Granulocyte colony-stimulating factor reduces cardiomyocyte apoptosis and improves cardiac function in adriamycin-induced cardiomyopathy in rats.

BACKGROUND: Cardiomyocyte apoptosis reportedly participates in the occurrence and progression of dilated cardiomyopathy (DCM). Recent studies have shown that granulocyte colony-stimulating factor (G-CSF) enhances bone marrow cells migration to the damaged heart in the DCM model and improves the ultrastructure of the cardiomyocyte in adriamycin (ADR) induced DCM. However, its influence on cardiac pump function and cardiomyocyte apoptosis has not been studied. METHODS AND MATERIALS: Wistar Rats were randomly grouped into control, ADR, ADR+PBS, ADR+G-CSF group (n = 10). ADR (2.5 mg/kg, 6 times for 2 weeks) was administered intraperitoneally in all rats except the control group. After 2 weeks, the rats in ADR+G-CSF group were injected with G-CSF (50 microg/kg/day for 8 days) subcutaneously. Cardiac function was evaluated by echocardiogram and cardiac catheterization after 4 weeks. Cardiomyocytes apoptosis and apoptosis-related protein Fas were detected by in situ terminal deoxynucleotidyl transferase assay (TUNEL method) and Western blot, respectively. RESULTS: The ADR and ADR+PBS groups showed significant deteriorations of left ventricular functions and high cardiomyocyte apoptosis index, as well as high Fas expressions. Meanwhile, the ADR+G-CSF group showed significant improvement in LV function, inhibition of cardiomyocyte apoptosis compared with the ADR and ADR+Phosphate-Buffered Saline PBS group. The Fas protein expression was remarkably attenuated as well. CONCLUSION: Our results suggest that administration of G-CSF inhibited cardiomyocyte apoptosis and Fas protein expression and contributes to improving cardiac pump function in vivo in ADR induced DCM rat model.

Association of 4G/5G polymorphism in PAI1 promoter with PAI1 level in deep vein thrombosis.

OBJECTIVE: To reveal the association of 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor 1 gene (PAI1) with plasma PAI1 level in deep vein thrombosis (DVT) in Chinese Han ethnic group. METHODS: One hundred and twenty Chinese DVT patients and 120 healthy controls were recruited. The PAI1 promoter 4G/5G polymorphism was detected using polymerase chain reaction (PCR). The antigen of tissue-type plasminogen activator (tPA) or PAI1 was quantified by a commercially available enzyme-linked immunosorbent assay (ELISA) in DVT cases and health controlsì respectively. RESULTS: Neither in the distribution of PAI1 promoter 4G/5G polymorphism nor in the frequencies of 4G and 5G allele was there a difference between two groups. The levels of PAI1 antigen in the carriers of the 4G/4G genotype were significantly higher than those either in the 4G/5G genotype or in the 5G/5G genotype; In the 4G/5G genotype or in the 5G/5G genotype the TG levels are an independently determinant factor of PAI1 antigen levels. CONCLUSION: There is a close relationship of the PAI1 4G/5G polymorphism to its plasma level in deep vein thrombosis in Chinese Han ethnic group, although lack of association between this genetic variation and risk of DVT suggest no major cause-effect pathogenic role of this polymorphism by itself.

[Intravascular ultrasound study of coronary remodeling and determination of matrix metalloproteinase and hypersensitive C-reactive protein].

OBJECTIVE: To investigate remodeling characteristics of coronary lesions in patients with acute coronary syndromes (ACS) versus stable angina pectoris (SA) using intravascular ultrasound (IVUS), and to explore the relationship between arterial remodeling and clinical presentation or matrix metalloproteinase (MMPs) or hyper-sensitive C-reactive protein (hs-CRP). METHODS: We studied culprit lesions of 38 patients with ACS and 18 patients with SA using IVUS before coronary intervention. The lesion site and a proximal or distal reference site including the external elastic membrane (EEM) area and lumen area were analyzed. Plaque area and remodeling index (RI) were calculated, and directions of arterial remodeling were determined. Positive remodeling was defined as RI > 1.05 and negative remodeling as RI < 0.95. We analyzed the culprit lesion qualitatively, identified high risk plaque and compared them in each group. The blood level of MMP-2, MMP-9 and hs-CRP in each group were also determined. RESULTS: The plaque area at culprit lesions in patients with ACS was significantly larger (11.94 +/- 4.90 versus 9.17 +/- 3.36 mm2; P = 0.035), and also the RI in ACS group was significantly greater than that of patients with SA (0.972 +/- 0.222 versus 0.796 +/- 0.130; P = 0.003). The distribution of remodeling in these two groups was different: positive remodeling was more frequent in ACS group than in SA group (34.2% versus 5.6%, P = 0.047), whereas negative remodeling was more frequent in SA group (52.6% versus 88.9%, P = 0.003). There was higher incidence of high risk plaque in ACS group compared to SA (76.3% versus 50.0%, P = 0.040). The level of serum MMP-2 in ACS group was higher than that of SA group (250.65 +/- 47.97 microg/L versus 214.21 +/- 47.20 microg/L, P = 0.029). The same applied for plasma MMP-9 (84.26 +/- 9.78 microg/L versus 68.46 +/- 22.82 microg/L, P = 0.038) and serum hs-CRP (3.62 +/- 3.37 mg/L versus 1.48 +/- 1.52 mg/L, P = 0.041). CONCLUSIONS: Positive remodeling, larger plaque area and higher incidence of high risk plaque are associated with ACS, whereas negative remodeling is more common in patients with SA. This association between the extent of remodeling and clinical presentation may reflect a greater tendency that plaques with positive remodeling can cause ACS. The change of level of MMP-2, MMP-9 and hs-CRP in ACS patients may be helpful in investigating vulnerable plaques.

