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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review focuses on a spectrum of inherited disorders in which recent genetic advances have made a significant contribution to our understanding of vascular pathology and homeostasis. They are discussed according to the type of blood vessel affected and the compounded physiological processes that include angiogenesis, vascular development, and defects in the structure and regulation of the mature vessel. Vascular malformations, arterial aneurysms and dissection, telangiectasia, infiltrative vascular disease, and inherited tumors and disorders of neovascularization are discussed in a variety of settings. Disease roles for endoglin, tissue inhibitor of metalloproteinases 3 (TIMP3), and vascular endothelial growth factor (VEGF) dysregulation are highlighted (175 references).
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PMID:Inherited diseases of the vasculature. 881 4

Glucocorticoid (GC) use is known to induce or enhance the growth of Kaposi's sarcoma (KS) in many clinical settings including human immunodeficiency virus infection, collagen vascular disease, lymphoproliferative disorders, and renal transplantation. Because GCs may induce immune suppression and thus tumor growth, we determined whether GCs had a direct effect on KS growth. We found that GCs directly induce the growth of KS cell lines. In examining the mechanism of action of GCs, we did not observe induction of known autocrine growth factors for KS including interleukin-1 (IL-1), IL-6, oncostatin-M, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF). We thus examined factor(s) that inhibit KS growth. Transforming growth factor-beta (TGF-beta) is produced by KS cells and has pleiotropic effects, including inhibiting the growth of hematopoietic and endothelial cells. We show that TGF-beta is produced by KS cells in both the latent and active forms, and that TGF-beta is an autocrine growth inhibitory factor. We then studied the effects of GCs on the regulation of TGF-beta and found that GCs do not inhibit TGF-beta transcription, but significantly inhibit TGF-beta activation. This effect is mediated through regulation of the TGF-beta activation pathway. TGF-beta is activated by plasmin which is positively regulated by plasminogen activator (PA) and PA receptor (PAR), and negatively regulated by plasminogen activator inhibitor (PAI). GCs downregulated PAR and upregulated PAI. Thus, glucocorticoids enhance KS cell growth through the regulation of TGF-beta activation.
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PMID:Glucocorticoids induce Kaposi's sarcoma cell proliferation through the regulation of transforming growth factor-beta. 905 28

Cardiovascular disease and cancer account for the majority of adult disease in the developed world. This review focuses on current concepts in the study of angiogenesis (new vessel formation) as related to these conditions and highlights the role of vascular endothelial growth factor. Developments in therapeutic angiogenesis have raised the possibility that pharmacologic or gene-directed interventions, based on the ability of vascular endothelial growth factor to promote new vessel formation, may soon gain clinical application for the treatment of occlusive vascular disease. Similarly, the future treatment of malignant disease is likely to involve antiangiogenic agents that, in preliminary animal work, have demonstrated an efficacy that is not limited by adverse affects. Aside from these potential applications, current investigations have enhanced our understanding of mechanisms involved in the development of atherosclerotic and malignant disease.
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PMID:Angiogenesis in the pathobiology and treatment of vascular and malignant diseases. 935 65

Growth factors such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) exert important effects on endothelial cells in vitro and in vivo. This article reviews the effect of these two growth factors on endothelial dysfunction in various animal models of vascular disease: (1) collateral circulation supplying an ischemic territory, (2) balloon injury, and (3) diet-induced experimental atherosclerosis. Endothelial dysfunction may limit the beneficial effects of collateral vessels on tissue perfusion. Administration of VEGF or basic FGF (bFGF) augments collateral development in different models of hindlimb ischemia by enhancing neovascularity and by facilitating the recovery of endothelial function in the collateral circulation. Similarly, studies performed after balloon angioplasty have demonstrated abnormal responses of previously dilated sites to endothelium-dependent agonists. Administration of VEGF or bFGF increases endothelial regrowth and normalizes endothelium-dependent responses after experimental angioplasty. Finally, endothelium-dependent relaxation is impaired in diet-induced experimental atherosclerosis. It was recently demonstrated that hypercholesterolemic rabbits treated with bFGF had significantly better endothelium-dependent responses than those not treated with bFGF. These results show that in vivo administration of the endothelial cell growth factors VEGF and bFGF leads to significant improvement in endothelium-dependent responses and supports the concept of using these growth factors as a new therapeutic strategy for patients with vascular diseases.
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PMID:Growth factors as a potential new treatment for ischemic heart disease. 942 53

