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Biomedical subjects

Shui-ping Zhao

Publications and source records attributed to Shui-ping Zhao.

At least 19 recordsLinked to original sources
PubMed2007

Effect of probucol on HDL metabolism and class B type I scavenger receptor (SR-BI) expression in the liver of hypercholesterolemic rabbits.

BACKGROUND: Scavenger receptor class B type I (SR-BI) is a major receptor for high-density lipoproteins (HDL) in the liver. Overexpression of SR-BI attenuated experimental atherosclerosis in murine models, concomitant with a reduction in plasma HDL-cholesterol levels. Probucol is known to be a potent hypolipidemic drug to regress xanthoma formation and carotid atherosclerosis in conjunction with a marked reduction in HDL-cholesterol levels. However, the mechanism by which probucol affects atherosclerosis is not completely understood, and the effect of probucol on the expression of SR-BI was controversial. The aim of this study was to know the effect of probucol on HDL metabolism and SR-BI expression in the liver. METHODS: Sixteen rabbits fed with high cholesterol diet for 8 weeks were randomly divided into two groups: (1) high cholesterol group (n = 8): maintained high cholesterol diet for 6 weeks; (2) probucol group (n = 8): the same cholesterol diet plus 1% probucol for 6 weeks. Control group (n = 8) was fed with normal diet for 14 weeks. The classical in situ two steps perfusion of the liver with collagenase IV was used to isolate the parenchymal hepatocytes. The selective uptake of HDL by hepatocytes was performed using the double radiolabelled HDL. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were used to evaluate SR-BI expression in the liver. RESULTS: Compared with control group, rabbits fed with high cholesterol diet showed higher levels of serum total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and HDL-C, all of which were significantly reduced by probucol treatment. The selective uptake of HDL CEs in probucol group (249.68 +/- 60.13 ng/mg cell protein) was about two folds higher as compared with the control group (122.47 +/- 54.06 ng/mg cell protein, P < 0.01) and high cholesterol group (104.92 +/- 47.91 ng/mg cell protein, P < 0.01), but it could not be reproduced in vitro. The expression of SR-BI were significantly decreased in the high cholesterol group (0.48 +/- 0.06) as compared with control group (0.65 +/- 0.06, P < 0.01). Probucol increased SR-BI expression (0.68 +/- 0.06, P < 0.01) as compared with high cholesterol group. The expression of SR-BI was positively associated with the selective CEs uptake (r = 0.47, P = 0.032). CONCLUSIONS: Probucol up-regulates SR-BI expression and enhance the uptake of HDL CEs by hepatocytes, which may help us to understand the anti-atherogenic properties and the HDL-C-lowering effect of probucol.

Animals↗
PubMed2007

Apolipoprotein M likely extends its anti-atherogenesis via anti-inflammation.

Apolipoprotein M (apoM), a novel human apolipoprotein recently discovered, predominantly presents in high density lipoprotein (HDL) in plasma, exclusively expressed in liver and in kidney. The present data demonstrated apoM protects against atherosclerosis (AS) primarily via partaking in prebeta-HDL formation and promoting cholesterol efflux to HDL. However, this lipid-metabolism-associated pathway seems unlikely responsible for all atheroprotective effects of apoM. Notably, the human apoM gene is just located in the major histocompatibility complex class III region (MHC-III) on chromosome 6, many genes in this region are related to the immune and inflammatory response. Furthermore, apoM has been documented to link with some inflammatory factors including platelet activating factor (PAF) and leptin. These evidences indicate that apoM may be involved in inflammatory activities in vivo and the potential immuno- and inflam-reactive property of apoM may contribute to the anti-inflammatory function of HDL, as generally acknowledged as an important atheroprotective mechanism of HDL.

Apolipoproteins↗
PubMed2006

[Efficacy and safety of extended-release niacin alone or with atorvastatin for lipid profile modification].

