Rapid induction of vascular endothelial growth factor expression by transient ischemia in rat heart

Vascular endothelial growth factor (VEGF or vascular permeability factor), a direct-acting, endothelial cell-specific mitogen, has been suggested to be involved in development and maintenance of vasculatures in tumor neovascularization and in normal tissues. To investigate possible roles of VEGF in ischemic hearts, we studied induction of VEGF mRNA by ischemia and hypoxia using coronary artery-ligated hearts in vivo and perfused hearts and cultured myocardial cells in vitro. VEGF mRNA was potently induced by ischemia in the heart in vivo. In perfused hearts, maximum expression was rapidly induced (within 30 min) by transient reversible ischemia (5–10 min of ischemia) and lasted at least 3 h. Induction was also caused by hypoxia, which was confirmed in perfused hearts and cultured myocardial cells. These results suggest that induction of VEGF mRNA is upregulated by oxygen deprivation in the heart and that not only infarction but also chronic ischemia in the clinical setting could induce VEGF as a potent angiogenesis factor to stimulate coronary collateral formation.

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Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors.

Molecular Biology of the Cell ◽

10.1091/mbc.3.2.211 ◽

1992 ◽

Vol 3 (2) ◽

pp. 211-220 ◽

Cited By ~ 592

Author(s):

B Berse ◽

L F Brown ◽

L Van de Water ◽

H F Dvorak ◽

D R Senger

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Vascular Permeability ◽

Microvascular Permeability ◽

Northern Analysis ◽

Vascular Endothelial ◽

Vegf Mrna ◽

Vascular Permeability Factor ◽

Permeability Factor ◽

Endothelial Growth Factor

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), increases microvascular permeability and is a specific mitogen for endothelial cells. Expression of VPF/VEGF previously was demonstrated in a variety of tumor cells, in cultures of pituitary-derived cells, and in corpus luteum. Here we present evidence, by Northern analysis and in situ hybridization, that the VPF/VEGF gene is expressed in many adult organs, including lung, kidney, adrenal gland, heart, liver, and stomach mucosa, as well as in elicited peritoneal macrophages. The highest levels of VPF/VEGF transcripts were found in epithelial cells of lung alveoli, renal glomeruli and adrenal cortex, and in cardiac myocytes. The prominence of VPF/VEGF mRNA in these tissues suggests a possible role for VPF/VEGF in regulating baseline microvascular permeability, which is essential for tissue nutrition and waste removal. We also demonstrate particularly high VPF/VEGF mRNA levels in several human tumors, where it may be involved in promoting tumor angiogenesis and stroma generation, both as an endothelial cell mitogen and indirectly by its permeability enhancing effect that leads to the deposition of a provisional fibrin gel matrix.

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Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor

Journal of Cell Science ◽

10.1242/jcs.108.6.2369 ◽

1995 ◽

Vol 108 (6) ◽

pp. 2369-2379 ◽

Cited By ~ 24

Author(s):

W.G. Roberts ◽

G.E. Palade

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Intradermal Injection ◽

Microvascular Permeability ◽

Vascular Endothelial ◽

Vascular Permeability Factor ◽

Fenestrated Endothelium ◽

Vascular Beds ◽

Endothelial Growth Factor

The vascular endothelial growth factor (VEGF) was originally described as vascular permeability factor due to its ability to increase microvascular permeability to plasma proteins. However, the vessel types (arteriolar, venular, and capillary) affected by VEGF and the modification of endothelial morphology in response to increased permeability induced by VEGF in vivo have not been precisely documented. By topical application or intradermal injection of recombinant human VEGF-165 we find that VEGF increases the permeability of postcapillary venules as well as muscular venules and capillaries. Surprisingly, we also find that endothelia of small venules and capillaries become fenestrated within 10 minutes of VEGF application. Fenestrations appeared in vascular beds which do not normally have fenestrated endothelium, namely the cremaster muscle and skin. Histamine, saline, and heat-inactivated VEGF do not cause fenestrations. Increased permeability is completely inhibited when VEGF is cleared by immunoprecipitation with anti-VEGF monoclonal antibodies. The VEGF effect on permeability is unlike that of any other mediator described to date since both muscular venules and capillaries are affected.

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Differential expression and selective localization of vascular permeability factor/vascular endothelial growth factor in the rat uterus during the estrous cycle

Journal of Endocrinology ◽

10.1677/joe.0.1590489 ◽

1998 ◽

Vol 159 (3) ◽

pp. 489-499 ◽

Cited By ~ 31

Author(s):

AR Karuri ◽

AM Kumar ◽

D Mukhopadhyay

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Vascular Permeability ◽

Differential Expression ◽

Estrous Cycle ◽

Vascular Endothelial ◽

Vegf Mrna ◽

Vascular Permeability Factor ◽

Rat Uterus ◽

Endothelial Growth Factor

This study examines the expression of the multi-functional cytokine, vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in the rat uterus during early proestrus, proestrus, estrus and diestrus. Groups of ovariectomized or hypophysectomized rats served as endocrine controls. Expression of VPF/VEGF mRNA was 2-fold greater in uteri during proestrus and estrus than in other phases of the estrous cycle. In situ hybridization techniques indicated that VPF/VEGF mRNA expression was confined to the luminal epithelium during proestrus, but shifted to the stromal compartment during estrus. Ovariectomized, hypophysectomized or diestrus rats exhibited scattered localization of VPF/VEGF mRNA among glandular epithelium and endometrial stromal compartments. Although VPF/VEGF mRNA was expressed throughout the estrous cycle, but in different compartments of the endometrium depending on the stage of the estrous cycle, VPF/VEGF protein expression appears to be restricted to the epithelial compartment during proestrus and estrus. Results indicate that circulating levels of gonadal steroids and LH may be associated with the differential expression of VPF/VEGF mRNA and its translation activity in the endometrium during different stages of the estrous cycle.

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