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ABSTRACT: Remnant-like lipoproteins (RLPs) have been demonstrated to accelerate the onset of endothelial progenitor cells (EPCs) senescence. Recent study has determined that microRNAs (miRNAs) were closely associated with cellular proliferation and senescence. This study aimed to examine whether RLPs lead to an alteration of miRNAs in senescent EPCs.
RLPs were prepared from plasma samples with immunoaffinity method. After 8 days of culture, EPCs were identified by flow cytometry analysis. Cells were incubated with RLPs for 72 hours. The senescent markers p16INK4a and senescence-associated beta-galactosidase (SA-β-gal) were detected by Western blotting analysis and β-gal staining assay, respectively. A human miRNA microarray containing 723 miRNAs was used to detect the expression profile of miRNAs in control and senescent EPCs. The result from the above microarray was qualified by RT-PCR assay.
RLPs dose-dependently up-regulated the protein level of p16(INK4a) in EPCs, and RLPs at a concentration of 100 µg/ml induced a significant increase in the percentage of SA-β-gal-positive EPCs. Of 723 miRNAs, four miRNAs expressed differentially and significantly in RLPs-treated EPCs (P < 0.05), then their changes in expression were validated by real-time RT-PCR. Among them miR-148b and miR-155 were upregulated while miR-574-3p was down-regulated significantly when compared with control (P < 0.01).
RLPs result in the onset of EPCs senescence. Senescent EPCs induced by RLPs exhibit a different profile of miRNAs. These three miR-148b and miR-155 and miR-574-3p reach a significant difference when compared with control, indicating that microRNA might take part in RLPs-induced EPCs senescence.
Chinese medical journal 10/2012; 125(19):3479-84. · 0.86 Impact Factor
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ABSTRACT: Apolipoprotein A5 (apoA5), an important determinant of plasma triglyceride (TG) levels, has been recently reported to modulate TG metabolism in hepatocytes. In this study, we investigated whether apoA5 can be internalized by adipocytes and regulate cellular TG storage. Human preadipocytes, derived from subcutaneous adipose tissue of patients undergoing abdominal surgery, were differentiated into mature adipocytes. Pulse-chase experiments revealed that apoA5 was internalized into human adipocytes, and ∼70% of the apoA5 internalized during the pulse remained intracellular within a 24-h chase, while 30% was degraded. Preincubation with heparin and the receptor-associated protein, both of which prevented the apoA5 interaction with members of the low-density lipoprotein receptor gene family, markedly reduced the uptake of apoA5 by 61% and 52%, respectively, which were subsequently confirmed by Western blot analysis. Using confocal microscopy, we demonstrated that labeled apoA5 surrounded lipid droplets in human adipocytes and colocalized with the known lipid droplet protein perilipin. Importantly, treatment of adipocytes with apoA5 significantly decreased cellular TG storage. In conclusion, apoA5 can be internalized by human adipocytes and may act as a novel regulator to control TG storage in human adipocytes.
Biological Chemistry 02/2012; 393(3):161-7. · 2.96 Impact Factor
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ABSTRACT: We previously found that remnant-like lipoproteins (RLPs), lipolytic products of triglyceride-rich lipoproteins including very low-density lipoprotein and chylomicron, can accelerate endothelial progenitor cell (EPC) senescence, which involves telomerase activity. The aim of this study was to investigate the effects of RLPs on telomerase activity and the catalytic subunit telomerase reverse transcriptase (TERT) in EPCs and the associated signal pathway.
RLPs were prepared from plasma samples by the immunoaffinity method. EPCs at day 8 were incubated with RLPs at 10-, 50-, 100-, and 200-μg/mL for 24 hours. Telomerase activity was measured with telomeric repeat amplification protocol assay, and optimum concentration of RLPs was determined. Human TERT (hTERT) and phosphorylated Akt protein kinase were detected by Western blot analysis in RLP-incubated EPCs with or without pretreatment of either superoxide dismutase or atorvastatin for 3 hours. Phosphorylated hTERT was measured by immunoprecipitation and Western blot assay. Nitrotyrosine was evaluated by immunofluorescence assay, and senescent EPCs were determined by senescence-associated β-galactosidase staining.
