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1

In vitro and in vivo study of the expression vector encoding vascular endothelial growth factor

100%
Malecki M., Przybyszewska M., Janik P.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 3
243-246
EN
Vascular endothelial growth factor (VEGF) is an angiogenic cytokine with potential therapeutic applications in human diseases. It is a mitogen primarily for endothelial cells. The transfer of the cDNA encoding VEGF to ischemic tissues, which cannot be revascularized otherwise, represents a novel and promising approach to the treatment of vascular disorders. In this work the VEGF165 cDNA was cloned into the expression vector pSecTag2B. The activity of the construct was studied in cell culture as well as in vivo. Western blotting study showed that the cells transfected with the vector secreted significantly higher amounts of VEGF to the culture medium than the non-transfected cells. In vivo study revealed an increased number of new vessels in animals injected with vector encoding VEGF as compared with empty plasmid. Also, tumor cells transfected with the VEGF plasmid exhibited extensive vascularization.
2

The role of angiogenesis in rheumatoid arthritis

100%
Pa?gan K.
Postępy Higieny i Medycyny Doświadczalnej
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2000
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vol. 54
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issue 6
855-865
EN
The paper presents recent data on the angiogenesis and the angiogenic and angiostatic mediators in rheumatoid arthritis
3
Content available remote

New vessel formation after surgical brain injury in the rat?s cerebral cortex. II. Formation of the blood vessels distal to the surgical injury

80%
Walski M., Frontczak-Baniewicz M.
Acta Neurobiologiae Experimentalis
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2003
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vol. 63
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issue 2
77-82
EN
We investigated the features of newly formed blood vessels after surgical brain injury of the rat?s cerebral cortex distal to the operated region. We document the process of split mature blood vessels by an endothelial bridge and morphological features of newly formed vessels. We did not observe a disruption of brain parenchyma. The endothelial lining in vessels was complete. The morphological features of the endothelial cells and basement membrane show that non-sprouting angiogenesis takes place distally to the surgical injury.
4

Endothelial progenitor cells as a new agent contributing to vascular repair

80%
Miller-Kasprzak E., Jagodzinski P. P.
Archivum Immunologiae et Therapiae Experimentalis
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2007
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vol. 55
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issue 4
247-259
EN
A special type of stem cells, defined as endothelial progenitor cells (EPCs), has been found in the bone marrow and peripheral blood. These EPCs are incorporated into injured vessels and become mature endothelial cells during re-endothelialization and neovascularization processes. Though a complete phenotypic description of EPCs remains unclear, these cells express several surface markers, the most relevant including CD34 and CD133 antigens. Furthermore, EPCs derived from other sources could also give rise to mature endothelial cells, which makes this group of cells more diverse. The recruitment of EPCs from the bone marrow to homing sites of vasculogenesis is subject to regulation by many factors, including chemokines and growth factors. The precise mechanism of EPC mobilization and differentiation is not entirely elucidated and is still under investigation. Recent studies have suggested that EPCs may promote local angiogenesis by secreting angiogenic growth factors in a paracrine manner. The number and function of EPCs can be affected during pathological conditions, including diabetes mellitus, cardiovascular risk factors for ischemic disease, and graft vasculopathy. Additionally, EPC number and migration capacity could be improved by such factors as drugs, physical exercise, and growth factors. Transplantation of EPCs into ischemic tissues may emerge as a promising approach in the therapy of diseases associated with blood vessel disorders.
5
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Expression of Angiopoietin-1 and the receptor Tie-2 mRNA in rat brains following intracerebral hemorrhage

80%
Zhou H. J., Tang T., Guo C., Zhang H. N., Zhong J. H., Zheng J., Luo J. K., Lin Y., Liu W., Luo W. F., Yang Q. D.
Acta Neurobiologiae Experimentalis
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2008
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vol. 68
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issue 2
147-154
EN
Angiopoietin-1 (Ang-1) belongs to a novel family of endothelial growth factors that function as ligands for an endothelialspecific receptor tyrosine kinase (Tie-2). The Ang-1/Tie-2 system may contribute to angiogenesis and vascular remodeling by mediating interactions of endothelial cells with smooth muscle cells and pericytes. The spatial distribution and temporal expression of Ang-1 and Tie-2 in the rat brain were studied following collagenase-induced intracerebral hemorrhage (ICH), by immunohistochemistry and reverse transcription-polymerase chain (RT-PCR) analysis, respectively. Immunohistochemical analysis revealed that some Ang-1 or Tie-2-positive dilated vessels resided around the hematoma and extended into the clot. RT-PCR analysis showed that Ang-1 and Tie-2 mRNA signal was detected at 2 days and persisted for 28 days after ICH. These findings suggest that ICH could lead to upregulation of Ang-1 and the receptor Tie-2 mRNA.
6

