[Effect of Ginkgo biloba Tablet on the Expression of Scavenger Receptor A of the Aortic Wall in Atherosclerotic Rats].

OBJECTIVE: To observe the expression of Ginkgo biloba Tablet (GbT) on scavenger receptor A (SRA) of the aortic wall and changes of serum inflammatory factors in atherosclerotic rats, and to explore its new mechanism for fighting against atherosclerosis (AS). METHODS: Totally 45 male Wistar rats were randomly divided into the control group, the model group, the GbT group, 15 rats in each group. Levels of blood glucose, blood lipids, blood calcium, serum C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (slCAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in all rats. The expression of SRA in the aortic wall of atherosclerotic rats was observed by immunohistochemical assay. The correlation between the expression of SRA and levels of in-flammatory factors was also observed. RESULTS: Compared with the control group, blood glucose and blood calcium obviously increased (P < 0.05); levels of TG, TC, and LDL-C were significantly elevated (P < 0.01); neointimal areas were significantly thickened, increased intima percentage was significantly enlarged, narrowed lumen index was significantly reduced; levels of CRP, sICAM-1, and sVCAM-1 were significantly elevated in the model group (all P < 0.01). Compared with the model group, blood glucose and blood calcium obviously decreased (P < 0.05); levels of TG, TC, and LDL-C significantly decreased (P < 0.01) in the GbT group. Aortic lumens were obviously narrower in the model group than in the GbT group (P < 0.05). SRA expressed at the aortic wall. The aforesaid 3 indices were significantly improved in the GbT group than in the model group (P < 0.01). Serum levels of CRP, sICAM-1, and sVCAM-1 were significantly decreased in the GbT group than in the model group (P < 0.01). Serum levels of CRP, sICAM-1, and sVCAM-1 were positively correlated with the percentage of SRA positive expression area (r = 0.701, 0.604, 0.581, all P < 0.01). CONCLUSIONS: Serum levels of inflammatory factors in atherosclerotic rats were elevated, and the expression of SRA in the aortic wall was enhanced. The expression of SRA was closely correlated with serum levels of inflammatory factors. GbT could decrease serum levels of inflammatory factors and inhibit the expression of SRA.

Reduction of Leukocyte Counts by Hydroxyurea Improves Cardiac Function in Rats with Acute Myocardial Infarction.

BACKGROUND This study aimed to decrease leukocytes counts by hydroxyurea (Hu) in an acute myocardial infarction (AMI) rat model and examine its effect on the inflammatory response of myocardial infarction and cardiac functions. MATERIAL AND METHODS AMI was successfully caused in 36 rats, and 12 control rats received sham operation. Rats in the AMI group were then randomly divided into Hu and vehicle group with 18 rats each. Rats in the Hu AMI group received Hu (200 mg/kg) intragastrically while vehicle AMI group received saline. Leukocytes counts, cardiac functions, myocardial tissue morphology, and levels of soluble intercellular adhesion molecule-1 (sICAM), P-selectin and platelet activating factor (PAF) were measured and compared among the three groups four weeks after AMI induction. RESULTS Leukocytes, neutrophils, and leukomonocyte counts in vehicle AMI rats were significantly higher than that of the normal control group (p<0.05). However, Hu treatment decreased their counts significantly (p<0.05). sICAM, P-selectin, and PAF level in vehicle AMI group were significantly higher than those of the normal group, and their level was also decreased by Hu treatment (p<0.05). Echocardiography analysis showed that Hu treatment increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) compared to that of vehicle AMI group (p<0.05). Histopathological examination showed that Hu significantly reduced the swelling of the heart muscle fiber in necrotic foci and the number of inflammatory cells infiltrated into myocardial interstitium compared to vehicle AMI group. CONCLUSIONS Decrease leukocytes counts by Hu significantly reduced inflammatory reaction and improved cardiac functions in AMI rats.

[Arterial remodeling at the reference site after angioplasty and the effect of granulocyte-macrophage colony-stimulating factor on remodeling].

