro formation of capillary-like structures, a process representative of EC morphogenesis. In addition, we demonstrate that inhibition of FGF, VEGF, and TGF-β receptor signaling abolished NSPC-promoted changes in the endothelial miRNA profiles. Our findings demonstrate that NSPCs induce changes in the miRNA expression of ECs, which are capable of activating angiogenesis by modulating distinct cell signaling pathways. http://www.vascularcell.com/content/3/1/25 Tamara Roitbak Olga Bragina Jamie Padilla Gavin Pickett Vascular Cell 2011, null:25 2011-11-09T00:00:00Z doi:10.1186/2045-824X-3-25 /content/figures/2045-824X-3-25-toc.gif Vascular Cell 2045-824X ${item.volume} 25 2011-11-09T00:00:00Z XML Natural health products (NHP) which include minerals, vitamins and herbal remedies are notgenerally considered by medical practitioners as conventional medicines and as such are notfrequently prescribed by health centre's as either main-line or supplemental treatments. In thefield of cardiovascular medicine, studies have shown that typically, less than half of patientssuffering from coronary syndromes chose to take any form of NHP supplement and theseproducts are rarely recommended by their medical practitioner. Vascular/endothelial celldamage is a key instigator of coronary arterial plaque development which often culminates inthrombosis and myocardial infarction (MI). Current treatment for patients known to be at riskof primary or secondary (MI) includes lipid lowering statins, anti-clotting agents (e.g. tissueplasminogen activator; tPA) and drugs for stabilization of blood pressure such as betablockers. However, evidence has been building which suggests that components of at least several NHP (e.g. aged garlic extract (AGExt), resveratrol and green tea extracts (GTE)) may have significant vascular protective effects through reduction of oxidative stress, lowering of blood pressure, reduction in platelet aggregation, vasodilation and inhibition of abnormal angiogenesis. Therefore, in this review we will discuss in detail the potential of these substances (chosen on the basis of their potency and complimentarity) as anti-atherosclerotic agents and the justification for their consideration as main-line additional supplements or prescriptions. http://www.vascularcell.com/content/4/1/9 mark slevin Nessar Ahmed Quiyu Wang Garry Mcdowell Lina Badimon Vascular Cell 2012, null:9 2012-04-30T00:00:00Z doi:10.1186/2045-824X-4-9 /content/figures/2045-824X-4-9-toc.gif Vascular Cell 2045-824X ${item.volume} 9 2012-04-30T00:00:00Z PDF Anti-angiogenesis agents and the identification of cancer stem-like cells (CSC) are opening new avenues for targeted cancer therapy. Recent evidence indicates that angiogenesis regulatory pathways and developmental pathways that control CSC fate are intimately connected, and that endothelial cells are a key component of the CSC niche. Numerous anti-angiogenic therapies developed so far target the VEGF pathway. However, VEGF-targeted therapy is hindered by clinical resistance and side effects, and new approaches are needed. One such approach may be direct targeting of tumor endothelial cell fate determination. Interfering with tumor endothelial cells growth and survival could inhibit not only angiogenesis but also the self-replication of CSC, which relies on signals from surrounding endothelial cells in the tumor microenvironment. The Notch pathway is central to controlling cell fate both during angiogenesis and in CSC from several tumors. A number of investigational Notch inhibitors are being developed. Understanding how Notch interacts with other factors that control endothelial cell functions and angiogenesis in cancers could pave the way to innovative therapeutic strategies that simultaneously target angiogenesis and CSC. http://www.vascularcell.com/content/4/1/7 Jian-Wei Gu Paola Rizzo Antonio Pannuti Todd Golde Barbara Osborne Lucio Miele Vascular Cell 2012, null:7 2012-04-09T00:00:00Z doi:10.1186/2045-824X-4-7 /content/figures/2045-824X-4-7-toc.gif Vascular Cell 2045-824X ${item.volume} 7 2012-04-09T00:00:00Z XML This Commentary emphasizes the fundamental contribution of William Harvey to the discovery of the circulation of the blood and his scientific and experimental approach to this matter. http://www.jangiogenesis.com/content/1/1/3 Domenico Ribatti Vascular Cell 2009, null:3 2009-09-21T00:00:00Z doi:10.1186/2040-2384-1-3 /content/figures/2040-2384-1-3-toc.gif Vascular Cell 2045-824X ${item.volume} 3 2009-09-21T00:00:00Z