Lipidomics reveals accumulation of the oxidized cholesterol in erythrocytes of heart failure patients.

Lipids play an important role in the pathogenesis of cardiovascular disease. Changes in lipids of erythrocytes are indicative of the outcome of pathophysiological processes. In the present study, we assessed whether the lipid profiles of erythrocytes from heart failure (HF) patients are informative of their disease risk. The lipidomes of erythrocytes from 10 control subjects and 29 patients at different HF stages were analyzed using liquid chromatography time-of-flight mass spectrometry. The lipid composition of erythrocytes obtained from HF patients was significantly different from that of normal controls. The levels of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and sphingomyelins decreased in HF erythrocytes as compared with those of control subjects; however, the levels of lysoPCs, lysoPEs, and ceramides increased in HF erythrocytes. Notably, the oxidized cholesterol 7-ketocholesterol (7KCh) accumulated to higher level in HF erythrocytes than in plasma from the same patients. We further validated our findings with a cohort of 115 subjects of control subjects (n=28) and patients (n=87). Mechanistically, 7KCh promoted reactive oxygen species (ROS) formation in cardiomyocytes; and induced their death, probably through an ATF4-dependent pathway. Our findings suggest that erythrocytic 7KCh can be a risk factor for HF, and is probably implicated in its pathophysiology.

Ocular responses and visual performance after emergent acceleration stress.

PURPOSE: To evaluate visual function after emergent acceleration stress. METHODS: Sixteen subjects were enrolled in this study. Human ejection seat trainer was used to induce six times gravitational force in the head-to-toe (z-axis) direction (+6 Gz). Visual performance was evaluated using the visual chart and contrast sensitivity (CS) at indicated times. Ocular reactions were assessed with biomicroscopy and topographic mapping. RESULTS: Temporary visual acuity reduction (0.02 ± 0.05 vs. 0.18 ± 0.08 logMAR visual acuity [VA]; P < 0.05) and ocular reactions were observed after ejection. These reactions included changes in increasing anterior chamber depth (ACD; 3.18 ± 0.29 vs. 4.48 ± 0.32 mm; P < 0.05) and pupillary dilation (PD; 3.56 ± 0.72 vs. 5.64 ± 0.56 mm; P < 0.05). The ACD deepening continued at 15 minutes (4.37 ± 0.26 mm; P < 0.05), and PD persisted at 30 minutes after the gravitational stress (5.42 ± 0.54 mm, P < 0.05). CS decreased significantly at all spatial frequencies immediately after ejection. However, CS returned to the initial range at high spatial frequency by 30 minutes. CONCLUSIONS: Emergent acceleration force induces significant ocular responses and visual fluctuation. Prolonged ACD deepening (>15 minutes) and PD (>30 minutes) were noted, but cornea and refraction remain stable. CS at all spatial frequencies revealed remarkable reduction immediately after ejection, and recovered to baseline levels within 30 minutes only at high spatial frequency. Neuroretinal function may involve visual fluctuation after acceleration stress, because visual fluctuation corresponds with the characters of neuroretinal function. However, further studies are necessary.