Expression Of Vascular Permeability Factor Research Articles

Tissue expression of 165-aa vascular permeability factor after spinal cord injury is not influenced by dexamethasone administration in rats

Using immunohistochemistry, RT–PCR, and Western Blot techniques, we studied the tissue expression of the 165-aa Vascular permeability factor (VPF) after spinal cord injury (SCI) in adult Wistar rats. The results were compared according to that the animals received or non-dexamethasone, at the dose of 1 mg/kg and day after trauma. Furthermore, the different functional recovery between treated and non-treated animals was recorded. Although the administration of dexamethasone showed a beneficial effect on the functional recovery of the animals, the tissue expression of VPF after SCI is not influenced by dexamethasone administration. Therefore, the neuroprotective effect of the dexamethasone after experimental SCI is not mediated through an interference on the biological effects of the 165-aa vascular permeability factor.

Expression and Significance of Vascular Permeability Factor in Tumour Infiltrating Lymphocytes of Brain Metastases

Recently, vasogenic edema has been related to the expression of vascular permeability factor (VPF) by tumour cells in brain metastases. On the other hand, expression of VPF has been reported in inflammatory cells. Keeping in mind the current presence of tumour-infiltrating lymphocytes (TIL) in brain metastases, our objective is to study the expression and significance of VPF in TIL-cells from specimens of brain metastases. Tumour samples from 16 brain metastases associated with peritumoural edema were immunohistochemically studied for demonstration of VPF. The degree of VPF-expression by tumour cells and TIL was determined, and correlated with the degree of peritumoural edema. Our present results show that, independently of the VPF-positivity expressed by the tumour cells, VPF-expression is a constant finding in TIL-cells of brain metastases, and correlated with the amount of peritumoural edema. Our present findings suggest a role for TIL-cells in the development of vasogenic edema associated with brain metastases.

Expression of vascular permeability factor in glioblastoma specimens: correlation with tumor vascular endothelial surface and peritumoral edema.

Keeping in mind that the expression of vascular permeability factor (VPF) in astrocytic tumors has been related to tumor angiogenesis and peritumoral edema (PE), the aim of this study is to investigate the correlation between degree of VPF expression by tumor cells, and degree of PE and vascular endothelial surface (VES) in glioblastoma. Tumor tissue and neuroimaging data were studied in a series of 38 patients with glioblastoma. For each tumor, immunohistochemical and morphometric studies were performed in order to obtain a score of VPF expression, and a VES score, expressed as the CD-34 immunostained endothelial surface per each 1000 tumor cells. These parameters were related to the degree of PE. The results show that in glioblastomas there exist a clear correlation between the tumor-cell expression of VPF and VES, but we failed to obtain a significant correlation between degree of PE and degree of VES, or between degree of VPF expression and degree of PE. Our present results suggest that in glioblastomas, tumor angiogenesis is clearly related to the expression of VPF by tumor cells, but factors other than intratumoralpresence of VPF may contribute to the development of PE.

Vascular permeability factor expression in cerebellar hemangioblastomas: correlation with tumor-associated cysts.

The presence of vascular endothelial growth/permeability factor (VEG/PF) has been studied in histological specimens from a series of 16 cerebellar hemangioblastomas. In this series, the tumors were classified as presenting a macroscopic solid pattern (4 cases), a mainly solid pattern with macroscopic cysts (4 cases) or a mainly cystic pattern (8 cases). Solid tumors showed a low degree (75% of cases) or moderate degree (25% of cases) of VEG/PF positivity. The mainly solid tumors containing macroscopic cysts showed a moderate degree (50% of cases) or high degree (50% of cases) of VEG/PF positivity. Nevertheless, mainly cystic hemangioblastomas showed a high degree (87.5% of cases) or moderate degree (12.5% of cases) of VEG/PF positivity. These findings suggest that the predominance of a cystic or solid macroscopic appearance of cerebellar hemangioblastomas may be influenced by the degree of VEG/PF expression within the tumor tissue.

