1.Activation of extracellular-signal regulated kinase and protein phosphatases in human atria during atrial fibrillation
Hui YAN ; Junzhu CHEN ; Jianhua ZHU ; Shenjiang HU ; Qianmin TAO
Chinese Journal of Pathophysiology 2000;0(08):-
AIM: The purpose of this study was to determine whether the signal transduction systems were activated at the molecular atrial tissue level in patients with atrial fibrillation (AF) and whether atrial expression of extracellular-signal regulated kinase (ERK) and protein phosphatases is altered. METHODS: Atrial tissue sample of 30 patients undergoing cardiac surgery were examined. 20 patients had AF, 10 patients had no history of AF. The mRNA expression of calcineurin B and MKP-1 were detected by semi-quantitative RT-PCR. ERK1 and phospho-ERK1 were analyzed at the protein level by Western blot. RESULTS: Western blot analysis showed that atrial fibrillation did not induce significant change in ERK1 expression level in the left atrium. In contrast , phospho-ERK1 content was increased in the patients with AF in comparison with those who had sinus rhythm (SR). The mRNA expression of calcineurin B and MKP-1 in the patients with AF were significantly higher than that in patients with SR. CONCLUSION: The activation of extracellular-signal regulated kinase and protein phosphatases may have correlation with the initiation or maintenance of atrial fibrillation.
2.Effects of hydrogen peroxide on cell proliferation and expression of gelatinase A and its inhibitor in vascular smooth muscle cells
Xiaogang GUO ; Junzhu CHEN ; Jianhua ZHU ; Liangrong ZHENG ; Furong ZHANG ; Qianmin TAO ; Yun ZHANG
Chinese Journal of Pathophysiology 2000;0(12):-
AIM: To study the effects of hydrogen peroxied (H 2O 2) on cell proliferation and transcription of gelatinase A (MMP-2) and its inhibitor (TIMP-2) in vascular smooth muscle cells (VSMC). METHODS: Cell proliferation and toxicity by H 2O 2 were tested through MTT. The expression of MMP-2 mRNA and TIMP-2 mRNA in VSMC were evaluated by RT-PCR. RESULTS: The present study showed that H 2O 2 (more than 300 ?mol/L)was lethal to VSMC. 0 01-50 ?mol/L H 2O 2 promoted proliferation of VSMC in a time-dependant manner. A value (optical density) was reached to peak at 24 h after continuing stimulation of 10 ?mol/L H 2O 2. MMP-2/?-actin mRNA ratio significantly increased after stimulation with 1 ?mol/L?10 ?mol/L H 2O 2. TIMP-2/?-actin mRNA ratio was not significantly fluctuated at 12 h?24 h?36 h?48 h after continuing stimulation with 1 ?mol/L, 10 ?mol/L, and 50 ?mol/L H 2O 2.CONCLUSION: H 2O 2 at suitable concentrations stimulated proliferation of VSMC and induced transcription of MMP-2 gene in VSMC. There was no effect of H 2O 2 on transcription of TIMP-2 gene in VSMC. These results imply that H 2O 2 takes part in the pathological course of vascular remodeling through VSMC.
3.Effects of diltiazem on platelet activation and cytosolic calcium during percutaneous transluminal coronary angioplasty
Hemin DAI ; Junzhu CHEN ; Qianmin TAO ; Jianhua ZHU ; Furong ZHANG ; Liangrong ZHENG ; Yuangang QIU
Chinese Journal of Pathophysiology 2000;0(07):-
AIM: To evaluate effects of diltiazem on platelet hyperreactivity in situations associated with endothelial injury and their possible relationship to cytosolic calcium concentration. METHODS: Blood samples were collected at 7 time points from 35 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) who received combined diltiazem and aspirin/ticlopidine therapy or aspirin/ticlopidine therapy alone. Platelet expression of glycoprotein Ⅱb/Ⅲa and cytosolic calcium concentration were measured, respectively, by whole blood flow cytometry and fluorospectrophotometry. The effects of diltiazem of different concentrations on expression of glycoprotein Ⅱb/Ⅲa were also studied in vitro in blood samples from patients with chronic stable angina. RESULTS: Of the two treatments, aspirin/ticlopidine therapy did not prevent an acute increase of expression of glycoprotein Ⅱb/Ⅲa 5 minutes and 10 minutes after first inflation and 10 minutes after PTCA, whereas combined diltiazem and aspirin/ticlopidine therapy had a significant inhibitory effect. In the group receiving aspirin/ticlopidine therapy, there was a short-term elevation of platelet [Ca~(2+)]i immediately following PTCA which was significantly reduced by diltiazem treatment. Expression of glycoprotein Ⅱb/Ⅲa was significantly inhibited in vitro by diltiazem in the concentration of 200 ?g/L or higher, but not 50 ?g/L. CONCLUSIONS: Combined diltiazem and aspirin/ticlopidine therapy significantly inhibited platelet activation that continued in the presence of conventional aspirin/ticlopidine treatment. Antiplatelet effects of diltiazem were probably a consequence of reduction of platelet [Ca~(2+)]i and may only be achieved in higher than therapeutic concentrations. [
5.Effects of homocysteine on number and activity of endothelial progenitor cells from peripheral blood
Xingxiang WANG ; Yunpeng SHANG ; Junhui ZHU ; Junzhu CHEN ; Jianhua ZHU ; Qianmin TAO ; Xiaogang GUO ; Zhankun WANG ; Li ZHANG
Chinese Journal of Pathophysiology 2000;0(07):-
AIM: To investigate whether homocysteine (Hcy) has influences on endothelial progenitor cell (EPCs) number and activity from peripheral blood. METHODS: Total mononuclear cells (MNCs) were plated on fibronectin-coated culture dishes and cultured for 7 days, and then attached cells were stimulated with Hcy or vehicle control for 6 h, 12 h, 24 h and 48 h. The adhesion, proliferation, migration and in vitro vasculogenesis activity of EPCs were assayed, respectively. RESULTS: Incubation of isolated human MNCs with Hcy dose and time-dependently decreased the number of EPCs with maximum at 200 (?mol/L) for 24 hours (35.7?6.7 vs 62.5?10.6, P