Biomedical subjects

A Orpana

Publications and source records attributed to A Orpana.

35 records · Page 2Linked to original sources

PubMed1999

Vascular endothelial growth factor is bound in amniotic fluid and maternal serum.

To study vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) concentrations and their possible binders, serum from 22 non-pregnant and 55 pregnant women (15 at weeks 10-13; 40 at term), umbilical vein (n = 24) and artery (n = 13) and amniotic fluid (a pool of 50 at weeks 15-17; 11 at term) were assessed for VEGF and PlGF by an enzyme-linked immunosorbent assay. In amniotic fluid and maternal serum VEGF concentrations were <16 ng/ml and added VEGF was not recovered. VEGF was detected in serum from mothers post-partum (137 +/- 142 ng/l, mean +/- SD), umbilical artery (421 +/- 288 ng/l) and vein (502 +/- 339 ng/l) and non-pregnant controls (182 +/- 147 ng/l), and added VEGF was fully recovered. PlGF was detected in pregnancy serum (52 +/- 23 ng/l early pregnancy; 439 +/- 217 ng/l term pregnancy) and in amniotic fluid (early pregnancy 56 ng/l; term pregnancy 30 +/- 18 ng/l). PlGF was fully recovered in all samples. Gel filtration and isoelectric focusing revealed that in maternal serum and amniotic fluid [125I]VEGF was bound to a protein with an Mr of 400-700 kDa and an isoelectric point of approximately 8. This protein was not identical with alpha-2-macroglobulin (by an immunofluorometric assay), pregnancy zone protein or pregnancy associated plasma protein-A (by immunodiffusion). In conclusion, VEGF-binding activity is present in amniotic fluid and maternal blood. It disappears after delivery and is not detectable in fetal or non-pregnant serum.

Adolescent↗

PubMed1999

Human vascular endothelial cells produce tumor necrosis factor-alpha in response to proinflammatory cytokine stimulation.

OBJECTIVE: To determine whether human vascular endothelial cells produce tumor necrosis factor-alpha (TNF-alpha) after stimulation with proinflammatory cytokines and bacterial lipopolysaccharides (LPS). DESIGN: Prospective, in vitro repeated-measurements analysis of cellular responses. SETTING: Research laboratory in an academic medical center. SUBJECTS: Human umbilical vein endothelial cells (HUVECs). INTERVENTIONS: HUVECs were incubated with interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), and LPS, or their different combinations for 2 to 48 hrs. MEASUREMENTS AND MAIN RESULTS: TNF-alpha was measured by time-resolved immunofluorometric assay. Unstimulated HUVECs did not produce detectable amounts of TNF-alpha, but IFN-gamma, IL-1beta, and LPS when added together induced TNF-alpha production of HUVECs in a time-dependent manner. Immunofluorescent staining confirmed that the TNF-alpha was produced by endothelial cells. IFN-gamma, IL-1beta, or LPS alone did not induce TNF-alpha production, whereas IFN-gamma and IL-1beta in combination were able to induce TNF-alpha production to some extent, and the production could be further increased with LPS. TNF-alpha messenger RNA expression was detected with reverse transcriptase-coupled polymerase chain reaction in stimulated, but not in unstimulated, HUVECs. CONCLUSIONS: HUVECs are capable of producing TNF-alpha after proinflammatory cytokine stimulation and may therefore contribute to the increased amount of TNF-alpha found in pathologic states such as septic shock.

