The labile iron pool in monocytes reflects the activity of the atherosclerotic process in men with chronic cardiovascular disease.

The study investigates the relationship between the labile iron pool (LIP) in circulating monocytes and markers of iron metabolism, inflammation, oxidative stress, endothelial dysfunction and arterial elasticity in patients with chronic cardiovascular disease and in healthy volunteers. The patients with a history of CVEs had significantly higher LIP values than did the control group (1.94+/-0.46 microM vs. 1.62+/-0.49 microM, p=0.02). Except for the leukocyte number (WBCs), the groups did not differ in other inflammatory markers (CRPus, CD 163, MPO, MMP-1). Similarly, there were no differences in the markers of endothelial dysfunction (ICAM, VCAM, E-selectin, vWF). The CVE group had higher pulse pressures, levels of markers of impaired arterial elasticity (AI, Young´s modulus, pulsatility, stiffness index), IMT values and ABI values. The LIP concentration was significantly correlated with the transferrin receptor/ferritin ratio, hepcidin levels, VFT content and the ABI and ET values. Patients with a history of CVE have significantly higher concentrations of iron in their intracellular LIP in circulating monocytes than do healthy controls. The independent and significant correlation of LIP with markers of the progression of atherosclerosis and arterial stiffness suggests LIP as a possible novel marker of atherosclerotic activity.

Glucose and its metabolites have distinct effects on the calcium-induced mitochondrial permeability transition.

Mitochondrial production of reactive oxygen species (ROS) due to up-regulated glucose oxidation is thought to play a crucial, unifying role in the pathogenesis of chronic complications associated with diabetes mellitus. Mitochondrial permeability transition (MPT) is an interesting phenomenon involved in calcium signalling and cell death. We investigated the effects of glucose and several of its metabolites on calcium-induced MPT (measured as mitochondrial swelling) in isolated rat liver mitochondria. The presence of glucose, glucose 1-phosphate (both at 30 mM) or methylglyoxal (6 mM) significantly slowed calcium-induced mitochondrial swelling. Thirty mM glucose also resulted in a significant delay of MPT onset. In contrast, 30 mM fructose 6-phosphate accelerated swelling, whereas glucose 6-phosphate did not influence the MPT. The calcium binding potentials of the three hexose phosphates were tested and found similar. In vitro hydrogen peroxide production by mitochondria respiring on succinate in the presence of rotenone was independent of mitochondrial membrane potential and increased transiently during calcium-induced MPT. Inhibition of MPT with cyclosporine A resulted in decreased mitochondrial ROS production in response to calcium. In contrast, inhibition of MPT by methylglyoxal was accompanied by increased ROS production in response to calcium. In conclusion, we confirm that methylglyoxal is a potent inhibitor of MPT. In addition, high levels of glucose, glucose 1-phosphate and fructose 6-phosphate can also affect MPT. Methylglyoxal simultaneously inhibits MPT and increases mitochondrial ROS production in response to calcium. Our findings provide a novel context for the role of MPT in glucose sensing and the cellular toxicity caused by methylglyoxal.