OBJECTIVE: To evaluate the efficacy and safety of extended-release niacin (niacin ER) either alone or in combination with atorvastatin for the lipid profile modification in the patients with coronary heart disease (CHD) and its equivalents. METHODS: One hundred and ten patients with CHD and its equivalents with serum total cholesterol (TC) > or = 3.5 mmol/L were randomly assigned into three treatment groups: (1) atorvastatin group (n = 38), receiving atorvastatin 10 mg/d for 8 weeks; (2) niacin ER group (n = 38), given niacin ER 500 mg/d for 4 weeks and then 1000 mg/d for 4 weeks; (3) combination treatment group (n = 34), treated with atorvastatin (10 mg/d) plus niacin ER, with the dose initiating from 500 mg/d, and increasing to 1000 mg/d after 4 weeks, for 8 weeks. The serums lipid profiles and adverse effects were assessed in all the patients before treatment, and 4 and 8 weeks after treatment. RESULTS: (1) After 8 weeks of treatment, the serum level of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were reduced by 30% and 16% respectively in the niacin ER group compared with the baseline values (both P < 0.05). After 8 weeks, the TC, low-density lipoprotein cholesterol (LDL-C), and TG in the atorvastatin group decreased by 19%, 26%, and 17% respectively compared with the baseline values (all P < 0.05). Combination treatment decreased the TC, LDL-C, and TG levels by 28%, 38%, and 39% respectively, and increased the HDL-C level by 23% (all P < 0.05). The improvement in TC and LDL-C achieved by combination treatment was superior to treatment of atorvastatin alone and treatment of niacin ER alone (all P < 0.05). (2) The rate of achieving the LDL-C goal of The National Cholesterol Education Program (NCEP) in Adult Treatment Panel III (ATP III) in the combination therapy group was 73.5%, significantly higher than those of the atorvastatin and niacin groups (47.7% and 42.1% respectively, both P < 0.05). (3) Adverse effect, such as flushing (15.8%) and gastrointestinal symptoms (23.7%) were found in the niacin ER group, however, no more adverse effects were found in the combination therapy group. There were no serious adverse events in all groups. CONCLUSION: Niacin ER has a favorable effect in modulating the blood lipid profile, especially in reducing TG and elevating HDL-C. Combined statin with niacin may produce a more global and effective improvement in lipid blood levels than monotherapy and is generally safe and well tolerable.

Aged↗
PubMed2006

Adipocyte: a potential target for the treatment of atherosclerosis.

Obesity is an independent risk factor for coronary heart disease, whereas the underlying mechanisms have not been fully elucidated. Adipocytes may produce various adipokines with favorable and unfavorable cardiovascular effects. The dysregulated secretion of adipokines by adipocytes may contribute to obese associated atherosclerosis. Adipocytes can also function as phagocytes to uptake and degrade oxidized low-density lipoprotein (Ox-LDL), suggesting that adipocytes possibly involve in clearance of Ox-LDL in blood. The dysfunctional adipocytes might be implicated in the atherogenesis. Some cardioprotective drugs mediate their cardiovascular benefits partly through their direct beneficial effects on adipocytes. Therefore, we hypothesized that adipocytes might be potential target for the treatment of atherosclerosis.

Adipocytes↗
PubMed2006

Probucol up-regulates paraoxonase 1 expression in hepatocytes of hypercholesterolemic rabbits.