XML Angiogenesis is disregulated in many diseased states, most notably in cancer. An emerging strategy for the development of therapies targeting tumor-associated angiogenesis is to harness the potential of nanotechnology to improve the pharmacology of chemotherapeutics, including anti-angiogenic agents. Nanoparticles confer several advantages over that of free drugs, including their capability to carry high payloads of therapeutic agents, confer increased half-life and reduced toxicity to the drugs, and provide means for selective targeting of the tumor tissue and vasculature. The plethora of nanovectors available, in addition to the various methods available to combine them with anti-angiogenic drugs, allows researchers to fine-tune the pharmacological profile of the drugs ad infinitum. Use of nanovectors has also opened up novel avenues for non-invasive imaging of tumor angiogenesis. Herein, we review the types of nanovector and therapeutic/diagnostic agent combinations used in targeting tumor angiogenesis. http://www.vascularcell.com/content/3/1/3 Deboshri Banerjee Rania Harfouche Shiladitya Sengupta Vascular Cell 2011, null:3 2011-01-31T00:00:00Z doi:10.1186/2045-824X-3-3 /content/figures/2045-824X-3-3-toc.gif Vascular Cell 2045-824X ${item.volume} 3 2011-01-31T00:00:00Z XML Angiogenesis is the growth of new blood vessels and is a key process which occurs during both physiological and pathological disease processes. Knowledge of the mechanisms through which this process is initiated and maintained will have a significant impact on the treatment of these diseases. Pathological angiogenesis occurs in major diseases such as cancer, diabetic retinopathies, age-related macular degeneration and atherosclerosis. In other diseases such as stroke and myocardial infarction, insufficient or improper angiogenesis results in tissue loss and ultimately higher morbidity and mortality. http://www.jangiogenesis.com/content/1/1/1 Mark Slevin Yihai Cao Jan Kitajewski Vascular Cell 2009, null:1 2009-09-21T00:00:00Z doi:10.1186/2040-2384-1-1 /content/figures/2040-2384-1-1-toc.gif Vascular Cell 2045-824X ${item.volume} 1 2009-09-21T00:00:00Z XML Heparin is an anticoagulant agent known to have diverse effects on angiogenesis with some reports suggesting that it can induce angiogenesis while a few have indicated of its inhibitory property. Cancer patients treated for venous thromboembolism with low molecular heparin had a better survival than the unfractionated heparin (UFH). Heparin is known to interact with various angiogenic growth factors based on its sulfation modifications within the glycosaminoglycan chains Therefore it is important to study the mechanism of action of heparin of different molecular weight to understand its angiogenic property. In this concern we examined the angiogenic response of higher molecular weight Heparin (15 kDa) of different concentrations using late CAM assay. Growth of blood vessels in terms of their length and size was measured and thickness of the CAM was calculated morphometrically. The observed increase in the thickness of the CAM is suggestive of the formation of capillary like structures at the treated region. Analysis of the diffusion pattern showed internalized action of heparin that could affect gene expression leading to proliferation of endothelial cells. Angiogenesis refers to formation of new blood vessels from the existing ones and occurrence of new blood vessels at the treated area strongly confirms that heparin of 15 kDa molecular weight has the ability to induce angiogenesis on CAM vascular bed in a dose dependent manner. The results demonstrate the affinity of heparin to induce angiogenesis and provide a novel mechanism by which heparin could be used in therapeutics such as in wound healing process. http://www.vascularcell.com/content/4/1/8 Reji Bhuvanendran Rema Karthick Rajendran Malathi Ragunathan Vascular Cell 2012, null:8 2012-04-18T00:00:00Z doi:10.1186/2045-824X-4-8 /content/figures/2045-824X-4-8-toc.gif Vascular Cell 2045-824X ${item.volume} 8 2012-04-18T00:00:00Z PDF Background: Much of our current understanding of microvascular permeability is based on the findings of classic experimental studies of blood capillary permeability to various-sized lipid-insoluble endogenous and non-endogenous macromolecules. According to the classic small pore theory of microvascular permeability, which was formulated on the basis of the findings of studies on the transcapillary flow rates of