TY - JOUR
T1 - Transient overexpression of hPKM2 in porcine cardiomyocytes prevents heart failure after myocardial infarction
AU - Sun, Jiacheng
AU - Wu, Yalin
AU - Adjmi, Matthew
AU - Matthews, Rachel C.
AU - Kurian, Ann Anu
AU - Żak, Magdalena M.
AU - Yoo, Jimeen
AU - Mainkar, Gayatri
AU - Lawless, Hannah
AU - Lu, Yu An
AU - Soon-Shiong, Patrick
AU - Walcott, Gregory P.
AU - Sadek, Hesham A.
AU - Zhang, Jianyi
AU - Zangi, Lior
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - The adult mammalian heart lacks the ability to regenerate after injury, contributing to heart failure. No current treatment reactivates heart muscle cell division to prevent this decline. We used a targeted, non-viral modified mRNA system to transiently boost expression of a regenerative enzyme, pyruvate kinase muscle isozyme M2, in heart muscle cells of juvenile and adult pig models after ischemic injury. In juvenile pigs treated one-week post-injury, we observed increased markers of cell division, secretion of protective factors, improved heart function, and reduced scarring two months later. In adult pigs treated immediately after injury, we saw improved heart contractility and less fibrosis one month later. These results show that targeted pyruvate kinase muscle isozyme M2 modified mRNA delivery can stimulate muscle regeneration and functional recovery in both young and adult pig hearts. This approach offers a promising strategy for repairing ischemic injury and preventing heart failure in humans.
AB - The adult mammalian heart lacks the ability to regenerate after injury, contributing to heart failure. No current treatment reactivates heart muscle cell division to prevent this decline. We used a targeted, non-viral modified mRNA system to transiently boost expression of a regenerative enzyme, pyruvate kinase muscle isozyme M2, in heart muscle cells of juvenile and adult pig models after ischemic injury. In juvenile pigs treated one-week post-injury, we observed increased markers of cell division, secretion of protective factors, improved heart function, and reduced scarring two months later. In adult pigs treated immediately after injury, we saw improved heart contractility and less fibrosis one month later. These results show that targeted pyruvate kinase muscle isozyme M2 modified mRNA delivery can stimulate muscle regeneration and functional recovery in both young and adult pig hearts. This approach offers a promising strategy for repairing ischemic injury and preventing heart failure in humans.
UR - https://www.scopus.com/pages/publications/105022743641
U2 - 10.1038/s41467-025-65344-4
DO - 10.1038/s41467-025-65344-4
M3 - Article
C2 - 41285815
AN - SCOPUS:105022743641
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 10354
ER -