[Regression analysis of red cell distribution width and mean platelet volume in patients with acute myocardial infarction].

OBJECTIVE: To investigate clinical implications of changes in red cell distribution width (RDW) and mean platelet volume (MPV) in patients with acute myocardial infarction. METHODS: A total of 127 patients (90 men and 37 women) were enrolled in this analysis, including 66 with acute myocardial infarction (AMI) and 61 with unstable angina (UA). The patients' baseline demographic and clinical data were compared between the two groups including age, hypertension, diabetes, smoking, BMI, blood biochemical profiles, cardiac functions and platelet and red blood cell parameters. The patients were further divided into subgroups according to the RDW 50% cumulative frequency, and the MPV, P-LCR, hsCRP, NT-proBNP, RBC, Dimer and MCV were compared. The correlations between platelet and erythrocyte test results were evaluated in both the AMI and UA patients. Regression analysis was performed to identify the factors affecting the RDW in the AMI group and a regression model was established. RESULTS: The platelet and red blood cell test results, P-LCR, MPV, and RDW differed significantly between AMI and UA groups (P<0.01 or 0.05). Correlation analysis showed a significant positive correlation between RDW and MPV in AMI group (r=0.34, P<0.01). Between the subgroups with different RDW 50% cumulative frequencies, MPV, P-LCR, hsCRP, D-Dimer, and NT-proBNP all differed significantly (P<0.05 or 0.01). In AMI group, with RDW as the dependent variable, we established a multivariate regression model of RDW=0.19MPV+10.83. CONCLUSION: RDW and MPV are closely correlated in patients with AMI. In multiple regression analysis, MPV can explain the changes in RDW in patients with AMI.

Role of Kir2.1 in human monocyte-derived foam cell maturation.

The role of K(+) channels in macrophage immunomodulation has been well-established. However, it remains unclear whether K(+) channels are involved in the lipid uptake of macrophages. The expression and function of the inward rectifier potassium channel (Kir2.1, KCNJ2) in Human acute monocytic leukemia cell line (THP-1) cells and human monocytes derived macrophages (HMDMs) were investigated using RT-PCR and western blotting, and patch clamp technique. The expression of scavenger receptors in THP-1-derived macrophages was detected using western blotting. Expressions of Kir2.1 mRNA and protein in HMDMs were significantly decreased by 60% (P < 0.05) and 90% (P < 0.001) on macrophage maturation, but overexpressed by approximately 1.3 (P > 0.05) and 3.8 times (P = 0.001) after foam cell formation respectively. Concurrently, the Kir2.1 peak current density in HMDMs, mature macrophages and foam cells, measured at -150 mV, were -22.61 ± 2.1 pA/pF, -7.88 ± 0.60 pA/pF and -13.39 ± 0.80 pA/pF respectively (P < 0.05). In association with an up-regulation of Kir2.1 in foam cells, the SR-A protein level was significantly increased by over 1.5 times compared with macrophages (P < 0.05). THP-1 cells contained much less lipids upon Kir2.1 knockdown and cholesterol ester/total cholesterol ratio was 29.46 ± 2.01% (P < 0.05), and the SR-BI protein level was increased by over 6.2 times, compared to that of macrophages (P < 0.001). Kir2.1 may participate in macrophage maturation and differentiation, and play a key role in lipid uptake and foam cell formation through modulating the expression of scavenger receptors.

3.0 T MRI arterial spin labeling and magnetic resonance spectroscopy technology in the application of Alzheimer's disease.

The purpose of this study was to investigate the changes in the cerebral blood flow (CBF) and spectrum variables in the posterior cingulate region of patients with AD under the detection of arterial spin labeling (ASL) and magnetic resonance spectroscopy (MRS). A total of 20 AD patients (8 males and 12 females; mean age, 64.84±8.82 years) and 20 healthy controls (9 males and 11 females; mean age, 64.94±7.93 years) were included in this study for analysis. All images were obtained using a 3.0-T MR imager and an 8-channel head array receiving coil. MRS measurements were conducted exploring variables of metabolite ratios. Statistical analyses were conducted with the SPSS 11.0 statistical software package. Findings in the present study revealed a significant difference in the mean MMSE scores between the AD group and the healthy control group (16.21±4.01 vs. 27.35±1.01, P<0.01). Compared with the healthy control group, CBF in the bilateral frontal region showed a significant decrease in the AD group (right frontal: 83.5±7.2 vs. 110±11.5, P<0.05; left frontal: 85.6±8.1 vs. 108.7±12.2, P<0.05, respectively), and a similar association was also observed in the TL, TPJ, parietal, and hippocampal regions (all P<0.05). MRS imaging in the posterior cingulate region showed a significant reduction in the NAA/Cr ratio in the AD group (1.43±0.1 vs. 1.49±0.0, P<0.05). Additionally, we found that the MI/Cr and Cho/Cr ratios were higher than normal controls in patients with AD (all P<0.05). Our results suggested that 3D ASL detection combined with MRS in studying AD could show the regional hypo-perfusion with the decrease of CBF and the abnormal metabolic changes of the posterior cingulate cortex.