OBJECTIVE: To observe the correlation of the arterial remodeling at the reference site and the lesion site and the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on arterial remodeling. METHODS: 28 healthy New Zealand White rabbits were randomized to 2 equal groups: GM-CSF group receiving subcutaneous injection of GM-CSF (10 microg x kg(-1)xd(-1)) for 7 days, and pure damage group given subcutaneous injection of equivalent normal saline foe 7 days. Seven days later the iliac arteries of all animals were damaged by balloon. The levels of nitrogen monoxide (NO) were detected before and 4 weeks after angioplasty. Histological sections of iliac from rabbits killed 4 weeks after angioplasty were analyzed. Lumen area (LA), external elastic lamina area (EELA), and intimal plus medial areas (I + M) were measured at the lesion(L) and reference(R) sites. RESULTS: The NO levels 4 weeks later of the GM-CSF group was 98 +/- 10 micromol/L, significantly higher than that of the pure damage group (83 +/- 12 micromol/L, P < 0.05). Morphometric analysis showed that the LA(L) of the pure damage group was (0.87 +/- 0.40) mm2, significantly smaller than that of the GM-CSF group [(1.34 +/- 0.52) mm2, P < 0.05]. The I + M(L) of the pure damage group was (2.62 +/- 0.48) mm2, significantly greater than that of the GM-CSF group [(2.26 +/- 0.43) mm2, P < 0.05]. There was no statistical significance in the EEL(L) between the 2 groups [(3.48 +/- 0.80) mm2 versus (3.60 +/- 0.91) mm2, P > 0.05]. Morphometric analysis showed that the LA(R) of the pure damage group was (1.60 +/- 0.48) mm2, significantly smaller than that of the GM-CSF group [(1.99 +/- 0.54) mm2, P < 0.05], whereas there was no statistical significance in the I + M(R) between the 2 groups. In both groups, LA(R) was significantly correlated with LA(L) (r = 0.919, P < 0.001); and EELA(R) was significantly correlated with EELA(L) (r = 0.909, P < 0.001) and I + M(R) (r = 0.685; P < 0.001). CONCLUSION: Remodeling affects both the lesion and the reference sites and appears to occur in parallel and proportionately at both sites. GM-CSF treatment increases re-endothelialization of the injured artery and inhibits unfavorable remodeling.

Rutin inhibits coronary heart disease through ERK1/2 and Akt signaling in a porcine model.

Rutin has a variety of pharmacological actions, including radical reactivity, and protective activity against lipid peroxidation, viruses and acute pancreatitis; thus, it may be used as a treatment for many diseases. The present study aimed to investigate whether rutin inhibits coronary heart disease through extracellular signal-regulated kinase (ERK) 1/2 and Akt signaling in a porcine model. Male Chinese miniature pigs were randomly divided into four groups: A sham group, a coronary heart disease (CHD) model group, a group receiving 15 mg/kg rutin for 8 weeks following CHD modeling and a group receiving 45 mg/kg rutin for 8 weeks following CHD modeling. The results suggested that treatment with rutin suppressed the reduction in left ventricular ejection fraction and increase in systolic internal diameter that occurred in CHD model pigs. Rutin administration reduced the infarct size of the myocardium, attenuated LVEF, increased LVID and inhibited urine protein concentration, BUN and Scr expression levels in CHD model pigs. Results from western blot analysis demonstrated that in CHD pigs treated with 45 mg/kg rutin, the CHD-associated increases in transforming growth factor ß1 and SMAD2 expression and reductions in phosphorylated (p)-ERK1/2 and p-Akt expression were attenuated. The present study suggests that rutin inhibits coronary heart disease through ERK1/2 and Akt signaling pathways in a porcine model.

[Atorvastatin inhibits scavenger receptor A and monocyte chemoattractant protein-1 expressions in foam cell].