Dose dependently, RLPs resulted in a decrease in telomerase activity, with a maximal effect at 200 μg protein/mL. The optimum concentration of RLPs was determined as 100 μg protein/mL. This dosage resulted in significant increases in senescence-associated β-galactosidase-positive cell and nitrotyrosine staining. In addition, RLPs decreased the expression of hTERT and repressed the phosphorylation of Akt and hTERT. Pretreatment of either superoxide dismutase or atorvastatin remarkably reversed these effects.
RLPs may suppress telomerase activity and accelerate EPC senescence through downregulating hTERT expression via the reactive oxygen species-dependent pathway.
The Canadian journal of cardiology 07/2011; 27(5):628-34. · 3.36 Impact Factor
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ABSTRACT: Cellular senescence is a program activated in normal cells in response to various types of stresses and is manifested by permanent arrest of cell cycle. Cellular senescence is closely related to tumor suppression, and may contribute to the ageing of organisms. The complex senescence cell phenotype has many different mechanisms. Recent studies have provided important insights regarding the role played by miRNAs during cellular senescence as a novel molecular mechanism. In this article, we will review the latest advances in the identification and validation of senescence-regulatory miRNAs and the possible mechanisms.
Ageing research reviews 06/2011; 11(1):41-50. · 5.62 Impact Factor
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ABSTRACT: To investigate the effects of estrogen treatment on aortic endothelial senescence and atherosclerosis, an ovariectomized female rabbit model was constructed, and human umbilical vein endothelial cells were utilized to explore the potential mechanisms. Twenty-eight female rabbits were randomized into 4 groups (7 each): sham operation, ovariectomized, ovariectomized plus low-dose estradiol treatment, and ovariectomized plus high-dose estradiol treatment. All rabbits were fed on high-cholesterol diet for 12 weeks. Blood samples were collected to determine the serum estradiol, asymmetric dimethyl L-arginine (ADMA), and lipid levels, and the aortas were separated for histopathologic analysis. After ovariectomy and high-fat diet, the concentration of serum estradiols declined significantly (P < 0.01) and the levels of ADMA and serum lipids increased (all P < 0.01) as the area of senescent endothelium and atherosclerotic lesions enlarged (both P < 0.01). However, administration of estradiols reduced the levels of ADMA, total cholesterol, and low-density lipoprotein (LDL) cholesterol and inhibited endothelial senescence and atherosclerosis (all P < 0.01). Simultaneously, the concentration of high-density lipoprotein cholesterol and triglyceride increased (all P < 0.01). In vitro experiments also confirmed that estradiols could decrease the ADMA levels induced by oxidized LDL and inhibited oxidized LDL–induced and ADMA-induced human umbilical vein endothelial cell senescence. These results indicate that estrogens can inhibit endothelial senescence and atherosclerosis with reduced ADMA levels and improved lipid profile.
Journal of cardiovascular pharmacology 11/2010; 57(2):174-82. · 2.83 Impact Factor
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ABSTRACT: To investigate the effect of soluble epoxide hydrolase inhibitor (sEHi) tAUCB on the function of endothelial progenitor cells (EPCs) and expression of vascular endothelial growth factor (VEGF) in EPCs in patients with coronary heart disease (CHD).
Mononuclear cells, from the peripheral blood of CHD patients, were isolated by ficoll density gradient centrifugation and cultured. After 7 days of culture in vitro, EPCs were identified by double staining and flow cytometry. EPCs were then stimulated by 0, 10(-6), 10(-5), and 10(-4) mol/L of tAUCB for 24 h. Migration assay was performed in transwell chamber and tube formation assay was performed by Matrigel-Matrix in vitro model. The expression of VEGF in EPCs was measured by Western blot. EPCs from age and gender matched healthy subjects were also cultured as controls.
The migration and tube formation activities of EPCs from CHD patients were obviously damaged compared with those from healthy controls (P<0.05). The tAUCB could dose-dependently increase the migration and tube formation activities and increase the expression of VEGF in EPCs compared with those from CHD patients without treatment. The 10(-6) mol/L tAUCB increased those activities of EPCs and the expression of VEGF with statistical difference.
sEHi can positively modulate the function of EPCs from CHD patients, suggesting the potential predictive significance of sEHi in the therapy of CHD.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 07/2010; 35(7):685-92.
