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Therapeutic potential of heme oxygenase-1 in cardiovascular disease

100%

Jazwa A., Florczyk U., Stepniewski J., Jozkowicz A., Dulak J.

Biotechnologia

2011

issue 2

166-179

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.

Regulation of gene expression in plasmid vectors: doxocyclin-dependent and hypoxia-regulated systems

73%

Golda S., Kucharzewska P., Cisowski J., Florczyk U., Zagorska A., Jazwa A., Loboda A., Jozkowicz A., Dulak J.

Biotechnologia

2007

issue 3

82-97

Regulation of gene expression in gene therapy is crucial for obtaining the therapeutic effects, thanks to limitation of transgene activity to the selected cells in a given time. In this paper we have focused on plasmid expression systems regulated by doxycycline or hypoxia. We have described in details the structure, regulatory elements and biological applications of 1) the modified, commercially available Tet-On system, expressing doxycycline-controlled b-galactosidase and, 2) hypoxia-activated FGF-4/VEGF expression plasmid containing the hypoxia responsive sequence. The presented expression systems can also be used in viral vectors, enabling not only regulated, but also high and long-term expression of transgenes.

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2 Biotechnologia

1 2011

1 2007

2 Dulak J.

2 Florczyk U.

2 Jazwa A.

2 Jozkowicz A.

1 Cisowski J.

1 Golda S.

1 Kucharzewska P.

1 Loboda A.

1 Stepniewski J.

1 Zagorska A.

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Therapeutic potential of heme oxygenase-1 in cardiovascular disease

Regulation of gene expression in plasmid vectors: doxocyclin-dependent and hypoxia-regulated systems