Paraoxonase 1 (PON1), an HDL-associated enzyme, has anti-oxidative property. Probucol, a hydrophobic antioxidant drug, inhibits progression of atherosclerosis and post-angioplasty restenosis. However, the mechanism by which probucol affects atherosclerosis is not completely understood. Sixteen rabbits fed with high cholesterol diet for 8 weeks were randomly divided into two groups: (1) starch group (n = 8): maintained high cholesterol diet plus starch (500 mg/kg/d) for 6 weeks; (2) probucol group (n = 8): the same cholesterol diet plus probucol (500 mg/kg/d) for 6 weeks. Control group (n = 8) was fed with normal diet for 14 weeks. The classic in-situ two-step perfusion of the liver with collagenase IV was used to isolate the parenchymal hepatocytes. The total activity of superoxide dismutase (SOD) and malondialdehyde (MDA) and PON1 concentrations in serum were measured after 0, 8, and 14 weeks of feeding. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of PON1. Compared with control group, rabbits fed with high cholesterol diet showed higher levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), all of which were significantly reduced by probucol. Probucol significantly decreased the MDA concentration but was ineffective on SOD activity. High cholesterol diet decreased serum PON1 concentration and down-regulated PON1 mRNA expression in hepatocytes. Probucol significantly increased serum PON1 level and up-regulated the mRNA expression of PON1 as compared with starch group (0.65 +/- 0.06 versus 0.46 +/- 0.05, P = 0.001). The PON1 concentration is negatively associated with MDA concentration (r = -0.86, P = 0.003) but not with the level of HDL-C. In conclusion, probucol decreased MDA concentration, and increased PON1 serum level as well as mRNA expression in hepatocytes, which may help us to understand its antioxidant and anti-atherogenic effects.

Animals↗
PubMed2006

Atorvastatin reduces the expression of COX-2 mRNA in peripheral blood monocytes from patients with acute myocardial infarction and modulates the early inflammatory response.

BACKGROUND: We examined the effect of atorvastatin on the expression of COX-2 in peripheral blood monocytes from patients with early stage of acute myocardial infarction (AMI), and the plasma C-reactive protein (CRP) concentrations were also examined. METHODS: Patients with AMI (n = 40) and with stable coronary heart disease (CHD; n = 18) were registered, and patients with AMI were randomly separated to a group that received routine therapy (group A, n = 20) or to a group that received routine therapy plus atorvastatin at 20 mg/day (group B, n = 20) for a week. Peripheral blood monocytes from patients with AMI both before and after treatment and from patients with stable CHD were isolated and cultured for 24 h. COX-2 mRNA expression was analyzed by reverse transcription-PCR. We measured concentrations of CRP in plasma by ELISA. RESULTS: COX-2 expression was activated in peripheral blood monocytes from patients with AMI [0.92 (0.13)] compared with patients with stable CHD [0.19 (0.08)]; after a week of treatment, COX-2 expression in group B (reduced by 66%) was obviously lower than in group A (reduced by 24%; P <0.05). Plasma concentrations of CRP from patients with AMI [43.3 (14.9) mg/L] were increased compared with those from patients with stable CHD [1.65 (0.78) mg/L; P <0.05]; after a week of treatment, CRP concentrations in group B (reduced by 62%) were lower than in group A (reduced by 35%; P <0.05). COX-2 expression in peripheral blood monocytes from patients with AMI was positively correlated with plasma CRP concentration (r = 0.662; P <0.05). CONCLUSIONS: COX-2 may promote acute inflammatory process after AMI. Atorvastatin may improve the antiinflammatory effects through the COX-2 pathway.

Aged↗
PubMed2005

[Effects of atorvastatin on plasma hypersensitive C-reactive protein and interleukin-6 in patients with acute cerebral infarction].

