Mitochondrial function is abnormal in circulating blood monocytes of patients with chronic heart failure

Abstract

Abstract Background Cardiac mitochondrial function is abnormal in heart failure (HF) and is likely to contribute to disease progression. We previously showed that in dogs with HF mitochondrial functional abnormalities exist in both failing cardiomyocytes and in circulating blood monocytes, and to similar extent. This finding suggested the possibility that mitochondrial function in circulating monocytes can serve as a surrogate for cardiac mitochondrial function. We also showed that mitochondrial abnormalities exist in cardiomyocytes of patients with chronic HF. Purpose In the present study we sought to test the difference between patients with advanced HF and age-matched controls in terms of circulating monocyte mitochondrial function. Methods We examined circulating blood monocytes from 10 patients evaluated in our advanced HF clinic and with left ventricular ejection fraction <35%. compared to 10 age-matched control persons without cardiac disease (CON). Peripheral blood samples (15 ml) were obtained from each participant and monocytes were isolated using standard Ficoll-Paque gradient centrifugation. Isolated monocytes were suspended in Agilent XF-DMEM base buffer for quantification of mitochondrial function with Seahorse XFe96 analyzer. The following key mitochondrial functional parameters were determined: basal respiration (BASEresp), ATP production-linked respiration (ATPresp), maximal respiration (MAXresp) and respiratory capacity (RC). Results BASEresp, ATPresp, MAXresp and RC were significantly lower in monocytes of patients with HF compared to NL subjects (BASEresp 2.7 ± 0.7 vs. 5.2 ± 1.6, p<0.05; ATPresp 10.0 ± 0.8 vs. 15.9 ± 1.0, p<0.05; MAXresp 36.5 ± 5.9 vs. 69.3 ± 3.8, p<0.05; RC 26.5 ± 5.5 vs. 53.5 ± 3.5, p<0.05). Conclusions Mitochondrial dysfunction is present in circulating blood monocytes of patients with chronic HF. These findings coupled to those in dogs with HF suggest the possibility that determination of mitochondrial function in peripheral monocytes may identify those patients with HF with cardiac energetic deficiencies. If validated this technique could help illuminate how cardiac energy deprivation relates to disease progression and potentially enable targeted therapies directed at mitochondria dysfunction.