various-sized systemically or regionally perfused endogenous macromolecules, transcapillary exchange across the capillary wall takes place through a single population of small pores that are approximately 6 nm in diameter; whereas, according to the dual pore theory of microvascular permeability, which was formulated on the basis of the findings of studies on the accumulation of various-sized systemically or regionally perfused non-endogenous macromolecules in the locoregional tissue lymphatic drainages, transcapillary exchange across the capillary wall also takes place through a separate population of large pores, or capillary leaks, that are between 24 and 60 nm in diameter. The classification of blood capillary types on the basis of differences in the physiologic upper limits of pore size to transvascular flow highlights the differences in the transcapillary exchange routes for the transvascular transport of endogenous and non-endogenous macromolecules across the capillary walls of different blood capillary types. Methods: The findings and published data of studies on capillary wall ultrastructure and capillary microvascular permeability to lipid-insoluble endogenous and non-endogenous molecules from the 1950s to date were reviewed. In this study, the blood capillary types in different tissues and organs were classified on the basis of the physiologic upper limits of pore size to the transvascular flow of lipid-insoluble molecules. Blood capillaries were classified as non-sinusoidal or sinusoidal on the basis of capillary wall basement membrane layer continuity or lack thereof. Non-sinusoidal blood capillaries were further sub-classified as non-fenestrated or fenestrated based on the absence or presence of endothelial cells with fenestrations. The sinusoidal blood capillaries of the liver, myeloid (red) bone marrow, and spleen were sub-classified as reticuloendothelial or non-reticuloendothelial based on the phago-endocytic capacity of the endothelial cells. Results: The physiologic upper limit of pore size for transvascular flow across capillary walls of non-sinusoidal non-fenestrated blood capillaries is less than 1 nm for those with interendothelial cell clefts lined with zona occludens junctions (i.e. brain and spinal cord), and approximately 5 nm for those with clefts lined with macula occludens junctions (i.e. skeletal muscle). The physiologic upper limit of pore size for transvascular flow across the capillary walls of non-sinusoidal fenestrated blood capillaries with diaphragmed fenestrae ranges between 6 and 12 nm (i.e. exocrine and endocrine glands); whereas, the physiologic upper limit of pore size for transvascular flow across the capillary walls of non-sinusoidal fenestrated capillaries with open 'non-diaphragmed' fenestrae is approximately 15 nm (kidney glomerulus). In the case of the sinusoidal reticuloendothelial blood capillaries of myeloid bone marrow, the transvascular transport of non-endogenous macromolecules larger than 5 nm into the bone marrow interstitial space takes place via reticuloendothelial cell-mediated phago-endocytosis and transvascular release, which is the case for systemic bone marrow imaging agents as large as 60 nm in diameter. Conclusions: The physiologic upper limit of pore size in the capillary walls of most non-sinusoidal blood capillaries to the transcapillary passage of lipid-insoluble endogenous and non-endogenous macromolecules ranges between 5 and 12 nm. Therefore, macromolecules larger than the physiologic upper limits of pore size in the non-sinusoidal blood capillary types generally do not accumulate within the respective tissue interstitial spaces and their lymphatic drainages. In the case of reticuloendothelial sinusoidal blood capillaries of myeloid bone marrow, however, non-endogenous macromolecules as large as 60 nm in diameter can distribute into the bone marrow interstitial space via the phago-endocytic route, and then subsequently accumulate in the locoregional lymphatic drainages of tissues following absorption into the lymphatic drainage of periosteal fibrous tissues, which is the lymphatic drainage of myeloid bone marrow. When the ultrastructural basis for transcapillary exchange across the capillary walls of different capillary types is viewed in this light, it becomes evident that the physiologic evidence for the existence of aqueous large pores ranging between 24 and 60 nm in diameter in the capillary walls of blood capillaries, is circumstantial, at