Cell Count↗

PubMed1999

Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen and permeability factor. Malignant human tumors have been shown to produce VEGF. Elevated levels of VEGF have been detected in sera of cancer patients, but its origin is unsettled. We analyzed VEGF concentrations in serum, plasma, whole blood, and peripheral blood mononuclear cells (PBMNCs) and platelets in 56 cancer patients and 52 healthy controls using ELISA. The VEGF concentrations in the lysed whole blood samples [blood VEGF (B-VEGF)] were higher in cancer patients than in healthy controls (median, 464 versus 298 pg/ml; P<0.0001). The highest B-VEGF values were found in disseminated cancer. In cancer patients, a high B-VEGF concentration was associated with a high peripheral blood leukocyte count (P = 0.0012) and platelet count (P = 0.019). In healthy individuals, a high B-VEGF was associated with a high leukocyte count (P = 0.0001) but not with the platelet count (P>0.1). The cancer patients regularly had higher B-VEGF concentrations than healthy individuals with comparable leukocyte or platelet counts. The VEGF content of isolated PBMNCs and platelets was severalfold higher in cancer patients than in healthy controls (median, 10.6 versus 0.9 pg per 10(6) PBMNCs, and median, 1.6 versus 0.5 pg per 10(6) platelets; P<0.0001 and P = 0.0008, respectively). Serum VEGF and B-VEGF correlated strongly (P<0.0001). Very little or no VEGF was found in the plasma. The results indicate that VEGF in the bloodstream is transported by blood cells, including leukocytes and platelets. The blood cells of cancer patients contain greatly elevated amounts of this major angiogenic growth factor, and this reservoir of VEGF may have a role in tumor angiogenesis and metastasis formation. VEGF in serum samples originates from blood cells, and the use of VEGF of whole blood or of isolated blood cells may improve the clinical value of VEGF measurements.

Adolescent↗

PubMed1999

Markers of systemic inflammation predicting organ failure in community-acquired septic shock.

To obtain predictors of organ failure (OF), we studied markers of systemic inflammation [circulating levels of interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R), soluble E-selectin and C-reactive protein, and neutrophil and monocyte CD11b expression] and routine blood cell counts in 20 patients with systemic inflammatory response syndrome and positive blood culture. Eight patients with shock due to community-acquired infection developed OF, whereas 11 normotensive patients and one patient with shock did not (NOF group). The first blood sample was collected within 48 h after taking the blood culture (T1). OF patients, as compared with NOF patients, had at T1 a lower monocyte count, a lower platelet count, higher levels of CD11b expression on both neutrophils and monocytes, and higher concentrations of IL-6, IL-8 and sIL-2R. C-reactive protein and soluble E-selectin concentrations did not differ between groups. No parameter alone identified all patients that subsequently developed OF. However, a sepsis-related inflammation severity score (SISS), developed on the basis of the presence or absence of shock and on the levels of markers at T1, identified each patient that developed OF. The maximum SISS value was 7. The range of SISS values in OF patients was 2-5, and that in NOF patients was 0-1. In conclusion, high levels of CD11b expression, depressed platelet and monocyte counts, and high concentrations of IL-6, IL-8 and sIL-2R predict OF in patients with community-acquired septic shock, and the combination of these markers may provide the means to identify sepsis patients who will develop OF.

APACHE↗

PubMed1998

Reduced viability of human vascular endothelial cells cultured on Matrigel.

Optimal vascular homeostasis requires efficient control of both proliferation and elimination of vascular endothelial cells. Programmed cell death, or apoptosis, is the main mechanism controlling cell elimination, and it is an essential component of vascular formation. Human vascular endothelial cells die in vitro, if prevented from obligatory survival factors like growth factors or attachment and cell spreading, but very little is known about the mechanisms controlling endothelial cell elimination. Signaling from the extracellular matrix affects the behavior and functions of human umbilical vein endothelial cells (HUVECs), and we have recently demonstrated the beneficial effects of plating on the reconstituted extracellular matrix Matrigel, on the inducible nitric oxide production of freshly isolated HUVECs. In this work we observed that cultured HUVECs formed typical capillary-like structures on Matrigel, but unexpectedly, after 24-48 hours their viability was gradually lost. Viability was measured with an assay based on mitochondrial reduction of reagent XTT. No decrease in viability was seen in freshly isolated HUVECs or in cultured fibroblasts during this time. It is known that cells often turn into apoptosis if they receive conflicting information from their surroundings, and apparently signaling from Matrigel to HUVECs, while at their in vitro proliferating phenotype, resulted in launching of the apoptotic machinery. Thus, proliferating and differentiated phenotypes of endothelial cells seemed to have different sensitivity to signals that induce apoptosis.

Apoptosis↗

PubMed1998

Peripheral blood platelets express VEGF-C and VEGF which are released during platelet activation.

