Abstract 16704: Alterations in Metabolism of Bone Marrow-Derived Mononuclear Cells of Patients With Chronic Heart Failure: Implications for Cell Functionality
Modulation of energy metabolism allows cells to match the divergent demands of the environment. Recent evidence implicates nutrient-responsive metabolites as mediators of crosstalk between metabolic flux, cellular signaling, and epigenetic control of cellular functions. Bone marrow-derived mononuclear cells (BMC) increase the recovery after myocardial ischemia, however, the functional capacity of BMC isolated from patients (pts) with chronic heart failure (CHF) is significantly impaired. Therefore, we examined the regulation of energy metabolism in CHF pt-derived BMC.
BMC isolated of 5 pts with CHF and 10 healthy controls (HC) were functionally characterized by measuring SDF-1-induced invasion, as well as colony forming unit (CFU) capacity. Moreover, the cellular metabolism was analyzed real-time by the Seahorse Bioscience Extracellular Flux Analyzer XF96. We calculated the oxygen consumption rate (OCR) as surrogate for mitochondrial respiration and the extracellular acidification rate (ECAR) for glycolytic capacity. Basal as well as maximal glycolysis was reduced by 5±32% and 38±23% in BMC of CHF patients compared to HC. Importantly, basal as well as maximal respiration were profoundly reduced in BMC derived from CHF pts (72±8%, p=0.03 and 86±10% p=ns of HC, respectively) compared to HC. Interestingly, consistent with a metabolic activation of the bone marrow after acute myocardial infarction (AMI), BMC derived from AMI-pts (n=7) showed an increased glycolytic (154±29%), and slightly increased respiratory (110±7%) capacity compared to CHF-patients. Moreover, basal respiration correlates with the invasion (r=0.662, p=0.01) and CFU capacity (r=0.4525, p=0.035) indicating an influence of metabolism on cell functionality.
Our preliminary data provide first evidence that cardiovascular diseases may induce a specific metabolic alteration in BMC that might influence their functionality and might be responsible for the functional impairment of pt-derived BMC. Future studies will address whether modifying metabolism regulating pathways - particularly increasing mitochondrial respiration- might be a new therapeutic option to improve cell functionality prior to cell therapy.
- © 2013 by American Heart Association, Inc.