Gene therapy of cardiovascular diseases

80%
Dulak J.
Biotechnologia
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2000
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issue 1
135-146
EN
Gene therapy is suggested to be beneficial for the treatment of diseases which are difficult or impossible to be cured by classical pharmacotherapy. Thus, the transfer of genetic material of potential therapeutic properties may be particularly helpful in the treatment of hereditary genetic disorders and cancer. However, serious technical obstacles, especially the lack of efficient vectors for the delivery of therapeutic genes have so far prevented the achievement of convincing therapeutic effects. On the other hand, the complications of atherosclerosis, such as heart or peripheral ischaemia, seem to be good candidates for genetic strategies aimed particularly at stimulation of angiogenesis. As in this case therapeutic genes should be expressed locally and in a short time there is a good chance that the application of this therapy will take place earlier than in the case of other disorders. In this paper the first gene therapy clinical trials in human cardiovascular diseases are described. The latest investigations on the basic mechanisms of the blood vessel wall physiology and relationships between factors involved in angiogenesis are also briefly mentioned.
7

The biology and pathology of hypoxia-ischemia: an update

80%
Clarkson A. N., Sutherland B. A., Appleton I.
Archivum Immunologiae et Therapiae Experimentalis
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2005
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vol. 53
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issue 3
213-225
EN
After an hypoxic-ischemic (HI) insult, a multi-faceted complex cascade of events occurs that ultimately causes cell death and neurological damage to the central nervous system. The various cascades include, amongst others: immunological changes, such as the activation of the complement system and the generation of antibodies; increased inflammation through the actions of pro-inflammatory cytokines and chemokines; the production of reactive oxygen species leading to oxidative stress; and diminished mitochondrial function leading to the activation of apoptotic pathways and subsequent alteration in the function of neurons within the contralateral hemisphere. This review addresses the immunological aspects following HI, the role of various cytokines (both pro-inflammatory and anti-inflammatory) and chemokines after the induction of HI. In addition, the role of free radicals in producing HI-induced neurodegeneration and the contribution that mitochondrial dysfunction has in neuronal apoptotic cell death will be discussed. This review also covers the changes that the previously assumed 'internal control', the contralateral hemisphere, undergoes due to HI and describes the difficulties associated with therapy intended to prevent neuronal injury associated with HI.
8

Construction of plasmid bicistronic vectors and their application for in vitro transfection

80%
Kucharzewska F., Zagorska A., Leja J., Jazwa A., Gozdecka M., Jozkowicz A., Dulak J.
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issue 3
66-81
EN
Internal ribosome entry site (IRES) sequences, which stand for the basic element of cap 5'-independent translation, are currently widely used to coexpress heterologous genes from one plasmid. In this study construction of four bicistronic plasmids containing IRES and application of these vectors for transfection of in vitro cultured cells were described. The obtained data show that constructed bicistronic plasmids are very efficient in vitro in terms of simultaneous expression of fibroblast growth factor-4 (FGF-4) and vascular endothelial growth factor (VEGF) or one of these factors and green fluorescent protein (GFP) from one plasmid. Interestingly, expression of two genes, although simultaneous, is not equal. It has turned out that IRES-dependent mRNA translation is less efficient than cap 5'-dependent translation of the first gene, which should be taken into account during construction of bicistronic plasmids.
9

Malformations of angiogenesis in the low differentiated human carcinomas. Immunohistochemical study