VEGF-C is a recently characterised endothelial growth factor structurally related to vascular endothelial growth factor (VEGF). We studied the expression of VEGF-C and VEGF in the cells of peripheral blood and in the umbilical cord blood CD 34+ cells, representing haematopoietic progenitor cells. Expression of VEGF-C was detected in the CD34+ cells. In peripheral blood VEGF-C mRNA was restricted to platelets and T-cells. In contrast to the expression pattern of VEGF-C, VEGF mRNA was detected in all peripheral blood cell fractions studied, and also in CD34+ cells. VEGF-C mRNA was also detected in fresh bone marrow samples of acute leukaemia patients, but the expression did not show lineage specificity. VEGF-C and VEGF polypeptides were present in platelets and they were released from activated platelets together with the release of beta-thromboglobulin, suggesting that VEGF-C and VEGF reside in the alpha-granules of platelets. VEGF-C and VEGF, released from activated platelets, may have a role in angiogenesis during wound healing, and possibly also in other pathological conditions, such as atherosclerosis, tumour growth, and metastasis formation.

Amino Acid Sequence↗

PubMed1997

Inducible nitric oxide and prostacyclin productions are differently controlled by extracellular matrix and cell density in human vascular endothelial cells.

Both cell-matrix and cell-cell interactions are important regulators of the function of most human cells. In this study we investigated how these interactions controlled the production of vasodilators nitric oxide (NO), and prostacyclin (PGI2), in freshly isolated human umbilical vein endothelial cells (HUVECs). On the reconstituted extracellular matrix (ECM) Matrigel freshly isolated HUVECs treated with interleukin-1 beta, lipopolysaccharide, and interferon-gamma, produced more NO, but less PGI2, than on gelatin substratum. High cell density was essential for inducibility of NO production in cells plated on gelatin substratum, but not on ECM. In cells plated on gelatin substratum at low cell density, which mimicked conventional HUVEC culturing conditions, both inducible NO production and the inducible NO synthase (iNOS) mRNA levels, detected by competitive RT-PCR, were low. However, inducible PGI2 production remained high in these cells. Highest inducible NO productions were observed in HUVECs that presumably had best maintained their original differentiated phenotype. Thus our data imply that the inducible NO and PGI2 productions of freshly isolated HUVECs were differently controlled by the extracellular matrix and cell density. Our data suggest that both cell-matrix and cell-cell interactions may have a strong influence on the proinflammatory cytokine responses of human vascular endothelial cells.

Cell Communication↗

PubMed1997

Different effects of oral and transdermal hormonal replacement on prostacyclin and thromboxane A2.

OBJECTIVE: To elucidate the mechanism of cardiovascular protection of hormone replacement therapy (HRT) by comparing the effect of oral and transdermal HRTs on the production of antiaggregatory, vasodilatory prostacyclin, and its endogenous antagonist, thromboxane A2. METHODS: Oral estradiol (2.0 mg/d) plus norethisterone acetate (1.0 mg/d) (n = 13) or transdermal estradiol (50 micrograms/d) plus medroxyprogesterone acetate (10 mg/d) as 12-day courses at 4-week intervals (n = 13) were given to postmenopausal women. Urinary excretion of the metabolites of prostacyclin, ie, 6-ketoprostaglandinF1 alpha and 2,3-dinor-6-ketoprostaglandinF1 alpha, as well as those of thromboxane A2, ie, thromboxane B2 and 2,3-dinor-thromboxane B2, were measured by radioimmunoassays, after purification by extraction and high performance liquid chromatography, before and during the sixth and the 12th treatment cycles. RESULTS: Oral HRT stimulated excretion of thromboxane B2 from 3.4 +/- 0.7 ng/mmol creatinine to 4.5 +/- 1.5 (mean +/- standard deviation, P < .05) and that of 2,3-dinor-thromboxane B2 from 16.6 +/- 8.0 ng/mmol creatinine to 26.2 +/- 10.7 (P < .01), and thus led to the dominance of thromboxane A2. No changes in prostanoids occurred during transdermal HRT. CONCLUSIONS: The effects of various HRTs on prostanoids may significantly differ.

Administration, Cutaneous↗

PubMed1997

Culturing of human vascular endothelial cells strongly affects their endothelin-1 and prostacyclin production.

