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Long-term LVAD use induced adult cardiomyocyte proliferation
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Prolonged use of left ventricular assist devices by patients with HF may help with regeneration of adult heart muscle.
New data suggest that “the reverse remodeling that occurs with unloading may represent a switch from hypertrophic to hyperplastic growth,” Hesham A. Sadek, MD, PhD, and colleagues wrote.
Adult human cardiomyocytes cannot divide, so adult hearts are not capable of regeneration after substantial cardiomyocyte loss, according to the study background. Previous research established that mitochondria-mediated oxidative DNA damage played a role in postnatal cardiomyocyte cell cycle arrest.
Sadek and colleagues conducted a study to investigate whether mechanical load also plays a role, and hypothesized that physiological increase in mechanical load contributes to the increase in mitochondrial content with subsequent activation of DNA damage response and permanent cell cycle arrest of cardiomyocytes.
The researchers examined the effect of human ventricular unloading after implantation of LVADs on mitochondrial content, DNA damage response and cardiomyocyte proliferation. They examined pre-LVAD and post-LVAD samples of heart muscle in 10 patients with HF (mean age, 51 years; 30% women), who were stratified by LVAD duration (>6 months or <6 months).
Compared with pre-LVAD heart tissues, post-LVAD heart tissues showed up to a 60% decrease in mitochondrial content and up to a 45% decrease in cardiomyocyte size, the researchers found.
Patients who were maintained on LVADs for longer than 6 months had a greater decrease in mitochondrial DNA content compared with LVADs for less than 6 months (shorter group, P = .043; longer group, P = .028). In addition, only those with LVADs for longer than 6 months exhibited a significant decrease in cardiomyocyte size (shorter group, P = .411; longer group, P = .042). The impact on cardiomyocyte size suggests that “ventricular unloading can reverse cardiomyocyte hypertrophy in the human heart,” the researchers wrote.
Cardiomyocytes from patients with LVADs for longer than 6 months also showed a significant decrease in the number of nuclear phosphroylated ataxia telangiectasia mutated protein foci (P=.025), “indicating that the [DNA damage response] is deactivated after prolonged ventricular unloading,” the researchers wrote.
When the researchers examined cardiomyocyte mitosis and cytokinesis, they found a significant increase in phosphorylated histone H3-positive and Aurora B-positive cardiomyocytes in the post-LVAD heart samples, with the greatest increases present in those with LVADs for longer than 6 months.
“This result shows that patients with mechanical assist devices have the ability to make their muscle cells divide,” Sadek, assistant professor of internal medicine at University of Texas Southwestern Medical Center, Dallas, said in a press release. “And the obvious question now is, ‘Are these hearts regenerating? Could LVADs be used as a cure for [HF]’?”
Disclosure: The researchers report no relevant financial disclosures.
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