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ABSTRACT: To compare the lipid lowing effect and the clinical safety between intensive therapy with Chinese medicine Zhibitai and atorvastatin in patients with moderate and high risk of atherosclerosis.
All the patients were randomly divided in to a Zhibitai group (n = 85) receiving 480 mg of Zhibitai orally twice a day or an atorvastatin group (n = 84) receiving 10 mg atorvastatin orally once daily. Blood lipoproteins, myocardial enzymes, liver and renal function were measured before treatment and at the fourth and eighth week after therapy, while high sensitive c reactive protein (hs-CRP), P-selectin, matrix-metall proteinase-9 (MMP-9) and soluble intercellular adhering molecule-1 (SICAM-1) were detected before treatment and eighth week after therapy in all patients.
TC and LDL-C were significantly decreased while HDL-C was increased in both groups after 4 and 8 weeks treatment (P < 0.05). TG was decreased in Zhibitai group after 4 and 8 weeks of treatment, but it was decreased in atorvastatin group only after 8 weeks of treatment. Inflammatory factors such as hs-CRP, P-selectin, MMP-9, SICAM-1 were decreased significantly (all P < 0.01), but there was no significant difference between the two groups. There were no difference in liver and kidney function, myocardial enzymes and incidence of muscle-ache and digestive system side reaction.
Besides the lipoprotein disorder, inflammatory factors in patients with moderate and high risk of atherosclerosis could be regulated with intensive therapy of Zhibitai. Most importantly, it is safe to use Zhibitai clinically.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 05/2010; 49(5):392-5.
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ABSTRACT: To investigate the effects of Glimepiride on blood glucose in patients with newly diagnosed type 2 diabetes mellitus (T2DM) in connection with plasma lipoproteins and plasminogen activity.
A total of 565 T2DM patients were received Glimepiride (n=333) or Glibenclamide (n=232) for 12 weeks. We observed the level of blood glucose (BG), glycated hemoglobin (HbA1C), the insulin resistance (IR) state, plasma lipoproteins, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type I (PAI-1) before and after a 12 weeks of treatment.
After 12 weeks with Glimepiride treatment, significant reductions were observed in fasting blood glucose (FBG) and 2-h postprandial BG(PBG), HbA1C (from 8.60+/-3.10 to 7.10+/-1.60%) and HOMA-IR (from 4.11+/-0.85 to 2.42+/-0.91%). The level of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly decreased, whereas that of high-density lipoprotein (HDL) was increased markedly with statistical significance. In addition, there was an obvious improvement in t-PA activity (from 0.225+/-0.11 to 0.457+/-0.177IU/ml); whereas the PAI-1 activity was decreased significantly (from 0.898+/-0.168 to 0.533+/-0.215AU/ml). No significant changes were observed in plasma lipoprotein profiles and plasminogen activity in Glibenclamide receiving group.
Glimepiride can rapidly and stably improve glycemic control and lipoprotein metabolism, significantly alleviate insulin resistance and enhance fibrinolytic activity.
Diabetes research and clinical practice 04/2010; 88(1):71-5. · 2.16 Impact Factor
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ABSTRACT: To evaluate the lipid lowering ability, anti-inflammatory effects and clinical safety of intensive therapy of the Chinese traditional medicine Zhibitai in subjects with moderate to high cardiovascular risk.
A total of 169 subjects (96 males and 73 females, aged 55-72) having moderate to high cardiovascular risk were recruited and randomly divided into Zhibitai group (n=85), which received 480 mg of Zhibitai orally twice daily, and atorvastatin group (n=84), which received 10 mg of atorvastatin orally once a day. Blood lipoproteins, myocardial enzymes, liver and renal functions were measured before treatment started, and after 4 and 8 weeks of the treatment. High sensitivity C-reactive protein (hs-CRP), P-selectin, matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured before and after the treatment.
Plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly decreased, and high-density lipoprotein cholesterol (HDL-C) was increased in both groups, after 4 and 8 weeks of treatment (p<0.05 for all pairs). Interestingly, plasma triglycerides (TG) decreased in the Zhibitai group after 4 weeks of treatment but only decreased in the atorvastatin group after 8 weeks. Inflammatory factors such as hs-CRP, P-selectin, MMP-9 and sICAM-1 were significantly decreased in both groups after 8 weeks (p<0.01 for all pairs). Furthermore, there was no difference in myocardial enzymes, hepatic and renal function test parameters, incidence of myopathy or gastrointestinal tract symptoms in either group.
