Background: Neonatal hearts have considerable regenerative potential within 7 days post birth (P7), but the rate of regeneration is extremely low after P7. Interestingly, lipid metabolism increases dramatically after P7. The similarities in these age profiles suggests a possible link between cardiac regeneration and lipid metabolism. Acyl CoA synthase long chain family member 1 (ACSL1) is the key enzyme that regulates lipid metabolism. The aim of this study was to identify the role of ACSL1 in the regeneration of cardiomyocytes.
Methods And Results: The uptake of fatty acids in hearts increased after P7; however, myocardial regeneration was decreased. We profiled an RNA-sequence array of hearts from mice of different ages, including E10.5 (embryonic stage)-, 3-, 7-, 21-, 30-, and 60-day-old mice, and found that the expression of ACSL1 was significantly increased after P7. By establishing ACSL1 knockdown mice with adeno-associated virus (AAV9). Then, we verified that knockdown of ACSL1 enhanced the capacity for myocardial regeneration both in mice and in primary cardiomyocytes. Indeed, ACSL1 knockdown in primary cardiomyocytes promoted the cell cycle progression from G0 to G2 phase by regulating specific factors, which may correlate with the activation of AKT by ACSL1 and withdrawal of FOXO1 from the nucleus. In vivo, knockdown of ACSL1 effectively restored cardiac function and myocardial regeneration in adult mice with myocardial infarction (MI).
Conclusions: ACSL1 possibly induces the loss of the myocardial regenerative potential beginning at P7 in mice, and inhibition of ACSL1 effectively promoted myocardial repair after MI in mice.
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| http://dx.doi.org/10.1016/j.lfs.2022.120371 | DOI Listing |
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