OBJECTIVE: To observe the effects of different doses of atorvastatin on the plasma hypersensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with acute cerebral infarction. METHODS: 131 patients with acute cerebral infarction, 73 males and 58 females, aged 63 +/- 11, were randomly divided into 3 groups: Group A (n = 47), with basal treatment; Group B (n = 42), atorvastatin 10 mg was added every night; and Group C (n = 42), atorvastatin 20 mg was added every night. Before the treatment and 7 and 14 days after the treatment the plasma levels of hsCRP and IL-6, fasting plasma levels of lipid, such as total cholesterol (TC) and low density lipoprotein-C (LDL-C), liver functions, such as aspartate aminotransferase (ALT) and alanine transaminase (ALT), creatine kinase (CK), urea nitrogen, were detected. Neurological function deficit was determined. The survival condition was surveyed 6 months after. RESULTS: (1) The TC and LDL-C decreased after treatment in the 3 groups with significant differences between Group A and Group C, Group B and Group C, and Group B and Group C (all P < 0.05). (2) The plasma level of hsCRP decreased by 9.1%, 33.9%, and 30.1% respectively 7 days after treatment in Groups A, B, and C with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. The level of hsCRP decreased by 34.3%, 56.0%, and 52.9% respectively 14 days after treatment in the 3 groups with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. (3) The level of IL-6 decreased 7 and 14 days after treatment in all 3 groups, however, without significant differences between any 2 groups (all P > 0.05). (4) The decrease of hsCRP and decrease of IL-6 were not correlated with the percentage of TC decrease (both P > 0.05) in Group B. The decrease of hsCRP was not correlated with the changes of blood lipids in Group C. (5) Both the plasma hsCRP and IL-6 before treatment were positively correlated with the infection volume and neurological function score (all P < 0.01). CONCLUSION: Atorvastatin has an anti-inflammatory action benefiting the alleviation of secondary inflammatory damaged in acute cerebral infarction that is independent of lipid lowering.

Adult↗
PubMed2005

Atorvastatin reduces serum leptin concentration in hypercholesterolemic rabbits.

BACKGROUND: Leptin may play an important role in the development of atherosclerosis. We evaluated the effect of atorvastatin on leptin secretion in vivo and in vitro. METHODS: Sixteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) high cholesterol diet for 6 weeks (n=8), and (2) the same cholesterol diet plus atorvastatin (2.5 mg/kg/day) for 6 weeks (n=8). A control group (n=5) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for RNA analysis. The direct effect of atorvastatin on leptin release was assayed in primary rabbit adipocytes. Leptin levels in serum and adipocytes culture supernatant were measured by ELISA. RT-PCR was used to evaluate leptin mRNA expressions in adipose and adipocytes. RESULTS: Compared with control group, rabbits fed with high cholesterol diet showed higher levels of serum total cholesterol, LDL cholesterol and leptin, all of which were significantly reduced by atorvastatin treatment. Leptin mRNA expression of adipose was significant lower in rabbits treated with atorvastatin than those fed with high cholesterol diet continuously (0.81+/-0.31 vs. 1.23+/-0.36, P<0.05). Atorvastatin dose-dependently inhibited leptin secretion and mRNA expression in cultured adipocytes. CONCLUSION: Atorvastatin can inhibit leptin release and mRNA expression, and reduces serum leptin level in hypercholesterolemic rabbits.

Adipocytes↗
PubMed2005

Effect of atorvastatin on tumor necrosis factor alpha serum concentration and mRNA expression of adipose in hypercholesterolemic rabbits.

Tumor necrosis factor alpha (TNFalpha) is an inflammatory cytokine involved in atherogenesis. Adipose tissue is an important source of endogenous TNFalpha production. The aim of this study was to evaluate the effect of atorvastatin on TNFalpha serum concentration and mRNA expressions of subcutaneous adipose in hypercholesterolemic rabbits. Sixteen rabbits fed with a high-cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) the high-cholesterol group (n=8) was maintained on a high-cholesterol diet for 6 weeks; (2) the atorvastatin group (n=8) had the same high-cholesterol diet plus atorvastatin (2.5 mg/kg/d) for 6 weeks. A control group (n=5) was fed with a normal diet for 14 weeks. Subcutaneous adipose was collected for mRNA analysis. Additionally, the direct effect of atorvastatin on TNFalpha release and mRNA expression was assayed in primary rabbit adipocytes. TNFalpha levels in serum and adipocyte culture supernatant were measured by ELISA. RT-PCR was used to evaluate TNFalpha mRNA expression in adipose and adipocytes. Serum TNFalpha concentration was significantly associated with serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) (both P<0.01). Compared with the control group, rabbits fed with a high-cholesterol diet showed higher levels of TNFalpha serum concentration and mRNA expression of adipose, both of which were significantly reduced by atorvastatin treatment (both P<0.05). TNFalpha mRNA expressions of adipose were significantly correlated with circulating TNFalpha levels among the 3 groups (r=0.51, P<0.05). Atorvastatin dose-dependently inhibited lipopolysaccharide (LPS)-induced TNFalpha secretion and mRNA expression in cultured adipocytes. In conclusion, atorvastatin can directly inhibit TNFalpha expression and secretion in adipocytes. Atorvastatin reduced TNFalpha serum concentration in hypercholesterolemic rabbits, which might be because of its cholesterol-lowering effect and direct inhibition of TNFalpha expression in adipose.