Zhibitai therapy is a good alternative to statin therapy to reduce plasma cholesterol levels in subjects with moderate to high cardiovascular risk. Most importantly, Zhibitai is safe to use.
Atherosclerosis 02/2010; 211(1):237-41. · 3.79 Impact Factor
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ABSTRACT: To evaluate the effects of combined atorvastatin and probucol use on endothelial function in patients with acute coronary syndrome (ACS).
Thirty patients with ACS were randomized to receive atorvastatin (20 mg/d) and probucol (500 mg/d, combination group, n = 15) or atorvastatin (20 mg/d) alone (atorvastatin group) within 24 h after admission for 4 weeks. Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent sublingual nitroglycerin-mediated dilatation (NMD) as well as the levels of lipids and C-reactive protein were assessed at baseline, 1 week and 4 weeks after therapy.
Compared to baseline, the levels of total cholesterol, LDL-C and C-reactive protein were significantly reduced after 1 week and 4 weeks in both groups, FMD equally increased after 1 week in both groups (atorvastatin group: 3.75% +/- 0.78% vs. 1.09% +/- 0.44%, combination group: 3.67% +/- 0.36% vs. 1.24% +/- 0.37%, P < 0.01). Post 4 weeks therapy, FMD increase was significantly higher in combination group (3.67% +/- 0.36% at 1 week vs. 6.85% +/- 0.64% at 4 weeks, P < 0.01) than that in atorvastatin group (3.75% +/- 0.78% vs. 3.80% +/- 0.31%, P = 0.954). NMD also equally and increased over 4 weeks in two groups (P < 0.01 vs. baseline). There was no correlation between the change in FMD/NMD and the changes in lipids or C-reactive protein levels.
The combined atorvastatin and probucol therapy early after ACS is superior to atorvastatin alone on improving endothelial function.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 10/2009; 37(10):900-3.
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ABSTRACT: Endothelial dysfunction induced by various atherosclerotic risk factors can initiate the process of atherosclerosis. Endothelial progenitor cells (EPCs), which have been considered as the precursor of endothelial cells (ECs), play an important role in the maintenance of endothelial function. The inverse association between high-density lipoprotein (HDL) levels and the risk of coronary heart disease (CHD) events has been demonstrated. Furthermore, accumulating studies suggest an important role of HDL in preventing and restoring endothelial dysfunction. Also, the importance of apolipoprotein A-I (apoA-I) in protection against cardiovascular disease is widely researched. Recently, it is shown that HDL could protect cultured human EPCs in different ways. Here, we review the studies on the association between HDL, its functional components, including apoA-I and mimetic peptide, and endothelial function and the underlying mechanisms that have been carried out so far.
International journal of cardiology 01/2009; 133(3):286-92. · 7.08 Impact Factor
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ABSTRACT: Inflammation plays a pivotal role in the pathophysiology of atherosclerosis. Remnant-like lipoprotein particles (RLPs) have been implicated as potentially atherogenic lipoproteins. RLPs can induce a pronounced inflammatory response especially during the postprandial phase. Increasing evidence demonstrates that adipose tissue may be a significant contributor to the increased systemic inflammation through secretion of various proinflammatory adipocytokines. In addition, adipocytes may potentially regulate RLPs metabolism. Therefore, we hypothesized that there might be an interaction between RLPs and adipocytes.
International journal of cardiology 12/2008; 133(1):3-7. · 7.08 Impact Factor
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ABSTRACT: To explore the relationship of apolipoprotein E (ApoE) genotype with hypertriglyceridemia-associated recurrent acute pancreatitis.
Taking the fasting serum triglyceride (TG) level > or = 2.3 mmol/L as hypertriglyceridemia, ApoE genotypes in 115 patients with hypertriglyceridemia-associated recurrent acute pancreatitis were assessed by polymerase chain reaction. According to the fasting serum TG level, all patients were divided into 3 groups: TG mild elevation group (2.3 mmol/L < or = TG < 5.5 mmol/L, Group A), TG moderate elevation group (5.5 mmol/L < or = TG < 11.3 mmol/L, Group B), and TG severe elevation group (TG > or = 11.3 mmol/L, Group C).