best. http://www.jangiogenesis.com/content/2/1/14 Hemant Sarin Vascular Cell 2010, null:14 2010-08-11T00:00:00Z doi:10.1186/2040-2384-2-14 /content/figures/2040-2384-2-14-toc.gif Vascular Cell 2045-824X ${item.volume} 14 2010-08-11T00:00:00Z XML Plaque angiogenesis may have an important role in the development of atherosclerosis. Vasa vasorum angiogenesis and medial infiltration provides nutrients to the developing and expanding intima and therefore, may prevent cellular death and contribute to plaque growth and stabilization in early lesions. However in more advanced plaques, inflammatory cell infiltration, and concomitant production of numerous pro-angiogenic cytokines may be responsible for induction of uncontrolled neointimal microvessel proliferation resulting in production of immature and fragile neovessels similar to that seen in tumour development. These could contribute to development of an unstable haemorrhagic rupture-prone environment. Increasing evidence has suggested that the expression of intimal neovessels is directly related to the stage of plaque development, the risk of plaque rupture, and subsequently, the presence of symptomatic disease, the timing of ischemic neurological events and myocardial/cerebral infarction. Despite this, there is conflicting evidence regarding the causal relationship between neovessel expression and plaque thrombosis with some in vivo experimental models suggesting the contrary and as yet, few direct mediators of angiogenesis have been identified and associated with plaque instability in vivo.In recent years, an increasing number of angiogenic therapeutic targets have been proposed in order to facilitate modulation of neovascularization and its consequences in diseases such as cancer and macular degeneration. A complete knowledge of the mechanisms responsible for initiation of adventitial vessel proliferation, their extension into the intimal regions and possible de-novo synthesis of neovessels following differentiation of bone-marrow-derived stem cells is required in order to contemplate potential single or combinational anti-angiogenic therapies. In this review, we will examine the importance of angiogenesis in complicated plaque development, describe the current knowledge of molecular mechanisms of its initiation and maintenance, and discuss possible future anti-angiogenic therapies to control plaque stability. http://www.jangiogenesis.com/content/1/1/4 Mark Slevin Jerzy Krupinski Lina Badimon Vascular Cell 2009, null:4 2009-09-21T00:00:00Z doi:10.1186/2040-2384-1-4 /content/figures/2040-2384-1-4-toc.gif Vascular Cell 2045-824X ${item.volume} 4 2009-09-21T00:00:00Z XML Angiogenesis is a crucial process in tumor pathogenesis as it sustains malignant cells with nutrients and oxygen. It is well known that tumor cells secrete various growth factors, including VEGF, which triggers endothelial cells to form new capillaries. Prevention of expansion of new blood vessel networks results in reduced tumor size and metastasis. Production of VEGF is driven by hypoxia via transcriptional activation of the VEGF gene by HIF-1α.Tumours are now understood to contain different types of cells, and it is the cancer stem cells that retain the ability to drive the tumour's growth. They are called cancer stem cells because, like stem cells present in normal tissues of the body, they can self-renew and differentiate. These cancer stem cells are responsible for the relapse of cancer as they are found to be resistant to conventional modes of cancer therapy like chemotherapy and radiation.In this review, a novel mode of treatment of cancer is proposed, which utilizes the twin nanoparticle to target endothelial cells in the niche of cancer stem cell. The nanoparticle discussed in this review, is a twin nanoparticle of iron coated with gold, which targets VEGF positive cell in the vicinity of cancer stem cell. In the twin nanoparticle, one particle will recognize cancer stem cell, and another conjugated nanoparticle will recognize VEGF positive cells, thereby inhibiting endothelial cells in the proximity of cancer stem cell. This novel strategy will inhibit angiogenesis near cancer stem cell hence new tumour cannot grow and old tumour will be unable to metastasize. http://www.vascularcell.com/content/3/1/26 Rashmi Ambasta Archita Sharma Pravir Kumar Vascular Cell 2011, null:26 2011-11-14T00:00:00Z doi:10.1186/2045-824X-3-26 /content/figures/2045-824X-3-26-toc.gif Vascular Cell 2045-824X ${item.volume} 26 2011-11-14T00:00:00Z XML