Adipose Tissue↗
PubMed2005

[The effect of early fluvastatin therapy on inflammatory factors in acute coronary syndrome].

OBJECTIVE: To investigate the effects of different doses of fluvastatin on serum levels of high-sensitive C-reactive protein (hs-CRP) and tumour necrosis factor-alpha (TNFalpha) in the early phase of acute coronary syndrome (ACS). METHODS: Fifty eight patients with ACS were randomly separated into three groups. 20 patients in group A were given routine therapy, 20 patients in group B were given routine therapy with oral fluvastatin 40 mg once daily for 1 week and 18 patients in group C received routine therapy with oral fluvastatin 80 mg once daily for 1 week. 20 patients with stable coronary heart disease served controls. The serum levels of hs-CRP and TNFalpha before and after therapy were measured with immunoturbidimetric assay and ELISA method. RESULTS: (1) The serum levels of hs-CRP and TNFalpha in the patients with ACS were significantly higher than those in the control group (P < 0.05). (2) The serum levels of hs-CRP and TNFalpha significantly lowered after one week of therapy in the two fluvastatin treated groups (P < 0.01 in all), especially in the 80 mg fluvastatin group, while no significant difference was observed before and after treatment in the routine therapy group. (3) The serum levels of hs-CRP and TNFalpha had a significant positive correlation in the patients with ACS (r = 0.70, P < 0.01), but no relationship were observed between TC, TG, LDL-C, or HDL-C and hs-CRP or TNFalpha by Pearson correlation analysis. CONCLUSIONS: The serum levels of inflammatory factors including CRP and TNFalpha are increased in patients with ACS and early fluvastatin intervention may decease dose-dependently the serum levels of hs-CRP and TNFalpha. The anti-inflammatory effect of fluvastatin may be beyond that of lipid lowering. Early intensive fluvastatin treatment may yield more significant benefits in the patients with ACS.

Adult↗
PubMed2005

[Clinical observation and expression of C-reactive protein by LPS-induced A549 cells in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the level of mRNA expression of C-reactive proteins (CRP) induced by LPS in human alveolar type epithelial cell line, A549. METHODS: Sputum and plasma specimens were obtained from patients with chronic obstructive pulmonary disease (COPD) diagnosed according to the national criteria. CRP was measured by enzyme-linked immunosorbent assays (ELISA). A549 cells were incubated with lipopolysaccharide (LPS) at different concentrations and for different time. CRP mRNA was extracted from cells and the expression was analyzed by RT-PCR. The CRP in the supernatant was measured by ELISA. RESULTS: The concentration of CRP in the sputum of patients with COPD was significantly higher than that in the plasma (P < 0.05). LPS at different concentrations and for different time induced the expression and secretion of CRP in A549 with a time-dependent increase and the expression of CRP were significantly higher than those of the control (P < 0.05 - 0.01). CONCLUSION: Self-secretion of CRP in the respiratory tract may exist. A549 induced by LPS may express CRP mRNA.

C-Reactive Protein↗
PubMed2005

Effect of the interaction between paranoxonase 1 and ATP-binding cassette transporter 1 gene polymorphism on serum lipid level.