Relationship between telomerase activity, proliferative activity and apoptosis in placenta of normal and abnormal prengancy

Tissue hypoxia is a characteristic feature of malignant tumors and healing wounds, conditions that are associated with angiogenesis and with increased expression of vascular permeability factor (VPF; also called vascular endothelial growth factor, VEGF), a selective endothelial cell mitogen inducing microvascular hyperpermeability in vivo. We investigated the regulation of VPF/VEGF and its receptors by tissue hypoxia in normal human skin explants and in cultured skin cells in vitro. VPF/VEGF mRNA expression was dramatically upregulated in epidermal keratinocytes, dermal fihroblasts, and dermal microvessels after 24 h of skin organ culture. Hypoxia also enhanced the expression of VPF/VEGF in cultured epidermal keratinocytes and dermal microvascular endothelial cells (predominantly VPF/VEGF121 and V-PF/VEGF165) and in dermal fibroblasts (additional upregulation of VPF/VEGF189). The expression of the VPF/VEGF receptor Fit-1 was selectively induced on dermal microvessels in skin explant cultures and in dermal endothelial cell monolayer cultures under hypoxic conditions. In contrast, the KDR receptor was downregulated by hypoxia. These results suggest that hypoxia likely regulates cutaneous angiogenesis and mierovascular permeability by two distinct mechanisms: (i) Induction of VPF/VEGF in epithelial and mesenchymal cells, including endothelial cells. (ii) Differential modulation of VPF/VEGF receptor expression by microvascular endothelial cells. These mechanisms may be of importance in the pathogenesis of healing wounds and some malignant tumors that are commonly characterized by hypoxia and overexpression of VPF/VEGF.

Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential.

We studied the relation between tumour vascular density and tumour growth rate, metastatic incidence and vascular permeability factor (VPF) mRNA levels in a human xenograft model described previously. Vascular density was determined by automated image analysis. Xenografts derived from cell lines BLM and MV3 showed the highest mean vascular density (MVD), the highest in vivo growth rate, high VPF mRNA levels and rapid development of lung metastases. Xenografts of cell lines M14, Mel57 and MV1 showed a significantly lower degree of vascularization, lower in vivo growth rates and lower levels of VPF mRNA, but formed lung metastases with a similar incidence as those of BLM and MV3. Xenografts from cell line 1F6 did not form lung metastases, whereas tumours derived from a spontaneous mutant of 1F6, designated 1F6m, gave rise to lung metastases to the same extent as Mel57, M14 and MV1 tumours. MVD values in 1F6 and 1F6m xenografts, VPF mRNA levels and in vivo growth rates of 1F6 and 1 F6m xenografts, however, were similar. In conclusion, in the melanoma xenograft model vascular density is correlated with in vivo growth rate and with in vitro VPF mRNA levels, but not with the ability to metastasize.

Vascular Endothelial Growth Factor Expression is Increased in Renal Cell Carcinoma

To compare the expression of VEGF in renal cell carcinoma (RCC) and normal kidney. RT-PCR and Western blot analysis were performed on tumour and normal adjacent kidney collected from 31 patients (29 RCC and 2 oncocytomas) as well as proliferating vascular endothelial cells (VEC) in culture. Expression of 3 VEGF isoforms was detected in normal renal parenchyma and all ROC by RT-PCR, but was not apparent in proliferating VEC. In 27 RCC, Western blot analysis demonstrated 3-37 fold increases in VEGF expression when compared to normal parenchyma. Immunohistochemistry demonstrated VEGF staining of both tumour cells and adjacent vascular endothelium. Normal kidney showed no staining for VEGF. In the 2 remaining RCC and both oncocytomas VEGF was not increased. VEGF expression is increased in RCC and may have a paracrine effect in these tumours in stimulating angiogenesis.

Hypoxia Regulates the Expression of Vascular Permeability Factor/Vascular Endothelial Growth Factor (VPF/VEGF) and its Receptors in Human Skin