80%
Zoltowska A., Stepinski J., Lewko B., Zamorska B., Roszkiewicz A., Serkies K., Kruszewski W.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 1
59-62
EN
Our previous observations showed that the perivascular mesenchyma of the thin-walled vessels (capillaries) in cancers may be the source of organ-specific stem cells. We suggested that the cells forming vascular channels in altered stroma participate in the tumor development. This study was designed to examine the distribution of the vessels and their appearance in the breast, lung and colon cancers. Using immunohistochemical methods, we have shown that in the low differentiated tumors both CD31 and factor VIII antigens may be expressed in capillaries chiefly on the periphery of neoplastic foci. Many of these vessels were discontinuous, with interruptions or unformed tubules. Sporadically, CD31 protein and factor VIII antigens were not expressed in capillaries inside the very low differentiated cancer cases. It is difficult to assess by immunohistochemichal means whether the vascular malformations are the primary or secondary phenomena in the malignancy and why these abnormalities were especially visible in some low differentiated cancers.
10

Molecular addresses of tumors: selection by in vivo phage display

80%
Li X.-B., Schluesener H. J., Xu S. Q.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
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issue 3
177-181
EN
In vivo phage display has been used extensively to screen for novel targets of tumor therapy. Phage display peptide libraries can express random peptides or protein fragments and the aim of phage display is to identify peptide molecules that bind stably to a given target. Angiogenesis is essential to tumor development. Both blood and lymphatic vessels of tumors are different from those of normal tissues. Phage display has been used to analyze the structure and molecular diversity of tumor vasculature and to select tumor-specific antigens which have revealed stage- and type-specific markers of tumor blood vessels. Furthermore, peptides identified by in vivo phage display also work as vehicles to transport cargo therapeutic reagents to tumors. These peptides and their corresponding cellular proteins and ligands may provide molecular tools to selectively target the addresses of tumors and their pathological blood vessels and might increase the efficacy of therapy while decreasing side effects.
11
Content available remote

New vessel formation after surgical brain injury in the rat?s cerebral cortex. I. Formation of the blood vessels proximally to the surgical injury

80%
Frontczak-Baniewicz M., Walski M.
Acta Neurobiologiae Experimentalis
|
2003
|
vol. 63
|
issue 2
65-75
EN
Postnatal neovascularization has been previously considered synonymous with angiogenesis but it was found that circulating endothelial progenitor cells may home into sites of neovascularization and their differentiation into endothelial cells is consistent with vasculogenesis. In this study, we investigated neovascularization of the adult rat?s cerebral cortex after surgical brain injury by electron microscopic ultrastructural and immunocytochemical studies. We found places with disrupted brain parenchyma. The blood vessels showed an incomplete endothelial lining. In the brain parenchyma, we observed fibrin likely derived from disrupted blood vessels. In the plasma there were cell aggregates characterized by endothelial-like features with fibrils in the cytoplasm, untypical for endothelial cells. These endothelial-like cells participated in the process of new vessel formation. We used the anti-alphaV beta3 integrin antibody to visualize the different morphogenic stages of newly formed blood vessels. We demonstrated the relationship between alphaV beta3 integrin localization and different stages of new vessel formation. Our data suggest that growth and development of new blood vessels due to neovascularization following trauma of the adult rat brain are not restricted to angiogenesis but encompass vasculogenesis as well.
12

Therapeutic potential of heme oxygenase-1 in cardiovascular disease

70%
Jazwa A., Florczyk U., Stepniewski J., Jozkowicz A., Dulak J.
Biotechnologia
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2011
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issue 2
166-179
EN
Heme oxygenase-1 (HO1) degrades heme to carbon monoxide (CO), biliverdin, and ferrous iron. Through these products, HO1 mitigates cellular injury by exerting anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Several lines of evidence indicate that angiogenic factors, such as vascular endothelial growth factor A (VEGF) and stromal cell-derived factor 1 (SDF1), mediate their proangiogenic action in endothelial cells and endothelial progenitor cells through induction of HO1, and reciprocally, VEGF and SDF1 are enhanced by HO1 overexpression. Ferrous iron released during the breakdown of free heme by HO1 is an extremely pro-oxidative molecule that can be rapidly removed by ferritin. Of note, this iron sequestering protein also has been shown to exert some proangiogenic effects. Moreover, our recent data indicate that HO1 is an important mediator of differentiation and function of stem cells, including endothelial and myoblasts progenitors. All of this makes HO1 a promising target for novel cardiovascular therapies. The aim of this review is to discuss the existing knowledge and to propose the therapeutic approaches, which have to consider the necessity of tight regulation of HO1 expression.
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