OBJECTIVE: To investigate the effect of interaction between paranoxonase 1 (PON1)gene polymorphism and ATP-binding cassette transporter 1 (ABCA1) genetic variation on serum lipid level. METHODS: Polymerase chain reaction-restricted fragments length polymorphism was used to determine PON1 A/B192 and ABCA1R219K genotype of 1019 subjects, including 680 patients with strokes and 339 healthy individuals as controls. RESULTS: No significant association between A/B192 genotype and any of the lipid measurements was detected. The levels of HDL-C in the subjects with RR, RK and KK genotypes showed a significant upward tendency respectively (P < 0.05); the levels of their triglyceride (TG) tended downward respectively, but there were no significant differences between them. The relationship between R219K genotype and serum lipid level was modified by A/B192 genotype. The levels of HDL-C in the subjects with AA/RR genotype and BB/KK genotype [(1.41 +/- 0.40) mmol/L, (1.41 +/- 0.39) mmol/L] were significantly different from that in the subjects with BB/RR genotype [(1.28 +/- 0.36) mmol/L] (P < 0.05). CONCLUSION: The result exhibited an interaction of PON1 A/B192 and ABCA1 R219K on serum lipid level.

ATP-Binding Cassette Transporters↗
PubMed2005

[Significance and expression of cyclooxygenase-2 mRNA in peripheral blood monocytes in patients with acute coronary syndrome].

OBJECTIVE: To determine the expression of cyclooxygenase-2 (COX-2) mRNA in peripheral blood monocytes in patients with acute coronary syndrome (ACS), and to explore the effect of the expression of COX-2 mRNA in ACS. METHODS: The expressions of COX-2 mRNA in peripheral blood monocytes from 18 normal subjects and 42 ACS patients were analyzed by reverse transcription polymerase chain reaction (RT-PCR), and the monocytes from patients were incubated with celecoxib in vitro. The concentrations of interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in supernates of monocytes were measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: The expression of COX-2 mRNA and the secrections of IL-6 and MMP-9 in peripheral blood monocytes in ACS patients significantly increased compared with those from normal controls [0.61 +/- 0.17 vs 0.11 +/- 0.09; (97.24 +/- 11.21) ng/L vs (22.15 +/- 6.30) ng/L; (41.20 +/- 8.41) g/L vs (11.76 +/- 4.23) g/L; all P < 0.05, respectively]. Celecoxib reduced IL-6 and MMP-9 secretion level of monocytes from ACS patients up to 48% and 50% respectively (all P < 0.05), in a concentration-dependent manner. CONCLUSION: COX-2 in peripheral blood monocytes may play an important role in the acute coronary syndrome.

Aged↗
PubMed2005

[The relationship between ApoE gene polymorphism and lipid parameters].

OBJECTIVE: To investigate the relationship between apolipoprotein E (ApoE) gene polymorphism and serum lipid profile. METHODS: Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine ApoE genotype on 1452 subjects including 1101 cases with cardio cerebrovascular disease including 379 cases with cerebral infarction, 313 cases with cerebral hemorrhage, 257 cases with coronary heart disease, and 152 cases with other types and on 351 healthy controls. RESULTS: After adjusting for age, sex and BMI, the subjects with ApoE4 carriers had significantly higher levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and ApoB than those with ApoE2 carriers and ApoE3/3 (P < 0.05), and higher level of triglyceride(TG) than those with ApoE3/3 (P < 0.05), while the subjects with ApoE2 carriers had significantly higher levels of high density lipoprotein-cholesterol (HDL-C) than those with ApoE4 (P < 0.05). The effects of ApoE polymorphism exhibited similarity in different sex and age of subjects. Linear regression analysis showed that unlike ApoE3/3, the HDL-C level in ApoE2 carriers tend upward with age (beta = 0.178, P = 0.015), significantly higher than ApoE4 carriers and ApoE3/3 in the cohort of 65-74 years (P < 0.05). The level of TC and TG in ApoE4 carriers had a tendency of downward with age (p = -0.179, P = 0.009; beta = -0.147, P = 0.032). CONCLUSION: ApoE gene polymorphism affected profile of blood lipids and the effects were found in different sex and age. The degrees of effects related to ApoE2 carriers and ApoE4 carriers to blood lipid level seemed to be related to age.

Adult↗