Tissue hypoxia is a characteristic feature of malignant tumors and healing wounds, conditions that are associated with angiogenesis and with increased expression of vascular permeability factor (VPF; also called vascular endothelial growth factor, VEGF), a selective endothelial cell mitogen inducing microvascular hyperpermeability in vivo. We investigated the regulation of VPF/VEGF and its receptors by tissue hypoxia in normal human skin explants and in cultured skin cells in vitro. VPF/VEGF mRNA expression was dramatically upregulated in epidermal keratinocytes, dermal fibroblasts, and dermal microvessels after 24 h of skin organ culture. Hypoxia also enhanced the expression of VPF/VEGF in cultured epidermal keratinocytes and dermal microvascular endothelial cells (predominantly VPF/VEGF121 and VPF/VEGF165) and in dermal fibroblasts (additional upregulation of VPF/VEGF189). The expression of the VPF/VEGF receptor Flt-1 was selectively induced on dermal microvessels in skin explant cultures and in dermal endothelial cell monolayer cultures under hypoxic conditions. In contrast, the KDR receptor was downregulated by hypoxia. These results suggest that hypoxia likely regulates cutaneous angiogenesis and microvascular permeability by two distinct mechanisms: (i) Induction of VPF/VEGF in epithelial and mesenchymal cells, including endothelial cells. (ii) Differential modulation of VPF/VEGF receptor expression by microvascular endothelial cells. These mechanisms may be of importance in the pathogenesis of healing wounds and some malignant tumors that are commonly characterized by hypoxia and overexpression of VPF/VEGF.

Activation-induced expression of vascular permeability factor by human peripheral T cells: a non-radioisotopic semiquantitative reverse transcription-polymerase chain reaction assay

Vascular permeability factor, also known as vascular endothelial growth factor (VPF/VEGF), is a disulfide-linked dimeric glycoprotein of about 40 kDa that enhances vascular permeability, induces chemotaxis and activation of monocytes/macrophages, and promotes growth of vascular endothelial cells. It has been reported that several tumor cell lines and normal cells produce VPF/VEGF. To examine the possibility of VPF/VEGF mRNA expression in human peripheral T cells and its mechanism(s) of regulation, we developed a non-radioisotopic semiquantitative reverse transcription-polymerase chain reaction (RT-PCR; VPF/VEGF, GAPDH co-amplification) assay which detects all species of VPF/VEGF mRNA alternative splicing products. T cells expressed negligible VPF/VEGF mRNA in the resting state. However, TPA markedly enhanced the expression of 121-, 165- and 189-amino-acid-containing isoforms of VPF/VEGF mRNA in T cells. Both CD4 + and CD8 + T cells expressed VPF/VEGF mRNA in response to TPA treatment. Moreover, T cell receptor stimulation with monoclonal anti-CD3 antibody with or without IL-1β enhanced VPF/VEGF mRNA expression in T cells. These findings suggest that T cell activation induces VPF/VEGF expression in the cells, resulting in induction of its biological activities.

Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma.

Solid tumors, including endometrial carcinomas, must induce a vascular stroma to grow beyond a minimal size. The mechanisms responsible for angiogenesis in endometrial carcinoma, however, are not well defined. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine that is an important regulator of tumor angiogenesis. We evaluated VPF/VEGF mRNA and protein expression, as well as VPF/VEGF receptor mRNA expression, in endometrial carcinoma. Fourteen examples of endometrial carcinoma were evaluated by in situ hybridization; in 7 cases, benign atrophic endometrium from the same patient was also examined. Histologic sections were subjected to in situ hybridization using 35S-labeled riboprobes specific for VPF/VEGF and, in a subset of cases, riboprobes specific for the VPF/VEGF receptors flt-1 and KDR. In addition, ten examples of endometrial carcinoma were evaluated for VPE/VEGF protein expression by immunohistochemistry. All 14 examples of endometrial carcinoma studied by in situ hybridization exhibited focal strong VPF/VEGF mRNA expression by tumor cells. In addition, the endothelial cells of surrounding microvessels strongly expressed flt-1 and KDR mRNAs in all ten cases examined. In contrast, no strong expression of VPF/VEGF, flt-1, or KDR mRNA was observed in the seven examples of benign atrophic endometrium studied. All ten cases of endometrial carcinoma studied by immunohistochemistry exhibited strong VPF/VEGF protein expression by tumor cells. These observations suggest that VPF/VEGF is an important angiogenic factor in endometrial carcinoma.

Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma

Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma

Translational regulation of vascular permeability factor by eukaryotic initiation factor 4E: implications for tumor angiogenesis.