Cultured human umbilical vein endothelial cells (HUVECs) are a widely used model to study the regulation of endothelial production of vasoactive substances such as endothelin-1 (ET-1) and prostacyclin (PGI2) in human. As even short term culturing is known to affect the function of many cell types, we studied whether there are differences in the production of ET-1 and PGI2 between freshly isolated HUVECs and HUVECs cultured for two passages, and whether variation in cell density affects the production of ET-1 and PGI2 by these cells. At confluency, freshly isolated HUVECs produced only from one-tenth to one-fifth of ET-1, but 46-86 times more PGI2 (p < 0.001), when compared to respective productions by similar amounts of cultured HUVECs. When the cell density of freshly isolated HUVECs was lowered either by diluting the cell suspension or by plating the same amount of cells on different size wells, the production of ET-1 increased: lowering cell density to one-tenth led to 18 fold increase in ET-1 production (p < 0.001). PGI2 production was not affected by cell density. Thus our data imply that the production of both ET-1 and PGI2 are differently regulated in freshly isolated and cultured HUVECs, and that cell density is an important determinant in the regulation of ET-1 production.

Cell Culture Techniques↗

PubMed1997

High endothelin-1 in the airways of preterm infants is associated with less severe respiratory distress during the early postnatal period.

OBJECTIVE: To study the relationship between endothelin-1 (ET-1) in the airways and respiratory distress in preterm infants. METHODS: ET-1 was determined in 60 tracheal aspirates from 11 preterm intubated infants (gestational age 28.0 +/- 2.5 weeks) during the first week of life. RESULTS: The concentration of ET-1 of the aspirates was 6 to 2760 pg/mL (median 293 pg/mL). Negative correlations existed between mean log ET-1 and mean airway pressure (R2 = .812) and fraction of inspired oxygen (R2 = .591), whereas a positive correlation was found between the arteriolar/alveolar oxygenation ratio within 3 hours of birth and mean log ET-1 on the first day (R2 = .555). CONCLUSION: The association of high ET-1 in the airways with less severe respiratory distress in the early postnatal period may be attributable to effects of ET-1 on surfactant secretion or development of airway epithelium.

Endothelin-1↗

PubMed1997

Serum vascular endothelial growth factor is often elevated in disseminated cancer.

In adults, marked angiogenesis takes place only during the female reproductive cycles, during wound healing, and accompanying some disease processes, such as tumor development. Vascular endothelial growth factor (VEGF) is a secreted, endothelial cell-specific growth factor, which is induced by tissue hypoxia and is angiogenic in vivo. We measured serum VEGF (S-VEGF) concentrations by ELISA in patients with a variety of types of cancer, as well as in healthy volunteers, and in patients with diabetes or rheumatoid arthritis. Elevated S-VEGF concentrations were found in patients with locoregional (n = 39; median, 158 pg/ml; range, 8-664 pg/ml) or disseminated (n = 58; median, 214 pg/ml; range, 17-1711 pg/ml) cancer in comparison to individuals without cancer (n = 113; median, 17 pg/ml; range, 1-177 pg/ml; P < 0.0001 for both comparisons). Values higher than 200 pg/ml were observed in 74% of patients with untreated metastatic cancer, and high serum levels were measured regardless of the histological type of cancer. S-VEGF levels were found to be higher in untreated patients with disseminated cancer than in those with local cancer (P = 0.006), and patients undergoing cancer therapy had lower values than those without cancer therapy (P = 0.03). The results indicate that both patients with locoregional cancer and patients with disseminated cancer may have elevated S-VEGF levels, regardless of the histological type of cancer, and that S-VEGF is often elevated in cancer with distant metastases.

Adult↗

PubMed1996

Vascular endothelial growth factor B, a novel growth factor for endothelial cells.

We have isolated and characterized a novel growth factor for endothelial cells, vascular endothelial growth factor B (VEGF-B), with structural similarities to vascular endothelial growth factor (VEGF) and placenta growth factor. VEGF-B was particularly abundant in heart and skeletal muscle and was coexpressed with VEGF in these and other tissues. VEGF-B formed cell-surface-associated disulfide-linked homodimers and heterodimerized with VEGF when coexpressed. Conditioned medium from transfected 293EBNA cells expressing VEGF-B stimulated DNA synthesis in endothelial cells. Our results suggest that VEGF-B has a role in angiogenesis and endothelial cell growth, particularly in muscle.