Group C had significantly fewer patients with biliary tract disease, improper diet and heavy alcohol consumption, and significantly more patients with passed history of moderate-severe hypertriglyceridemia than Group A and B (P < 0.05). The proportion of patients with E3/4, E3/2, E2/4 and E2/2 genotypes and gene frequency for epsilon 2 and epsilon 4 alleles are significantly higher in Group C than in Group A and B(P < 0.05). Group B had significantly more patients with E3/2 genotype and higher gene frequency for epsilon 2 allele than Group A (P < 0.05).
Apo epsilon 2 and epsilon 4 alleles are closely related to moderate-severe hypertriglyceridemia-associated recurrent acute pancreatitis.
Zhonghua wai ke za zhi [Chinese journal of surgery] 11/2008; 46(20):1579-82.
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ABSTRACT: To explore the effect of valsartan on the concentrations of plasma inflammatory factors after a high-fat meal in patients with essential hypertension in very short time.
Fifty hypertensive patients and 25 healthy controls were studied. Patients randomly accepted lacidipine 4 mg/d (lacidipine group) or valsartan 80 mg/d (valsartan group) for 1 week. The concentrations of plasma lipid profiles, high-sensitivity C-reactive protein (hsCRP) and soluble P-selectin were measured in fasting state and at 4 h after a single high-fat meal in all subjects at baseline and in patients after 1 week.
The concentrations of postprandial plasma hsCRP and soluble P-selectin significantly increased after a high-fat meal in patients (P < 0.05), as compared with those at fasting levels, but not in the controls. The postprandial plasma triglyceride concentrations significantly increased in the healthy controls (P < 0.05), but were lower than those in hypertensive patients (P < 0.01). Postprandial change in plasma concentration of triglyceride was significantly correlated with those of log (hsCRP) (r = 0.344)and soluble P-selectin (r = 0.432), respectively (n = 75, both P < 0.01). Lipids profiles did not change significantly after 1 week. There was no significant difference between the fasting and postprandial plasma concentrations of either hsCRP or soluble P-selectin in valsartan group, while the postprandial increments of inflammatory factors were still significant in the lacidipine group.
High-fat meal can induce postprandial inflammation response in patients with essential hypertension. Valsartan effectively attenuates this postprandial inflammation response within a very short time.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 09/2008; 33(9):809-13.
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ABSTRACT: Endothelial cells (ECs) damage is an initial and pivotal step in the formation of atherosclerosis. Endothelial progenitor cells (EPCs), which have been considered as the precursor of ECs, can migrate and home to the site of injured ECs to divide into mature ECs and keep the integrity of the endothelial monolayer. It has been shown that the number and function of EPCs are negatively correlated with various atherosclerotic risk factors. This finding may be explained partly by accelerated senescence of EPCs induced by telomere attrition or shortening owning to oxidative stress and accumulative ROS. However, elevated telomerase activity which extends the telomere cannot lead to cellular immortal in the presence of the cyclin-dependent kinase inhibitor p16(INK4a). Researchers have the opinion that senescence is the balance between the regeneration and cancer. High expression of phosphorylated p16(INK4a), which is caused by oxidative stress and accumulative ROS, can prevent tumor cells from unlimited division and becoming malignant ones by accelerating premalignant cells premature senescence. It has been demonstrated that the expression of p16(INK4a) increases remarkably with age due to oxidative stress and accumulative ROS in some stem and progenitor cells, and regulates these cells age-dependent senescence. It is observed that telomeres shortening exists in these cells. Therefore, it can be hypothesized that p16(INK4a), together with telomerase, may co-modulate EPCs senescence.
Ageing Research Reviews 05/2008; 7(2):137-46. · 6.17 Impact Factor
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ABSTRACT: To investigate the changes of inflammatory factors and hemostatic variable in plasma after a high-fat meal in normocholesterolemic patients with essential hypertension.