[Changes of angiotensin II and its receptor during the development of chronic intermittent hypoxia-induced hypertension in rats].

OBJECTIVE: To observe the changes of angiotensin II (ATII) and ATII type-1 receptor (AT1R) during the development of chronic intermittent hypoxia (CIHO)-induced hypertension in rats, and the effect in the mechanism of CIHO-induced hypertension. METHODS: Seventy-two male Wistar rats were divided into three groups:intermittent hypoxia group (IH), sham control group (SC) and control group (UC). By using supply of nitrogen (30 s each cycle) followed by compressed air (30 s each cycle) into the exposure chambers (4% - 6% nadir ambient oxygen with return to 21%), IH rats were subjected to intermittent hypoxia every 60 s for 8 h/d during the diurnal sleep period. SC rats were similarly treated but received compressed air instead of nitrogen. UC rats were not treated. Mean arterial pressure (MAP), the levels of ATII and renin activity (RA) in plasma as well as the expression of AT1R mRNA in tissue were measured on day 7, 21 and 42 after experiment. RESULTS: MAP was significantly elevated in IH rats [(102.2 +/- 6.2) mm Hg, 1 mm Hg = 0.133 kPa] compared with initial MAP [(94.1 +/- 4.3) mm Hg, P < 0.01] and compared with that in SC [(95.7 +/- 3.6) mm Hg], UC [(97.2 +/- 3.6) mm Hg, all P < 0.05] on day 42. The levels of ATII and RA in plasma in IH rats increased gradually over time, and RA started to increase significantly on day 7 [(3.86 +/- 1.25) ng.ml(-1).h(-1)] compared with that in SC [(2.73 +/- 0.98) ng.ml(-1).h(-1)], UC [(2.55 +/- 0.87) ng.ml(-1).h(-1), all P < 0.05], and ATII started to increase significantly on day 21 [(214 +/- 41) ng/L] compared with that in SC [(124 +/- 21) ng/L], UC [(121 +/- 18) ng/L, all P < 0.01]. The RA and ATII levels in plasma showed positive correlation with MAP (r = 0.529, P = 0.008; r = 0.475, P = 0.019 respectively). The expression of AT1R mRNA in heart, kidney and aorta in IH rats showed no differences compared with that in SC and UC group (all P > 0.05). All indices were not different between SC and UC rats at any time point (all P > 0.05). CONCLUSION: CIHO can cause the levels of circulating RA and ATII to increase, but has no effects on AT1R mRNA expression in tissue, which suggests that activated renin-angiotensin system may contribute to the pathogenesis of CIHO-induced hypertension.

[Level of tissue plasminogen activator protein in pulmonary artery in acute pulmonary thromboembolism in rabbit].

OBJECTIVE: To study the changes in tissue plasminogen activator(t-PA) protein in pulmonary artery and its clinical significance after acute pulmonary thromboembolism (PTE). METHODS: Thirty rabbits were randomly divided into four groups after replicating a model of acute PTE in rabbit by thrombi occlusion method. Specimens were obtained from both normal and morbid pulmonary artery 3, 8 and 24 hours after APE, and protein contents of t-PA were determined using immunohistochemical method. RESULTS: A few endothelial cells and smooth muscle cells of the normal pulmonary artery were positive for t-PA. After 3 hours of PTE, there was no significant changes in t-PA positive stain among embolismic, non-embolismic and normal pulmonary artery. After 8 and 24 hours of PTE, strong positive staining was found in the residual endothelial cells and a part of smooth muscle cells (all P<0.01). CONCLUSION: There is significantly strong positive staining for t-PA in the pulmonary artery wall after pulmonary embolism, implying that the local fibrinolysis activity was enhanced, and it might be helpful for lysis of the embolus.