Amino Acid Sequence↗

PubMed1996

Effect of physiological concentrations of estradiol on PGI2 and NO in endothelial cells.

OBJECTIVES: To elucidate the mechanisms by which estrogens protect against occlusive vascular disorders, we studied the effect of 17 beta-estradiol on the production of prostacyclin (PGI2) and nitric oxide (NO) in primary cultures of human umbilical vein endothelial cells (HUVECs). METHODS: To study the effect of 17 beta-estradiol on PGI2 production, HUVECs were incubated in the absence and presence of 17 beta-estradiol (0.01-10 nmol/l) encapsulated within beta-cyclodextrin for 12 h in serum-free medium. To study the effect of 17 beta-estradiol (100 nmol/l) on maximal calcium-dependent NO production, we used different approaches. First, HUVECs were incubated with 2 mumol/l calcium ionophore A23187 with or without 17 beta-estradiol (100 nmol/l) for 24 h in serum-free medium. Second, HUVECs were preincubated with or without 17 beta-estradiol (100 nmol/l) for 12 h in medium supplemented with 2% fetal calf serum, and thereafter incubated in serum-free medium with 2 mumol/l of A23187 and with 100 nmol/l of 17 beta-estradiol (cells which contained 17 beta-estradiol during the preincubation period as well as cells which did not) or without it (only cells which did not contain 17 beta-estradiol during the preincubation period) for 6 h or 24 h. RESULTS: 17 beta-Estradiol (0.1 nmol/l) increased the concentration of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2 in the incubation medium, by 16%, and no further increase occurred with higher 17 beta-estradiol concentrations. The stimulation was prevented by tamoxifen. 17 beta-Estradiol did not affect NO production in any of our experiments measured as accumulation of nitrate and nitrite in the experimental medium. CONCLUSIONS: The stimulatory effect on PGI2 production of physiological concentrations of 17 beta-estradiol, shown now for the first time, may provide one explanation for the ability of 17 beta-estradiol to protect against occlusive vascular disorders.

Culture Techniques↗

PubMed1996

Hormone replacement therapy modifies the capacity of plasma and serum to regulate prostacyclin and endothelin-1 production in human vascular endothelial cells.

OBJECTIVE: To determine if hormone replacement therapy (HRT) modifies the ability of plasma or serum to regulate the synthesis of vasodilatory prostacyclin and that of vasoconstrictive endothelin-1 by cultured human umbilical vein endothelial cells. DESIGN: Plasma and serum collected before and during the sixth treatment cycle of HRT from 13 healthy postmenopausal women were added to cultured endothelial cells. SETTING: Helsinki University Central Hospital, Department of Obstetrics and Gynecology, Helsinki, Finland. PATIENTS: Thirteen postmenopausal women (> or = 1 year since their last menstruation, FSH level > 40 mIU/mL [conversion factor to SI unit, 1.00], clear vasomotor symptoms) that suffered from incapacitating menopausal symptoms necessitating the initiation of HRT were studied. INTERVENTIONS: A combined regimen consisting of 2 mg oral E2 for 12 days followed by 2.0 mg oral E2 + 1.0 mg norethisterone acetate for 10 days and 1.0 mg E2 for 6 days. MAIN OUTCOME MEASURES: The releases of prostacyclin, as assessed by its metabolite 6-keto-prostaglandin F1 alpha, and that of endothelin-1 by cultured human umbilical vein endothelial cells in the presence of 10% plasma or 10% serum collected from the study subjects. RESULTS: Hormone replacement therapy enhanced the ability of plasma to stimulate prostacyclin production by 21% +/- 6% (mean +/- SEM) during the E2 + norethisterone acetate phase and tended to do so also during the E2-only phase (11% +/- 10%) but caused no change in endothelin-1 release. In contrast, HRT decreased the ability of serum to stimulate prostacyclin production by 12% +/- 5% during the E2-only phase and increased that of endothelin-1 by 8% +/- 4% during the E2 + norethisterone acetate phase. CONCLUSION: Because plasma flushes endothelial cells in vivo, our data on the HRT-induced stimulation of the capacity of plasma to enhance the production of vasoprotective prostacyclin without a concomitant change in endothelin-1 release in cultured human umbilical vein endothelial cells may provide one new explanation for the cardiovascular protection of HRT.