Studies aimed at elucidating the function of the protein synthesis factor eukaryotic initiation factor 4E (elF-4E) have demonstrated that overexpression of this protein results in marked cell phenotypic and proliferative changes, including neoplastic transformation of cells. These data suggest that elF-4E may somehow participate in the development and progression of tumors in vivo. In order to determine how elF-4E exerts its transforming effects, we examined vascular permeability factor (VPF) levels in cells transfected with an elF-4E vector. Cells overexpressing elF-4E showed an increase in intracellular, and an average 130-fold increase in secreted VPF protein levels (CHO 0.13+/-0.12 ng/ml; CHO-4E 20.5+/-12.5 ng/ml) over control cells. HUVEC growth induction revealed these VPF levels to be biologically active. Northern analysis revealed no difference in VPF transcript between the 2 cell lines. Polysome analysis showed that the VPF message in elF-4E-transfected cells was associated with the heavy polysomal regions, whereas the VPF message was associated with light polysomes in control cells. These data strongly suggest that enhanced VPF expression is achieved through translational regulation rather than transcriptional regulation in cells overexpressing elF-4E. This indicates that elF-4E-induced VPF expression may be an important factor in some forms of tumor angiogenesis and development.

Expression of vascular permeability factor (VPFNEGF) messenger RNA by plasma cells: Possible involvement in the development of edema in chronic inflammation

Edema occurs in some types of chronic inflammation such as nasal polyps, uterine cervical polyps and gastric hyperplastic polyps. However, the factors or cellular components involved in the development of edema in chronic inflammation remain to be clarified. Recently, the gene encoding vascular permeability factor (VPF) or vascular endothelial growth factor (VEGF) and the genes encoding its receptors (kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1 [fit-1]) have been cloned. VPF/VEGF induces vascular hyperpermeability and vascular endothelial proliferation through KDR or fit-1 receptors. As there is a possibility that VPF/VEGF may play a role in the development of edema in chronic inflammation, we examined the messenger (m) RNA expression of VPF/VEGF and its receptors in nasal polyp tissues, which is an example of chronic inflammation with remarkable edema. Using northern blotting, all nasal polyp tissues examined expressed mRNA of VPF/VEGF and KDR. In situ hybridization revealed that VPF/VEGF mRNA-expressing cells were scattered in the edematous stroma of nasal polyps. In the adjacent sections, these cells showed the morphological features of plasma cells and expressed mRNA of immunoglobulin light chains. Human B cell leukemia and plasmacytoma cell lines expressed VPF/VEGF mRNA but human mast-cell leukemia and T cell leukemia cell lines did not. The alternatively spliced pattern of VPF/VEGF transcripts observed in nasal polyp tissues was consistent with that in plasmacytoma cell lines. Taken together, the VPF/VEGF mRNA-expressing cells in nasal polyps appeared to be plasma cells, suggesting that plasma cells may play an important role in the development of edema in chronic inflammation through the production of VPF/VEGF.

Expression of vascular permeability factor (vascular endothelial growth factor) by human endometrial stromal and decidual cells

Expression of vascular permeability factor (vascular endothelial growth factor) by human endometrial stromal and decidual cells

Vascular Permeability Factor (Vascular Endothelial Growth Factor) is Strongly Expressed in the Normal Male Genital Tract and is Present in Substantial Quantities in Semen

Purpose Vascular permeability factor (VPF) is a potent inducer of microvascular hyperpermeability and stimulates endothelial cell growth and angiogenesis. This study examines expression of VPF in the male genital tract. Materials and Methods Vascular permeability factor in seminal plasma was quantified by immunoassay. Vascular permeability factor mRNA and protein expression in tissue were studied by situ hybridization and immunohistochemistry. Results All seminal plasmas studied contained high levels of VPF. Prostatic and seminal vesicle epithelium labeled strongly for VPF mRNA and protein. Conclusions The strong expression of VPF in prostate and seminal vesicle and the high concentration of VPF in semen suggest an important role for this cytokine in male fertility.

Vascular permeability factor (vascular endothelial growth factor) is strongly expressed in the normal male genital tract and is present in substantial quantities in semen.

