Intravenous infusion of recombinant human platelet-derived growth factor AB (rhPDGF-AB) in a porcine model of myocardial infarction (MI) promotes cardiac wound healing, improves cardiac function and increases early survival. These findings, published in Science Translational Medicine, indicate a strong translational potential for rhPDGF-AB as an adjunct to current MI therapy.

Systemic infusion of rhPDGF-AB into a murine model of MI has previously been shown to improve cardiac function, which was associated with increased activation of fibroblasts. To extend these findings, James Chong and colleagues sought to determine whether rhPDGF-AB administered during the acute phase of wound healing after MI would modulate scar matrix remodelling. “We were keen to study these findings in a more clinically relevant animal model and, therefore, went on to the pig studies,” explains Chong.

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V. Summersby/Springer Nature Limited

A total of 36 pigs were included in the study and assigned to undergo a sham procedure (n = 5) or MI induced by angioplasty balloon inflation (n = 22). The pigs undergoing MI were further assigned in a 1:1 ratio to receive systemic rhPDGF-AB infusion or sterile water (vehicle) for 7 days via an osmotic mini-pump. Baseline measurements of infarct size (assessed by late gadolinium enhancement) and left ventricular ejection fraction (LVEF) were similar between both treatment groups. However, by day 28, rhPDGF-AB-treated animals had an absolute increase in LVEF from baseline of 11.5 ± 3.3% compared with a decrease of 3.5 ± 1.5% in the vehicle-treated pigs. Furthermore, several indices of myocardial contractility including left ventricular end-systolic volume and the maximal rate of pressure change during systole all demonstrated improved cardiac contractility with rhPDGF-AB treatment.

In addition to functional improvements, rhPDGF-AB infusion was also associated with increased arteriogenesis and arteriolar branching, suggestive of increased de novo formation of microvessels. Surprisingly, rhPDGF-AB treatment did not reduce overall infarct scar size, but the collagen fibres in the scars of rhPDGF-AB-infused pigs were more aligned than those in the vehicle controls, signifying increased scar anisotropy, a conformation that has been associated with improved tissue mechanics. Finally, rhPDGF-AB treatment reduced early death associated with ventricular arrhythmias, possibly through decreased heterogeneity of post-infarct scar composition.

These findings … indicate a strong translational potential for rhPDGF-AB as an adjunct to current MI therapy

“One of the more important aspects of our findings is that the scar collagen matrix can be significantly modulated after MI,” highlights Chong. “This observation has important potential implications for the development of future cardiac therapies.” Chong and colleagues plan to perform more safety-focused experiments before progressing their work towards early-phase clinical testing.