OBJECTIVE: To investigate the effects of atorvastatin on expressions of scavenger receptor A and secretion of monocyte chemoattractant protein-1 (MCP-1) in foam cells. METHODS: THP-1 cells were induced to differentiate into macrophages by PMA and treated with 0.1% BSA (control), ox-LDL (100 mg/L) or ox-LDL plus atorvastatin (5, 10, 20 micromol/L) for 24 hours. MCP-1 concentration in cell substratum was measured by ELISA. Scavenger receptor A expression was observed under fluorescent microscope after incubated with DiI-Ac-LDL. The relationship between concentration of MCP-1 and the activity of scavenger receptor A was also analyzed. RESULTS: Compared to the control cells, MCP-1 concentration in ox-LDL treated cells was significantly increased after 6 hours, peaked at 12 hours and was still significantly increased after 24 hours (all P < 0.05 vs. baseline). The activity of scavenger receptor A was also significantly increased in ox-LDL treated cells (P < 0.01 vs. control). The activity of scavenger receptor A proteins correlated positively to the concentration of MCP-1 in ox-LDL treated cells (r = 0.683, P < 0.01). Atorvastatin significantly attenuated these changes in a dose-dependent manner. CONCLUSIONS: Scavenger receptor A and MCP-1 expressions were significantly increased in the course of monocyte lines THP-1 differentiating into macrophages and foam cells. The anti-atherosclerosis effect of atorvastatin might be partly achieved by inhibiting the secretion of MCP-1 and expression of scavenger receptor A in foam cells.

[Change of peripheral blood monocytes derived macrophage scavenger receptors activity in patients with coronary heart disease, and the intervention effect of ginkgo biloba extract].

OBJECTIVE: To observe the activity of peripheral blood monocytes (PBMs) derived macrophage scavenger receptors (MSR) and changes of serum inflammatory factor in peripheral blood in patients with coronary heart disease (CHD), and to evaluate the effect of Ginkgo biloba extract (GBE) on the MSR activity, to explore the relationship between inflammatory factor and scavenger receptors activity as well as the possible mechanism of GBE in stabilizing the atheromatous plaque. METHODS: Ninety-seven CHD patients with normal blood lipids were classified into the stable angina group, the unstable angina group and the acute myocardial infarction group, and 29 healthy persons were taken as control. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in all subjects were determined. And their PBMs were isolated, cultured in vitro, and transferred into macrophage to observe the effect of GBE on the expression of scavenger receptors. RESULTS: The levels of MSR activity, CRP, sICAM-1 and sVCAM-1 in patients with acute myocardial infarction > unstable angina > stable angina > control. CONCLUSION: GBE could down-regulate the MSR activity in CHD patients, which was positively correlated with levels of CRP, sICAM-1 and sVCAM-1. MSR activity could be taken as a monitoring criteria for active degree of vulnerable atherosclerosis plaque. GBE has the effect of suppressing MSR activity.

Enzymatic characterization of a type II isocitrate dehydrogenase from pathogenic Leptospira interrogans serovar Lai strain 56601.

Leptospira interrogans, a Gram-negative pathogen, could cause infections in a wide variety of mammalian hosts, but due to their fastidious cultivation requirements and the lack of genetic systems, the pathogenic factor is still not clear. Isocitrate dehydrogenase (IDH) is a key enzyme in the tricarboxylation (TCA) cycle, which could have an important impact on the growth and pathogenesis of the bacteria. In the present study, we first report the cloning, heterologous expression, and detailed characterization of the IDH gene from L. interrogans serovar Lai strain 56601(LiIDH). The molecular weight of LiIDH was determined to be 87 kDa by filtration chromatography, suggesting LiIDH is a typical homodimer. The optimum activity of LiIDH was found at 60 °C, and its optimum pH was 7.0 (Mn(2+)) and 8.0 (Mg(2+)). Heat inactivation studies showed that heat treatment for 20 min at 50 °C caused a 50 % loss of enzyme activity. LiIDH was completely divalent cation dependent as other typical dimeric IDHs and Mg(2+) was its best activator. The recombinant LiIDH specificities (kcat/Km values for NADP(+) and NAD(+)) in the presence of Mg(2+) and Mn(2+) were 6,269-fold and 1,000-fold greater for NADP(+) than NAD(+), respectively. This current work is expected to shed light on the functions of metabolic enzymes in L. interrogans and provide useful information for LiIDH to be considered as a possible candidate for serological diagnostics and detection of L. interrogans infection.