Blood Physiological Phenomena↗

PubMed1995

Postmenopausal hormonal replacement decreases plasma levels of endothelin-1.

Hormone replacement therapy (HRT) protects against cardiovascular disorders, but the mechanisms of this action are poorly understood. We assessed the plasma levels of vasoconstrictive endothelin-1 (ET-1) in 26 healthy postmenopausal women before and during HRT. The women were randomized to receive either continuous transdermal (estradiol 50 ug/24 hrs) complemented with periodic 12 days' courses with medroxyprogesterone (10.0 mg/day)(n = 13) or continuous oral estradiol (2.0 mg/day) and continuous norethisterone acetate (1.0 mg/day)(n = 13). ET-1 was measured with specific radioimmunoassay after concentrating the sample with solid phase extraction. Pretreatment plasma ET-1 (1.28 +/- 0.36 pmol/ml, mean +/- SD) in the whole study group decreased (p < 0.01) to 1.05 +/- 0.26 pmol/ml at 6 months and to 1.10 +/- 0.32 pmol/ml at 12 months of treatment. A subgroup analysis between the two HRT regimens revealed no significant differences in the response of plasma ET-1 to HRT. These first data on HRT-induced reduction in plasma ET-1 may provide a new explanation for the cardiovascular protection by HRT.

Administration, Cutaneous↗

PubMed1995

17 beta-estradiol stimulates prostacyclin, but not endothelin-1, production in human vascular endothelial cells.

The exact mechanisms by which estrogens protect against occlusive vascular disorders are not known. One possibility could be an effect on vascular endothelial vasoactive compounds, such as vasodilatory prostacyclin (PGI2) and vasoconstrictory endothelin (ET-1). Here we report on the effect of 17 beta-estradiol on the synthesis of PGI2 and ET-1 in cultured human umbilical vein endothelial cells. These cells were incubated in the absence (control) and presence of 17 beta-estradiol (0.001-1 mumol/L) for 3-24 h with serum (10%) or without serum. The release of PGI2, as assessed by its metabolite 6-keto-prostaglandin F1 alpha, and that of ET-1, were assessed by RIA. 17 beta-Estradiol (0.01-0.1 mumol/L) predissolved in ethanol (final concentration, 0.01%) increased PGI2 production by 26-30% in endothelial cells incubated without serum. This increase in PGI2 production was enhanced up to 66% when 17 beta-estradiol (1 mumol/L) was encapsulated within beta-cyclodextrin. The stimulation of PGI2 production was detectable after 12 h of incubation. The 17 beta-estradiol-induced stimulation of PGI2 production was blocked in dose-dependent manner by antiestrogenic tamoxifen. 17 beta-Estradiol failed to affect the production of PGI2 if the endothelial cells were incubated with serum and had no effect on ET-1 production under any conditions. 17 beta-Estradiol-induced stimulation of vasodilatory and antiaggregatory PGI2 production without a concomitant change in vasoconstrictory ET-1 production may provide one explanation for the ability of estradiol to maintain vascular health and protect against vascular disorders.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells.

Transforming growth factor beta (TGF-beta) is a multifunctional polypeptide that regulates the proliferation and differentiation of various cells and has an angiogenic effect in vivo, although it inhibits the growth of cultured endothelial cells. We report here that TGF-beta treatment of quiescent cultures of mouse embryo-derived AKR-2B cells, which are growth-stimulated by TGF-beta, and human lung adenocarcinoma A549 cells, which are growth-inhibited by TGF-beta, results in the induction of vascular endothelial growth factor (VEGF) mRNA and protein. Maximal VEGF mRNA levels occurred 4-8 h after stimulation with a decline to background levels in 24 h. In contrast, the related placenta growth factor mRNA was not induced by TGF-beta in these cells. No VEGF receptor mRNA was seen in AKR-2B cells. Also, TGF-beta treatment of endothelial cells, which express the FLT1 and KDR/FLK-1 receptors for VEGF, did not cause VEGF induction. Because VEGF is known to be a strong angiogenic factor for endothelial cells, the results suggest that the angiogenic effect of TGF-beta on endothelial cells in blood vessels may be mediated at least partly by a paracrine induction of VEGF in other surrounding cell types.

Animals↗