The role of nutrient supply in the replicative capacity and secretory phenotype of cultured human diploid cells is unclear. We examined the relationship between amino acid privation, the secretion of vascular endothelial growth factor (VEGF) and growth phenotype of vascular smooth muscle cells (VSMC), and endothelial cells. Cultures of VSMCs, but not endothelial cells, were growth inhibited by exposure to medium that was 75% deficient in leucine, methionine, arginine, and cysteine over two passages. Exposed VSMC cultures exhibited an increased vulnerability to apoptosis. The maximal cumulative population doubling of the exposed cells was reduced significantly compared with the control cells (25.7 +/- 2.0 doublings vs. 27.9 +/- 2.1 doublings; P < 0.03). Constitutive VEGF production first became evident in the later passages of the exposed and nonexposed cell cultures. However, production of VEGF was 17-fold greater in the exposed cultures at the tenth passage (P < 0.001). The replicative capacity and constitutive production of VEGF in VSMCs in culture may be programmed by transient privation of amino acids. These observations are relevant to new concepts concerning the pathogenesis of vascular disease.
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PMID:Amino acid depletion modulates vascular endothelial growth factor production during the life span of human vascular smooth muscle cells. 964 23

Platelet aggregation is a cardinal feature of both vascular repair and vascular disease. During aggregation platelets release a variety of vasoactive substances; some of these promote angiogenesis, endothelial permeability, and endothelial growth, actions shared by vascular endothelial growth factor (VEGF). This study was undertaken to investigate the hypothesis that VEGF is released by aggregating platelets. We found that VEGF was secreted during the in vitro aggregation of platelet-rich plasma induced by thrombin, collagen, epinephrine, and ADP (range 23-518 pg VEGF/ml). Furthermore, serum VEGF levels were elevated compared with plasma (230 +/- 63 vs. 38 +/- 8 pg VEGF/ml), indicative of VEGF release during whole blood coagulation. Lysates of apheresed, leukocyte-poor platelet units contained significant amounts of VEGF (2.4 +/- 0.8 pg VEGF/mg protein). VEGF message and protein were also present in a megakaryocytic cell line (Dami cell). These results suggest constitutive roles for platelet VEGF in the repair of intimal vessel injury and in the altered permeability and intimal proliferation seen at sites of platelet aggregation and thrombosis.
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PMID:In vitro release of vascular endothelial growth factor during platelet aggregation. 972 13

Angiogenic growth factors constitutes a potentially novel form of therapy for patients with ischemic vascular disease. The feasibility of using recombinant formulations of angiogenic growth factors to augment collateral artery development by stimulation of capillary growth in animal models of myocardial and hindlimb ischemia has now been well established. In the case of vascular endothelial growth factor (VEGF) similar results may be achieved by gene transfer. Further laboratory and clinical studies may yield promising insights into the fundamental basis for native as well as therapeutic angiogenesis, and at the same time more explicitly define the manner in which therapeutic angiogenesis may be successfully incorporated into clinical practice.
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PMID:Stimulation of peripheral angiogenesis by vascular endothelial growth factor (VEGF). 985 38

