KFU. Card publication. Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors

KAZAN
FEDERAL UNIVERSITY

- RUS
- 中文
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PROANGIOGENIC EFFECT OF 2A-PEPTIDE BASED MULTICISTRONIC RECOMBINANT CONSTRUCTS ENCODING VEGF AND FGF2 GROWTH FACTORS

Form of presentation

Articles in international journals and collections

Year of publication

2021

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Authors, employees of KFU

Kiyasov Andrey Pavlovich, author

Bibliographic description in the original language

Gatina DZ, Garanina EE, Zhuravleva MN, Synbulatova GE, Mullakhmetova AF, Solovyeva VV, Kiyasov AP, Rutland CS, Rizvanov AA, Salafutdinov II. Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors. International Journal of Molecular Sciences. 2021; 22(11):5922. https://doi.org/10.3390/ijms22115922

Annotation

Coronary artery disease remains one of the primary healthcare problems due to the high cost of treatment, increased number of patients, poor clinical outcomes, and lack of effective therapy. Though pharmacological and surgical treatments positively affect symptoms and arrest the disease progression, they generally exhibit a limited effect on the disease outcome. The development of alternative therapeutic approaches towards ischemic disease treatment, especially of decompensated forms, is therefore relevant. Therapeutic angiogenesis, stimulated by various cytokines, chemokines, and growth factors, provides the possibility of restoring functional blood flow in ischemic tissues, thereby ensuring the regeneration of the damaged area. In the current study, based on the clinically approved plasmid vector pVax1, multigenic constructs were developed encoding vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF2), and the DsRed fluorescent protein, integrated via picornaviruses' furin-2A peptide sequences. In vitro experiments demonstrated that genetically modified cells with engineered plasmid constructs expressed the target proteins. Overexpression of VEGF and FGF2 resulted in increased levels of the recombinant proteins. Concomitantly, these did not lead to a significant shift in the general secretory profile of modified HEK293T cells. Simultaneously, the secretome of genetically modified cells showed significant stimulating effects on the formation of capillary-like structures by HUVEC (endothelial cells) in vitro. Our results revealed that when the multicistronic multigene vectors encoding 2A peptide sequences are created, transient transgene co-expression is ensured. The results obtained indicated the mutual synergistic effects of the growth factors VEGF and FGF2 on the proliferation of endothelial cells in vitro. Thus, recombinant multicistronic multigenic constructs might serve as a promising approach for establishing safe and effective systems to treat ischemic diseases.

Keywords

angiogenesis, gene expression, non-viral vectors, 2A-peptides, growth factors, tube formation, VEGF, FGF2, cytokines

The name of the journal

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

URL

https://www.mdpi.com/books/pdfview/book/4832

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=261991&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Kiyasov Andrey Pavlovich	ru_RU
dc.date.accessioned	2021-01-01T00:00:00Z	ru_RU
dc.date.available	2021-01-01T00:00:00Z	ru_RU
dc.date.issued	2021	ru_RU
dc.identifier.citation	Gatina DZ, Garanina EE, Zhuravleva MN, Synbulatova GE, Mullakhmetova AF, Solovyeva VV, Kiyasov AP, Rutland CS, Rizvanov AA, Salafutdinov II. Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors. International Journal of Molecular Sciences. 2021; 22(11):5922. https://doi.org/10.3390/ijms22115922	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=261991&p_lang=2	ru_RU
dc.description.abstract	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES	ru_RU
dc.description.abstract	Coronary artery disease remains one of the primary healthcare problems due to the high cost of treatment, increased number of patients, poor clinical outcomes, and lack of effective therapy. Though pharmacological and surgical treatments positively affect symptoms and arrest the disease progression, they generally exhibit a limited effect on the disease outcome. The development of alternative therapeutic approaches towards ischemic disease treatment, especially of decompensated forms, is therefore relevant. Therapeutic angiogenesis, stimulated by various cytokines, chemokines, and growth factors, provides the possibility of restoring functional blood flow in ischemic tissues, thereby ensuring the regeneration of the damaged area. In the current study, based on the clinically approved plasmid vector pVax1, multigenic constructs were developed encoding vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF2), and the DsRed fluorescent protein, integrated via picornaviruses' furin-2A peptide sequences. In vitro experiments demonstrated that genetically modified cells with engineered plasmid constructs expressed the target proteins. Overexpression of VEGF and FGF2 resulted in increased levels of the recombinant proteins. Concomitantly, these did not lead to a significant shift in the general secretory profile of modified HEK293T cells. Simultaneously, the secretome of genetically modified cells showed significant stimulating effects on the formation of capillary-like structures by HUVEC (endothelial cells) in vitro. Our results revealed that when the multicistronic multigene vectors encoding 2A peptide sequences are created, transient transgene co-expression is ensured. The results obtained indicated the mutual synergistic effects of the growth factors VEGF and FGF2 on the proliferation of endothelial cells in vitro. Thus, recombinant multicistronic multigenic constructs might serve as a promising approach for establishing safe and effective systems to treat ischemic diseases.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	angiogenesis	ru_RU
dc.subject	gene expression	ru_RU
dc.subject	non-viral vectors	ru_RU
dc.subject	2A-peptides	ru_RU
dc.subject	growth factors	ru_RU
dc.subject	tube formation	ru_RU
dc.subject	VEGF	ru_RU
dc.subject	FGF2	ru_RU
dc.subject	cytokines	ru_RU
dc.title	Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors	ru_RU
dc.type	Articles in international journals and collections	ru_RU