Vascular permeability factor (VPF) is a potent inducer of microvascular hyperpermeability and stimulates endothelial cell growth and angiogenesis. This study examines expression of VPF in the male genital tract. Vascular permeability factor in seminal plasma was quantified by immunoassay. Vascular permeability factor mRNA and protein expression in tissue were studied by situ hybridization and immunohistochemistry. All seminal plasmas studied contained high levels of VPF. Prostatic and seminal vesicle epithelium labeled strongly for VPF mRNA and protein. The strong expression of VPF in prostate and seminal vesicle and the high concentration of VPF in semen suggest an important role for this cytokine in male fertility.

Serum and platelet-derived growth factor-induced expression of vascular permeability factor mRNA by human vascular smooth muscle cells in vitro.

1. Endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation are key events in the pathogenesis of atherosclerosis. Vascular permeability factor (VPF), an endothelial-cell-specific multifunctional cytokine, was recently described, and has the potential to contribute to the development of endothelial dysfunction. The present study determines whether cultured human VSMCs express mRNA for VPF and whether VPF mRNA expression is influenced by human VSMC proliferation. 2. A 204 bp cDNA fragment, specific for all known variants of VPF mRNA, was cloned and used to demonstrate that human VSMCs express abundant quantities of VPF mRNA, whereas human endothelial cells do not. VPF mRNA levels were markedly diminished in non-proliferating human VSMCs. In contrast, when human VSMCs were stimulated to proliferate by exposure to serum, there was a rapid 6.6-fold increase (P < 0.01 versus time 0 h) in VPF mRNA expression, which was maximal at 3 h and persisted beyond 24 h. The magnitude of the VPF mRNA response in human VSMCs was dependent on the serum concentration. 3. Platelet-derived growth factor also increased VPF mRNA expression by human VSMCs, thus confirming that recognized growth factors for VSMCs also potently influence the VPF gene. 4. In conclusion, VPF mRNA is expressed by human VSMCs, the magnitude of VPF expression being temporally related to the proliferation of human VSMCs and the potency of the growth-promoting stimulus. We propose that VPF produced by proliferating human VSMCs could act as a paracrine hormone to powerfully influence the permeability and growth of the overlying vascular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer

Solid tumors must induce a vascular stroma to grow beyond a minimal size, and the intensity of the angiogenic response has been correlated with prognosis in breast cancer patients. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a secreted protein that has been implicated in tumor-associated angiogenesis. Vascular permeability factor directly stimulates endothelial cell growth and also increases microvascular permeability, leading to the extravasation of plasma proteins, which alter the extracellular matrix in a manner that promotes angiogenesis. To determine whether VPF has a role in breast cancer, we used in situ hybridization to study VPF mRNA expression in normal breast tissue (13 specimens), comedo-type ductal carcinoma in situ (DCIS) (four specimens), infiltrating ductal carcinoma (12 specimens), infiltrating lobular carcinoma (two specimens), metastatic ductal carcinoma (three specimens) and metastatic lobular carcinoma (one specimen). Vascular permeability factor mRNA was expressed at a low level by normal duct epithelium but was expressed at high levels in tumor cells in all cases of comedo-type DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, VPF mRNA was not expressed at high levels in infiltrating lobular carcinoma. We also used in situ hybridization to study the expression of two recently described endothelial cell surface VPF receptors, flt-1 and kdr. Vascular permeability factor receptor mRNA was strongly expressed in endothelial cells of small vessels adjacent to malignant tumor cells in DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, no definite labeling for receptor mRNA was detected in infiltrating lobular carcinoma or nonmalignant breast tissue. The intense expression of VPF mRNA by breast carcinoma cells and of VPF receptor mRNA by endothelial cells of adjacent small blood vessels provides strong evidence linking VPF expression to the angiogenesis associated with comedo-type DCIS, infiltrating ductal, and metastatic ductal breast carcinoma.

