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Updated: Oct 4, 2025
Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Targeting ACSL1 promotes cardiomyocyte proliferation and cardiac regeneration
Yuanlong Li1, Ming Yang1, Jing Tan1
1Institute of Guangdong Engineering & Technology Research Center for Disease-Model Animals, Laboratory Animal Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China.
Insights
Neonatal hearts regenerate well, but this capacity declines after postnatal day 7 (P7). Acyl CoA synthase long chain family member 1 (ACSL1) inhibition enhances cardiac regeneration and improves heart function after myocardial infarction in adult mice.
Area of Science:
- Cardiovascular Biology
- Molecular Metabolism
- Regenerative Medicine
Background:
- Neonatal hearts possess significant regenerative potential up to postnatal day 7 (P7).
- Cardiac regeneration capacity diminishes significantly after P7, coinciding with increased lipid metabolism.
- Acyl CoA synthase long chain family member 1 (ACSL1) is a key regulator of lipid metabolism.
Purpose of the Study:
- To investigate the role of ACSL1 in cardiomyocyte regeneration.
- To determine if ACSL1 influences the age-dependent decline in cardiac regenerative capacity.
Main Methods:
- RNA-sequencing of mouse hearts at various developmental stages (E10.5 to 60 days).
- Adeno-associated virus (AAV9) mediated knockdown of ACSL1 in vivo and in primary cardiomyocytes.
- Assessment of cell cycle progression, AKT/FOXO1 signaling, cardiac function, and myocardial regeneration in ACSL1 knockdown models.
Main Results:
- ACSL1 expression significantly increases after P7, correlating with decreased myocardial regeneration.
- Knockdown of ACSL1 enhanced myocardial regeneration in both mouse models and primary cardiomyocytes.
- ACSL1 knockdown promoted cardiomyocyte cell cycle progression and restored cardiac function post-myocardial infarction (MI).
Conclusions:
- ACSL1 plays a critical role in the loss of myocardial regenerative potential after P7.
- Inhibiting ACSL1 promotes cardiac repair and functional recovery following MI in adult mice.
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.
