Platelet-derived growth factor-AB improves scar mechanics and vascularity after myocardial infarction

Sujitha Thavapalachandran; Stuart M. Grieve; Robert D. Hume; Thi Yen Loan Le; Kalyan Raguram; James E. Hudson; Jim Pouliopoulos; Gemma A. Figtree; Rafael P. Dye; Anthony M. Barry; Paula Brown; Juntang Lu; Sean Coffey; Scott H. Kesteven; Richard J. Mills; Fairooj N. Rashid; Elena Taran; Pramesh Kovoor; Liza Thomas; Alan Robert Denniss; Eddy Kizana; Naisana S. Asli; Munira Xaymardan; Michael P. Feneley; Robert M. Graham; Richard P. Harvey; James J. H. Chong

doi:10.1126/scitranslmed.aay2140

Research ArticleCardiology

Platelet-derived growth factor-AB improves scar mechanics and vascularity after myocardial infarction

View ORCID ProfileSujitha Thavapalachandran ¹,²,
View ORCID ProfileStuart M. Grieve³,
Robert D. Hume¹,
View ORCID ProfileThi Yen Loan Le¹,
View ORCID ProfileKalyan Raguram¹,
James E. Hudson⁴,
Jim Pouliopoulos²,
Gemma A. Figtree⁵,
View ORCID ProfileRafael P. Dye⁵,
View ORCID ProfileAnthony M. Barry²,
Paula Brown²,
Juntang Lu²,
View ORCID ProfileSean Coffey ⁵,⁶,
Scott H. Kesteven⁷,
Richard J. Mills⁴,
Fairooj N. Rashid¹,
View ORCID ProfileElena Taran⁸,⁹,
Pramesh Kovoor²,
Liza Thomas²,
Alan Robert Denniss²,
Eddy Kizana¹,²,
View ORCID ProfileNaisana S. Asli⁷,¹⁰,¹¹,
Munira Xaymardan⁷,
Michael P. Feneley⁷,¹²,
Robert M. Graham⁷,¹²,
View ORCID ProfileRichard P. Harvey⁷,¹²,¹³ and
View ORCID ProfileJames J. H. Chong ¹,²,*

¹Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
²Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.
³Sydney Translational Imaging Laboratory, Heart Research Institute, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.
⁴QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
⁵Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
⁶Department of Medicine, Dunedin School of Medicine, Dunedin Hospital, Dunedin 9016, New Zealand.
⁷Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
⁸Australian National Fabrication Facility–Queensland Node, The University of Queensland, St. Lucia, QLD 4072, Australia.
⁹School of Chemical Engineering, University of Melbourne, VIC 3010, Australia.
¹⁰Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia.
¹¹Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, NSW 2145, Australia.
¹²St. Vincent’s Clinical School, UNSW Sydney, Kensington, NSW 2052, Australia.
¹³School of Biotechnology and Biomolecular Science, UNSW Sydney, Kensington, NSW 2052, Australia.

↵*Corresponding author. Email: james.chong{at}sydney.edu.au

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Science Translational Medicine 01 Jan 2020:
Vol. 12, Issue 524, eaay2140
DOI: 10.1126/scitranslmed.aay2140

Sujitha Thavapalachandran

1Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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Stuart M. Grieve

3Sydney Translational Imaging Laboratory, Heart Research Institute, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.

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Robert D. Hume

1Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.

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Thi Yen Loan Le

1Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.

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Kalyan Raguram

1Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.

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James E. Hudson

4QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.

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Jim Pouliopoulos

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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Gemma A. Figtree

5Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.

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Rafael P. Dye

5Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.

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Anthony M. Barry

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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Paula Brown

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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Juntang Lu

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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Sean Coffey

5Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.

6Department of Medicine, Dunedin School of Medicine, Dunedin Hospital, Dunedin 9016, New Zealand.

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Scott H. Kesteven

7Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.

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Richard J. Mills

4QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.

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Fairooj N. Rashid

1Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.

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Elena Taran

8Australian National Fabrication Facility–Queensland Node, The University of Queensland, St. Lucia, QLD 4072, Australia.

9School of Chemical Engineering, University of Melbourne, VIC 3010, Australia.

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Pramesh Kovoor

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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Liza Thomas

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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Alan Robert Denniss

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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Eddy Kizana

1Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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Naisana S. Asli

7Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.

10Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia.

11Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, NSW 2145, Australia.

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Munira Xaymardan

7Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.

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Michael P. Feneley

7Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.

12St. Vincent’s Clinical School, UNSW Sydney, Kensington, NSW 2052, Australia.

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Robert M. Graham

7Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.

12St. Vincent’s Clinical School, UNSW Sydney, Kensington, NSW 2052, Australia.

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Richard P. Harvey

7Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.

12St. Vincent’s Clinical School, UNSW Sydney, Kensington, NSW 2052, Australia.

13School of Biotechnology and Biomolecular Science, UNSW Sydney, Kensington, NSW 2052, Australia.

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James J. H. Chong

1Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.

2Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.

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For correspondence: james.chong@sydney.edu.au

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Straightening up scars

As a result of myocardial infarction (MI; heart attack), scar tissue forms that negatively affects cardiac function. Thavapalachandran et al. investigated the potential therapeutic effects of intravenous delivery of recombinant human platelet-derived growth factor-AB (rhPDGF-AB) after MI in a randomized, double-blinded study in pigs. Cardiac function was improved 28 days after treatment was initiated and rhPDGF-AB enhanced angiogenesis; however, there was no difference in the size of scars between rhPDGF-AB–treated and vehicle-treated pigs. Scars in rhPDGF-AB–treated pigs showed less heterogeneity and greater fiber alignment, and rhPDGF-AB–treated pigs were less susceptible to arrhythmia after MI. Results support the translational potential of rhPDGF-AB to modulate scars and augment cardiac repair.

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Platelet-derived growth factor-AB improves scar mechanics and vascularity after myocardial infarction

Straightening up scars

Science Translational Medicine

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