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Published on: March 30, 2022
Human Hearts Intrinsically Increase Cardiomyocyte Mitosis After Myocardial Infarction
Robert D Hume1,2,3, Jessica Warwick1,2, Woo Jun Shim4
1School of Medical Sciences, Faculty of Medicine and Health (R.D.H., J.W., C.M., L.S., D.H., E.S., X.W., L.N., L.C., A.L.F., M.L., S.L.), University of Sydney, Sydney, New South Wales, Australia.
Insights
Adult human heart cells (cardiomyocytes) can divide after a heart attack (myocardial infarction). This finding offers hope for developing new treatments to regenerate heart tissue and reverse heart failure.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Cardiac Physiology
Background:
- Myocardial infarction (MI) is a major global cause of death, leading to significant loss of cardiomyocytes.
- Cardiomyocytes typically cease cell division after birth, unlike in some animal models where they proliferate post-MI.
- The capacity for human cardiomyocyte mitosis following MI has remained largely uncharacterized.
Purpose of the Study:
- To investigate the potential for cardiomyocyte cell division in adult humans after myocardial infarction.
- To explore the intrinsic regenerative capacity of the human heart post-ischemia.
Main Methods:
- Utilized a unique premortem post-MI human heart sample.
- Employed a combination of techniques including immunostaining, bulk and single-nucleus RNA sequencing, proteomics, and metabolomics.
- Developed and applied a novel post-MI human biopsy method for cardiomyocyte analysis.
Main Results:
- Demonstrated that adult human cardiomyocytes exhibit increased mitosis in response to ischemia.
- Confirmed the occurrence of cytokinesis in human cardiomyocytes following myocardial infarction.
Conclusions:
- Adult human cardiomyocytes possess an intrinsic ability to undergo mitosis and cytokinesis after ischemic injury.
- Therapeutic strategies aimed at enhancing this innate mitotic potential could pave the way for cardiac regeneration and heart failure reversal.
Background:
Myocardial infarction (MI) is a leading cause of death worldwide and can eliminate up to a third of the cardiomyocytes within the human heart. Although cardiomyocytes undergo mitosis during early development, most cardiomyocytes cease cell cycling soon after birth. In contrast, rodent MI models have shown that cardiomyocytes increase mitosis in response to ischemia; however, this has not been shown in humans.
Methods:
Using a unique premortem post-MI human heart, immunostaining, bulk RNA sequencing, proteomics, metabolomics, single-nucleus RNA sequencing and a novel post-MI human biopsy method, we investigated human cardiomyocyte mitosis post-MI.
Results:
We show that adult human cardiomyocytes exhibit increased mitosis and cytokinesis in response to ischemia.
Conclusions:
Future development of therapeutics to enhance this intrinsic mitotic potential could lead to new treatments that reverse heart failure via cardiac regeneration.
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