Format

Send to

Choose Destination
Sci Transl Med. 2020 Jan 1;12(524). pii: eaay2140. doi: 10.1126/scitranslmed.aay2140.

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

Author information

1
Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
2
Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.
3
Sydney Translational Imaging Laboratory, Heart Research Institute, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.
4
QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
5
Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
6
Department of Medicine, Dunedin School of Medicine, Dunedin Hospital, Dunedin 9016, New Zealand.
7
Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
8
Australian National Fabrication Facility-Queensland Node, The University of Queensland, St. Lucia, QLD 4072, Australia.
9
School of Chemical Engineering, University of Melbourne, VIC 3010, Australia.
10
Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia.
11
Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, NSW 2145, Australia.
12
St. Vincent's Clinical School, UNSW Sydney, Kensington, NSW 2052, Australia.
13
School of Biotechnology and Biomolecular Science, UNSW Sydney, Kensington, NSW 2052, Australia.
14
Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia. james.chong@sydney.edu.au.

Abstract

Therapies that target scar formation after myocardial infarction (MI) could prevent ensuing heart failure or death from ventricular arrhythmias. We have previously shown that recombinant human platelet-derived growth factor-AB (rhPDGF-AB) improves cardiac function in a rodent model of MI. To progress clinical translation, we evaluated rhPDGF-AB treatment in a clinically relevant porcine model of myocardial ischemia-reperfusion. Thirty-six pigs were randomized to sham procedure or balloon occlusion of the proximal left anterior descending coronary artery with 7-day intravenous infusion of rhPDGF-AB or vehicle. One month after MI, rhPDGF-AB improved survival by 40% compared with vehicle, and cardiac magnetic resonance imaging showed left ventricular (LV) ejection fraction improved by 11.5%, driven by reduced LV end-systolic volumes. Pressure volume loop analyses revealed improved myocardial contractility and energetics after rhPDGF-AB treatment with minimal effect on ventricular compliance. rhPDGF-AB enhanced angiogenesis and increased scar anisotropy (high fiber alignment) without affecting overall scar size or stiffness. rhPDGF-AB reduced inducible ventricular tachycardia by decreasing heterogeneity of the ventricular scar that provides a substrate for reentrant circuits. In summary, we demonstrated that rhPDGF-AB promotes post-MI cardiac wound repair by altering the mechanics of the infarct scar, resulting in robust cardiac functional improvement, decreased ventricular arrhythmias, and improved survival. Our findings suggest a strong translational potential for rhPDGF-AB as an adjunct to current MI treatment and possibly to modulate scar in other organs.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center