Nature communicationsNov 24, 2025

Briefly increasing hPKM2 levels in pig heart muscle cells may prevent heart failure after a heart attack

Regenerative Health Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Transient modified mRNA delivery improved post-injury heart repair signals and function in pig models.

Evidence

This preclinical porcine ischemic-injury study tested targeted non-viral modified mRNA in juvenile pigs one week after injury and adult pigs immediately after injury, with follow-up at two months and one month.

Caveat

The work is in pig models with age- and timing-specific treatment windows, so the claimed human heart-failure prevention remains untested clinically.

Simplified

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.

Key numbers

50.3%

Increase in Ejection Fraction

Ejection fraction rose from 31.7% in controls to 50.3% in -treated pigs.

22.5%

Scar Size Reduction

Infarct size decreased by 22.5% in -treated pigs.

2 of 2

CM Proliferation Increase

Both treatments showed increased proliferation in the of the heart.

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Funding

Competing interests

1 author, Lior Zangi, disclosed being an inventor of issued patents titled “Cell-specific expression of modRNA” covering hPKM2 CM SMRTs for cardiac repair after myocardial infarction.

PubMed

Briefly increasing hPKM2 levels in pig heart muscle cells may prevent heart failure after a heart attack

Abstract

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Competing interests

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Abstract

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