Expression of vascular permeability factor (vascular endothelial growth factor) by human corpus luteal cells: Possible role in corpus luteum development

The purpose of conducting cardiovascular safety pharmacology studies is to investigate the pharmacological profiles of new molecular entities (NMEs) and provide data that can be used for optimization of a possible new drug, and help make a selection of NMEs for clinical development. An anaesthetised dog preparation has been used for more than two decades by our department to measure multiple cardiovascular and respiratory parameters and to evaluate different scientific models, leading to more in-depth evaluation of drug-induced cardiovascular effects.An anaesthetic regime developed in house (induction with lofentanil, scopolamine and succinylcholine, and maintenance with fentanyl and etomidate) gives us a preparation free of pain and stress, with minimal effects on the cardiovascular system. This anaesthetic regime had minimal influences on circulating catecholamine levels, on the baroreflex sensitivity, and on all measured basal parameters compared to conscious dogs. All parameters were stable for at least 3 h, with acceptable tolerance intervals, evaluated over 99 safety studies with 3 vehicle treatments (saline, 10% and 20% hydroxypropyl-beta-cyclodextrin). This translates into a highly sensitive model for detecting possible drug-induced effects of NMEs with different mechanisms of action such as: Ca-, Na-, IKr-, IKs-channel blockers, K- and Ca-channel activators, α1- and β-agonists, and muscarinic antagonists. Fentanyl in combination with etomidate is a successful anaesthetic regime in humans [Stockham, R.J., Stanley, T.H., Pace, N.L., King, K., Groen, F. & Gillmor, S.T. (1987). Induction of anaesthesia with fentanyl or fentanyl plus etomidate in high-risk patients. Journal of Cardiothoracic Anesthesia. 1(1), 19–23.]. In the anaesthetised dog, QT correction factors (Van de Water correction and body temperature correction) and risk factors (total, short-term and long-term instability) have been evaluated, using this regime [Van de Water, A., Verheyen, J., Xhonneux, R. & Reneman, R. (1989). An improved method to correct the QT interval of the electrocardiogram for changes in heart rate. Journal of Pharmacological Methods, 22, 207–217.; van der Linde, H.J., Van Deuren, B., Teisman, A., Towart, R. & Gallacher, D.J. (2008). The effect of changes in core body temperature on the QT interval in beagle dogs: A previously ignored phenomenon, with a method for correction. British Journal of Pharmacology, 154, 1474–1481.; van der Linde, H.J., Van de Water, A., Loots, W., Van Deuren, B., Lu, H.R., Van Ammel, K., et al. (2005) A new method to calculate the beat-to-beat instability of QT duration in drug-induced long QT in anaesthetised dogs. Journal of Pharmacological and Toxicological Methods, 52, 168–177.]. Furthermore, this anaesthetic protocol has been used to create different scientific models (long QT, short QT) with different specific end-points (ventricular fibrillation, adrenergic- or pause-dependent TdP) and also their specific precursors: e.g. aftercontractions, phase 2 EADs, phase 3 EADs, DADs, T-wave morphology changes, T-wave alternans, R-on-T, transmural and interventricular dispersion [Gallacher, D.J., Van de Water, A., van der Linde, H.J., Hermans, A.N., Lu, H.R., Towart, R., et al. (2007). In vivo mechanisms precipitating torsade de pointes in canine model of drug-induced long QT1 syndrome. Cardiovascular Research, 76–2, 247–256.]. This paper gives a brief overview of the stability, reproducibility, sensitivity and utility of a well-validated anaesthetised dog model.

Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues.

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a approximately 43-kDa secreted protein that has been shown in bioassays to induce endothelial proliferation, angiogenesis, and capillary hyperpermeability. VPF has been suggested to play an important role in the physiology of normal vasculature. To further elucidate the natural functions of VPF in vivo, the expression of VPF in normal tissues was examined using Northern blot analysis and in situ hybridization histochemistry. VPF mRNA is expressed in the brain, kidney, liver, lung, and spleen of the healthy adult rat. On Northern blots, the relative abundance of VPF mRNA observed in these tissues was highest in the lung and lowest in the spleen. As determined by in situ hybridization, the patterns of VPF expression are organ specific. Hybridization of an antisense VPF probe was concentrated in the cerebellar granule cell layer of the brain and in the glomeruli and tubules of the kidney. In the liver and lung, intense hybridization was observed homogeneously throughout both tissues, demonstrating that VPF mRNA is present in virtually every hepatocyte and pulmonary alveolar cell. Hybridization to the spleen was weaker and more diffuse. The widespread expression and organ-specific distribution of VPF mRNA in normal rat tissues supports the suggestion of an extensive role for this factor in the physiology of normal vasculature.