Thymosin β4 and prothymosin α promote cardiac regeneration post-ischaemic injury in mice

Gladka MM, Johansen AKZ, van Kampen SJ, Peters MMC, Molenaar B, Versteeg D, Kooijman L, Zentilin L, Giacca M, van Rooij E · Cardiovascular Research

The Tβ4-plus-prothymosin-α combination created a permissive environment for cardiomyocyte proliferation and reduced cardiac dysfunction after ischaemic injury — ejection fraction and isovolumic relaxation time recovered, posterior wall thickness did not, and large clusters of mononucleated cardiomyocytes rose from 2.9% to 15.8% of cells in the clonal analysis. An independent group recovering a cardiac benefit, though by gene delivery rather than injected peptide.

Population

Mice after ischaemia-reperfusion cardiac injury, 15 injured and 6 sham per vector

Intervention

Viral overexpression of thymosin β4 together with prothymosin α in the myocardial wall

Comparator

Control vector

Limitations

Overexpression of two genes in combination, not administration of Tβ4 protein; in culture each factor raised cardiomyocyte proliferation on its own, but the in-vivo benefit was tested only for the pair. Funded by Horizon 2020, NWO and ERA-CVD grants and a Dutch Heart Foundation fellowship; no conflict declared.