[Inhibition of human macrophage-derived foam cell differentiation by blocking Kv1.3 and Kir2.1 channels].

OBJECTIVE: To investigate the expression of Kv1.3 and Kir2.1 during human monocyte-derived macrophages differentiation into foam cells and their function in foam cells formation. METHODS: The human macrophage-derived foam cells were obtained by incubating macrophages with ox-LDL (30 mg/L) for 60 h. The expression of Kv1.3 and Kir2.1 channels were examined by immunocytochemistry, RT-PCR and Western blot. Effects of channel blockers (rMargatoxin and BaCl2) on the cellular cholesterol metabolism were studied by measuring the cellular contents of total cholesterol (TC), free cholesterol (FC), and cholesterol ester (CE) in the presence or absence of the channel blockers. RESULTS: After incubating macrophages with 30 mg/L ox-LDL for 60 h, the cellular contents of TC, FC and CE were markedly increased and the ratio of CE/TC was raised from (14.4+/-6.8)% to (57.9+/-3.5)% (P<0.05), which indicated that the cells had differentiated into foam cells. The expression of Kv1.3 and Kir2.1 channels appeared no obvious difference when differentiating into foam cells (P>0.05); After being blocked specifically (rMargatoxin: 0.1, 10 nmol/L; BaC(12): 75, 125 micromol/L), the cellular contents of TC and CE were markedly reduced without exception and the ratios of CE/TC were all less than 50% (P<0.05). CONCLUSION: Both Kv1.3 and Kir2.1 channels play a critical role in differentiation of macrophages into foam cells and blockage of corresponding potassium channels would prevent the formation of the foam cells.

Inhibitory effects of blocking voltage-dependent potassium channel 1.3 on human monocyte-derived macrophage differentiation into foam cells.

OBJECTIVE: To investigate the expression of voltage-dependent potassium channel 1.3 (Kv1.3) mRNA and protein during human monocyte-derived macrophage differentiation into foam cells and its function in foam cell formation. METHODS: Human peripheral blood monocytes were isolated from healthy male volunteers by density gradient centrifugation and then by adherent method. The obtained monocytes were cultured for 5 days to differentiate into macrophages. Based on establishment of the human macrophage-derived foam cell model, the expression of Kv1.3 channel was investigated by immunocytochemical staining, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Furthermore, the effects of rMargatoxin, a Kv 1.3 channel-specific inhibitor, on cholesterol metabolism in macrophages incepting oxidized low density lipoprotein (OxLDL) were studied. RESULTS: After the macrophages co-incubated with 30 mg/L OxLDL at 37 degrees C for 60 hours, the cellular volume obviously enlarged and many red lipid granules were deposited in cytoplasm. The total amount of cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) in cells markedly increased and the ratio of CE/TC rose from (14.4+/-6.8)% to (57.9+/-3.5)% (n=7, P<0.05). However, the expression of Kv1.3 channel had no significant change. rMargatoxin (0.1 nmol/L and 10 nmol/L) markedly reduced the contents of TC, FC and CE in macrophages and the ratios of CE/TC decreased to (42.8+/-11.6)% and (22.6+/-8.0)%, respectively (n=7, P<0.05). Meanwhile, the red lipid granules deposited in the cytoplasm of macrophages also decreased. CONCLUSION: These data clearly show that the expression of Kv1.3 channel does not change obviously during human monocyte-derived macrophage differentiation into foam cells and the blocking of it would prevent foam cell formation.

[Inhibitory effect of blocking MaxiK channel on human monocyte-derived macrophages differentiation into foam cells].

