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

Autor:	Thavapalachandran S; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia., Grieve SM; Sydney Translational Imaging Laboratory, Heart Research Institute, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia., Hume RD; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia., Le TYL; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia., Raguram K; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia., Hudson JE; QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia., Pouliopoulos J; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia., Figtree GA; Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia., Dye RP; Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia., Barry AM; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia., Brown P; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia., Lu J; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia., Coffey S; Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.; Department of Medicine, Dunedin School of Medicine, Dunedin Hospital, Dunedin 9016, New Zealand., Kesteven SH; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia., Mills RJ; QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia., Rashid FN; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia., Taran E; Australian National Fabrication Facility-Queensland Node, The University of Queensland, St. Lucia, QLD 4072, Australia.; School of Chemical Engineering, University of Melbourne, VIC 3010, Australia., Kovoor P; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia., Thomas L; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia., Denniss AR; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia., Kizana E; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia., Asli NS; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.; Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia.; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, NSW 2145, Australia., Xaymardan M; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia., Feneley MP; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.; St. Vincent's Clinical School, UNSW Sydney, Kensington, NSW 2052, Australia., Graham RM; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.; St. Vincent's Clinical School, UNSW Sydney, Kensington, NSW 2052, Australia., Harvey RP; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.; St. Vincent's Clinical School, UNSW Sydney, Kensington, NSW 2052, Australia.; School of Biotechnology and Biomolecular Science, UNSW Sydney, Kensington, NSW 2052, Australia., Chong JJH; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia. james.chong@sydney.edu.au.; Department of Cardiology, Westmead Hospital, Westmead, NSW 2145, Australia.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2020 Jan 01; Vol. 12 (524).
DOI:	10.1126/scitranslmed.aay2140
Abstrakt:	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. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu