Key result
LVAD unloading linked to adult human cardiomyocyte proliferation and up to ~60% less mitochondrial content.
Why the study?
It was unknown whether mechanical load contributes to postnatal cardiomyocyte cell cycle arrest through mitochondrial content increase and DNA damage response activation.
Does mechanical unloading via LVAD induce cardiomyocyte proliferation and alter mitochondrial content and DNA damage response in patients with advanced heart failure?
Population
10 matched left ventricular samples at LVAD implantation and explantation
Comparison
Post-LVAD explantation vs pre-LVAD implantation
Design
Matched paired tissue analysis
Authors
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Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“We looked at markers of what is called the DNA damage response in cardiomyocytes (heart-muscle cells) of these patients. The response is composed of a cascade of proteins that is activated in response to DNA damage and in turn shuts off the ability of cardiomyocytes to divide. We found that patients who were on LVAD for more than six months had significantly decreased levels of DNA damage response.”
“The report by Canseco et al. might represent a paradigm shift, defined by Thomas Kuhn as 'a change in the basic assumptions, or paradigms, within the ruling theory of science.' The authors present evidence of an increased rate of myocardial cell division in paired myocardial samples after different periods of unloading using LVADs, documented by direct and indirect methods. This was accompanied by decreased numbers of mitochondria and oxidative stress, with a resultant decrease in the DNA damage response.”
“Putting in a mechanical pump rests the heart and apparently sends a signal to make new heart cells. This is the first time that this phenomenon has been shown to occur in human heart failure.”
Prolonged mechanical unloading of the failing human heart induces adult cardiomyocyte proliferation, potentially by preventing mitochondria-mediated activation of the DNA damage response.
Observational (n=10)
No
Does mechanical unloading via LVAD induce cardiomyocyte proliferation and alter mitochondrial content and DNA damage response in patients with advanced heart failure?
Canseco et al. (2015) conducted an observational in Advanced heart failure (n=10). Left ventricular assist device (LVAD) mechanical unloading vs. Pre-LVAD matched tissue samples was evaluated on Mitochondrial content, DNA damage response, and cardiomyocyte proliferation. Mechanical unloading via LVAD induced adult human cardiomyocyte proliferation, decreased mitochondrial content by up to 60%, and reduced cardiomyocyte size by up to 45% compared to pre-LVAD hearts.
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