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have shown strong angiogenetic effects in ischemic animals; however, whether such a beneficial effect could be achieved using low doses remains to be determined. The effects of identical low-level doses of these substances on the creation of collateral circulation in canine acute hind limb insufficiency were evaluated. Anesthetized dogs that had undergone left femoral artery occlusion received 20 microg (2 microg/kg) intravenous boluses of either bFGF or VEGF 3 times at 2-day intervals for the first week only, animals on vehicle saline injection served as controls. All groups, control (n=8), bFGF-treated (n=8), and VEGF-treated (n=6) underwent angiography, blood flow measurement (in ml/min) on the day of ligation (day 0), and at 7, 14 and 28 days, then underwent ischemic limb muscle biopsy at 28 days. Angiogenic-treated groups showed remarkable enhanced collateral circulation at 7 days, which was maintained up to 28 days, and the main collateral source artery of the angiogenic-treated groups dilated by 14 days. Many neovascularized arterioles in specimens of the angiogenic groups were recognized without any tissue edema or necrosis. Even low doses of bFGF or VEGF were enough to augment collateral circulation with no side-effects, and short treatment after acute ischemia was effective. Low-dose bFGF or VEGF may be therapeutical effective options in patients with acute lower limb vascular disease.
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PMID:Low-dose basic fibroblast growth factor and vascular endothelial growth factor for angiogenesis in canine acute hindlimb insufficiency. 989 Feb 8

Neovascularization of the atherosclerotic plaque is responsible for its weakening and consequently for the complications of vascular disease. Macrophages are a source of growth factors that can modulate angiogenesis. In this study, we analyzed the effect of oncostatin M (OSM) on angiogenesis, as it could be involved in the development of atherosclerosis. The effect of OSM was compared with those of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). On human dermal microvasculature endothelial cells (HMEC-1s), OSM (22.5 to 112.5 pmol/L) induced a dose-dependent increase in cell proliferation greater than that induced by the classic angiogenic factors vascular endothelial growth factor (VEGF; 543 pmol/L) and basic fibroblast growth factor (bFGF; 1.1 nmol/L). LIF (19 to 475 pmol/L) induced only a 30% increase in cell proliferation, and IL-6 had no effect. Furthermore, in a modified Boyden-chamber model, OSM, LIF, and IL-6 were chemoattractant for HMEC-1s. In a tridimensional gel of fibrin, OSM increased tube formation and tube length, which were already noticeable by day 3. LIF and IL-6 induced a weaker effect that was only obvious by day 10. The angiogenic effect of OSM was also demonstrated in vivo in a rabbit corneal model: OSM was more potent than LIF, the length of the neovessels being longer with OSM than with LIF, whereas IL-6 was without effect. We tested factors that could be involved in the proliferative effect of OSM on HMEC-1s. OSM induced only a slight increase in the urokinase receptor and a 60% increase in VEGF secretion, whereas it does not modify IL-8 secretion or bFGF levels. The effect of OSM seems to depend on endothelial cell origin and cell species: OSM (up to 112.5 pmol/L) did not induce human umbilical vein endothelial cell proliferation and even had a small inhibitory effect (17%) on calf pulmonary artery endothelial cells. In conclusion, OSM induces an angiogenic effect on capillary endothelial cells, which could be, at least in part, implicated in pathological processes such as atherosclerosis or tumor growth.
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PMID:Oncostatin M induces angiogenesis in vitro and in vivo. 1044 61

Critical ischemia of the limbs or myocardium is frequently accompanied by diffuse distal vascular disease making it unapproachable by conventional revascularization techniques. Pharmacological treatment is available for coronary artery disease but there has been no effective medical therapy for advanced ischemia of the limbs. In the search for alternative treatments for patients with diffuse distal disease, recent developments in vascular biology have directed attention towards use of vascular growth factors. Therapeutic angiogenesis has shown promising results in early clinical studies as shown by improved clinical status and in some cases angiographic studies. We employed an angiogenic strategy that utilizes enhanced vascular endothelial growth factor (VEGF) in a fibrin network, in two patients with critical limb ischemia. Objectively, we were able to demonstrate angiographically the growth of new blood vessels after administration of VEGF and fibrin composite. Fibrin glue provides for the slow release of and prolongs the availability of VEGF, thereby sustaining angiogenesis resulting in improved oxygenation of ischemic tissue. Further investigations are warranted to validate if angiogenesis may increase blood flow in patients with advanced vascular disease.
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PMID:Angiogenesis for the treatment of vascular diseases. 1068 16


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