AIM: To investigate the expression of high-conductance Ca2+-activated potassium channel (MaxiK channel) mRNA and protein during human monocyte-derived macrophage differentiation into foam cells and to study its function in foam cell formation. METHODS: Human peripheral blood monocytes were isolated from healthy male volunteers by density gradient centrifugation and then by adherent method. The obtained monocytes were cultured for 5 days to differentiate into macrophages. Based on establishment of human macrophage-derived foam cells model, the expression of MaxiK channel alpha-subunit was investigated by immunocytochemical staining, RT-PCR and Western blot. Furthermore, the effect of Paxilline, a MaxiK channel-specific inhibitor, on cholesterol metabolism in macrophages incepting oxidized low density lipoprotein (OxLDL) was studied. RESULTS: After the macrophages were co-incubated with 30 mg/L OxLDL at 37 degrees C for 60 hours, the cellular volume obviously enlarged and many red lipid granules were deposited in cytoplasm. The total amount of cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) in cells markedly increased and the ratio of CE/TC rose from (14.437+/-6.781)% to (57.946+/-3.507)% (n=7, P<0.05). However, the expression of MaxiK channel alpha-subunit had no significant change (P<0.05). Paxilline (5 micromol/L and 10 micromol/L) markedly reduced the content of TC, FC and CE in macrophages and the ratio of CE/TC decreased to (41.217+/-5.584)% (5 micromol/L Paxilline) and (18.017+/-11.559)% (10 micromol/L Paxilline), respectively (n=7, P<0.05). Meanwhile, the red lipid granules deposited in the cytoplasm of macrophages also decreased. CONCLUSION: Blocking MaxiK channel can inhibit human monocyte-derived macrophage to be differentiated into foam cells.

The expression of maxiK channel alpha--subunit during human macrophages differentiating into foam cells.

OBJECTIVE: To investigate the expression of MaxiK channel alpha-subunit during human monocyte-derived macrophages differentiating into foam cells. METHODS: Human peripheral blood monocytes were isolated from male healthy volunteers by density gradient centrifugation, which, by culture, differentiated further into macrophages as a homogeneous monocyte population. The foam cell model originated from human macrophage was established by incubating macrophages with oxidized low density lipoprotein (OxLDL). The expression of MaxiK channel alpha-subunit was investigated by RT-PCR techniques, Western blotting and immunocytochemistry. RESULTS: After incubating macrophages with 30 mg/L OxLDL for 60 hours, the cellular contents of total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) were markedly increased and the ratio of CE/TC was further raised from (14.437 +/- 6.781) % to (57.946 +/- 3.507) %. Although the expression of MaxiK channel alpha-subunit was downregulated during human monocyte-derived macrophages differentiating into foam cells, there was no significant difference between macrophages and foam cells (P > 0.05). CONCLUSION: That 30 mg/L OxLDL can lead the monocyte-derived macrophage cultured for 60 hours to differentiate into foam cell, but the expression of MaxiK channel alpha-subunit does not change obviously.

Expression of Kir2.1 channel during differentiation of human macrophages into foam cells.

OBJECTIVE: Detected in non-transformed bone marrow-derived macrophages (BMDM) and identified as one of the key channels in modulating macrophage proliferation, activation and apoptosis, Kir2.1 channel is also characterized to play a crucial role in cell differentiation. The purpose of this study was to investigate the expression of Kir2.1 channel mRNA and protein during human monocyte-derived macrophage differentiation into foam cells. METHODS: Human peripheral blood monocytes were isolated from healthy male volunteers by density gradient centrifugation and then by adherence method. The macrophages identified as a homogeneous population of adherent cells were obtained after 5 days of culture. Expression of Kir2.1 channel during human macrophage differentiation into foam cells was investigated by RT-PCR, Western blotting and immunocytochemistry, respectively. RESULTS: After incubation of the macrophages with 30 mg/L OxLDL at 37 degrees C for 60 h, the cells were obviously enlarged in size and numerous red lipid granules observed under optical microscope. The cellular contents of the total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) were markedly increased from 54.79+/-28.304 mg/g, 47.968+/-26.787 mg/g and 6.822+/-3.437 mg/g to 229.775+/-57.453 mg/g, 96.241+/-24.003 mg/g and 133.535+/-36.292 mg/g, respectively; the CE/TC ratio rose from (14.437+/-6.781)% to (57.946+/-3.507)% (n=7, P<0.05), suggesting the phenotype of foam cells. However, there was no significant difference in the relative expression of Kir2.1 channel mRNA between the macrophages and foam cells [(59.074+/-10.566)% vs (46.98+/-12.527)%, n=5, P>0.05], nor was there significant difference in the relative expression of Kir2.1 channel protein between them [(60.527+/-18.621)% vs (50.243+/-11.583)%, n=6, P>0.05]. CONCLUSION: Incubation of human monocyte-derived macrophages with 30 mg/L OxLDL for 60 h induces the differentiation of the cells into foam cells, but the expression of Kir2.1 channel does not change obviously.