Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction

Xiaojin Hao, Eduardo Silva, Agneta Månsson-Broberg, Karl Henrik Grinnemo, Anwar J. Siddiqui, Göran Dellgren, Eva Wärdell, Lars Åke Brodin, David J. Mooney, Christer Sylvén

Research output: Contribution to journalArticle

261 Citations (Scopus)

Abstract

Objective: This study investigates whether local sequential delivery of vascular endothelial growth factor-A165 (VEGF-A165) followed by platelet-derived growth factor-BB (PDGF-BB) with alginate hydrogels could induce an angiogenic effect and functional improvement greater than single factors after myocardial infarction. Methods: Alginate hydrogels were prepared by combining high and low molecular weight alginate. Growth factor release rates were monitored over time in vitro with 125I-labelled VEGF-A165 and PDGF-BB included in the gels. One week after myocardial infarction was induced in Fisher rats, gels with VEGF-A165, PDGF-BB, or both were given intra-myocardially along the border of the myocardial infarction. Vessel density was analysed in hearts and cardiac function was determined by Tissue Doppler Echocardiography. In addition, the angiogenic effect of sequenced delivery was studied in vitro in aortic rings from C57B1/6 mice. Results: Alginate gels were capable of delivering VEGF-A165 and PDGF-BB in a sustainable manner, and PDGF-BB was released more slowly than VEGF-A165. Sequential growth factor administration led to a higher density of α-actin positive vessels than single factors, whereas no further increment was found in capillary density. Sequential protein delivery increased the systolic velocity-time integral and displayed a superior effect than single factors. In the aortic ring model, sequential delivery led to a higher angiogenic effect than single factor administration. Conclusions: The alginate hydrogel is an effective and promising injectable delivery system in a myocardial infarction model. Sequential growth factor delivery of VEGF-A165 and PDGF-BB induces mature vessels and improves cardiac function more than each factor singly. This may indicate clinical utility.

Original languageEnglish (US)
Pages (from-to)178-185
Number of pages8
JournalCardiovascular Research
Volume75
Issue number1
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

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Hydrogels
Vascular Endothelial Growth Factor A
Myocardial Infarction
Intercellular Signaling Peptides and Proteins
Gels
Doppler Echocardiography
Hydrogel
alginic acid
platelet-derived growth factor BB
Actins
Molecular Weight
Injections
Proteins

Keywords

  • Angiogenesis
  • Growth factors
  • Infarction
  • Tissue engineering
  • Ventricular function

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction. / Hao, Xiaojin; Silva, Eduardo; Månsson-Broberg, Agneta; Grinnemo, Karl Henrik; Siddiqui, Anwar J.; Dellgren, Göran; Wärdell, Eva; Brodin, Lars Åke; Mooney, David J.; Sylvén, Christer.

In: Cardiovascular Research, Vol. 75, No. 1, 01.07.2007, p. 178-185.

Research output: Contribution to journalArticle

Hao, X, Silva, E, Månsson-Broberg, A, Grinnemo, KH, Siddiqui, AJ, Dellgren, G, Wärdell, E, Brodin, LÅ, Mooney, DJ & Sylvén, C 2007, 'Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction', Cardiovascular Research, vol. 75, no. 1, pp. 178-185. https://doi.org/10.1016/j.cardiores.2007.03.028
Hao, Xiaojin ; Silva, Eduardo ; Månsson-Broberg, Agneta ; Grinnemo, Karl Henrik ; Siddiqui, Anwar J. ; Dellgren, Göran ; Wärdell, Eva ; Brodin, Lars Åke ; Mooney, David J. ; Sylvén, Christer. / Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction. In: Cardiovascular Research. 2007 ; Vol. 75, No. 1. pp. 178-185.
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T1 - Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction

AU - Hao, Xiaojin

AU - Silva, Eduardo

AU - Månsson-Broberg, Agneta

AU - Grinnemo, Karl Henrik

AU - Siddiqui, Anwar J.

AU - Dellgren, Göran

AU - Wärdell, Eva

AU - Brodin, Lars Åke

AU - Mooney, David J.

AU - Sylvén, Christer

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N2 - Objective: This study investigates whether local sequential delivery of vascular endothelial growth factor-A165 (VEGF-A165) followed by platelet-derived growth factor-BB (PDGF-BB) with alginate hydrogels could induce an angiogenic effect and functional improvement greater than single factors after myocardial infarction. Methods: Alginate hydrogels were prepared by combining high and low molecular weight alginate. Growth factor release rates were monitored over time in vitro with 125I-labelled VEGF-A165 and PDGF-BB included in the gels. One week after myocardial infarction was induced in Fisher rats, gels with VEGF-A165, PDGF-BB, or both were given intra-myocardially along the border of the myocardial infarction. Vessel density was analysed in hearts and cardiac function was determined by Tissue Doppler Echocardiography. In addition, the angiogenic effect of sequenced delivery was studied in vitro in aortic rings from C57B1/6 mice. Results: Alginate gels were capable of delivering VEGF-A165 and PDGF-BB in a sustainable manner, and PDGF-BB was released more slowly than VEGF-A165. Sequential growth factor administration led to a higher density of α-actin positive vessels than single factors, whereas no further increment was found in capillary density. Sequential protein delivery increased the systolic velocity-time integral and displayed a superior effect than single factors. In the aortic ring model, sequential delivery led to a higher angiogenic effect than single factor administration. Conclusions: The alginate hydrogel is an effective and promising injectable delivery system in a myocardial infarction model. Sequential growth factor delivery of VEGF-A165 and PDGF-BB induces mature vessels and improves cardiac function more than each factor singly. This may indicate clinical utility.

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