A total of 60 hypertensive patients were randomly assigned to accept a single high-fat meal (group 1, n=40) or not (group 2, n=20) in the morning after an overnight fast, and 20 healthy participants (group 3) consumed a single high-fat meal on the same day. Plasma lipid profiles, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFalpha), soluble P-selectin and plasminogen activator inhibitor type 1 (PAI-1) antigen levels were measured at fasting and 4 h after meal ingestion.
Postprandial triglyceride levels increased significantly in groups 1 and 3 (P<0.01), whereas levels were higher in group 1 (P<0.001). Postprandial plasma TNFalpha, hsCRP, soluble P-selectin and PAI-1 antigen levels increased in group 1 (P<0.001) but not in group 3. Postprandial plasma triglyceride level was correlated with log(hsCRP) (P<0.001), TNFalpha (P<0.001), soluble P-selectin (P<0.01) and PAI-1 antigen (P<0.05) levels, respectively. Both postprandial plasma level of soluble P-selectin and that of PAI-1 antigen were positively and significantly correlated with those of log(hsCRP) (P<0.01) and TNFalpha (P<0.001), respectively.
Postprandial hypertriglyceridemia in hypertensive patients is associated with inflammatory response and procoagulant state.
Coronary Artery Disease 05/2008; 19(3):145-51. · 1.24 Impact Factor
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ABSTRACT: Remnant-like particles (RLPs) are closely associated with coronary heart disease and can induce endothelial dysfunction through oxidative mechanisms. Many risk factors accelerate the onset of endothelial progenitor cells (EPCs) senescence via increased oxidative stress. In this study, we investigated the effect of RLPs on EPCs senescence and function. RLPs were isolated from postprandial plasma of hypertriglyceridemic patients by use of the immunoaffinity gel mixture of anti-apoA-1 and anti-apoB-100 monoclonal antibodies. Our results show that EPCs became senescent as determined by senescence-associated acidic beta-galactosidase (SA-beta-Gal) staining after ex vivo cultivation without any stimulation. Co-incubation with RLPs accelerated the increase in SA-beta-Gal-positive EPCs. The acceleration of RLPs-induced EPCs senescence occurred dose-dependently with a maximal effect when EPCs were treated with RLPs at 0.10 mg cholesterol/mL (P<0.01). Moreover, RLPs decreased adhesion, migration and proliferation capacities of EPCs as assessed by adherence to fibronectin, modified Boyden chamber technique and MTT assay (P<0.01), respectively. RLPs increased nitrotyrosine staining in EPCs. However, RLPs-induced EPCs senescence and dysfunction were significantly inhibited by pre-treatment of superoxide dismutase (50 U/mL) (P<0.05). Our results provide evidence that RLPs accelerate the onset of EPC senescence via increased oxidative stress, accompanying with the impairment of adhesion, migration and proliferation capacities.
Atherosclerosis 05/2008; 202(2):405-14. · 3.79 Impact Factor
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ABSTRACT: Numerical and functional impairment of circulating endothelial progenitor cells (EPCs) is thought to contribute to endothelial dysfunction and the associated increase in cardiovascular risk. Increased EPCs number and activity are associated with the inhibition of EPCs senescence, which involved activation of telomerase. Telomerase activity can be regulated by phosphatidylinositol-3-kinase/Akt (PI3K/Akt) signaling pathway which also modulates the activity of endothelial nitric oxide synthase (eNOS). Increased oxidative stress induces telomerase inactivity whereas nitric oxide (NO) can reduce oxidative stress, thus activates telomerase. Plasma high-density lipoprotein (HDL) cholesterol levels have an inverse correlation with incidence of ischemic heart disease as well as other atherosclerosis-related ischemic conditions. However, the exact mechanism by which HDL prevents ischemic disease is not fully understood. HDL not only increases NO by activating eNOS through PI3K/Akt signaling pathway, but also directly stimulates EPCs differentiation via PI3K/Akt pathway. Moreover HDL can increase circulating EPCs number and enhances ischemia-induced angiogenesis. On the basis of recent findings, this manuscript proposed a new hypothesis that HDL could against atherosclerotic cardiovascular disease partially through slowing down EPCs senescence by increasing NO and promoting telomerase activity via PI3K/Akt signaling pathway.
Medical Hypotheses 02/2008; 70(2):338-42. · 1.39 Impact Factor
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ABSTRACT: Remnant-like lipoprotein particles (RLPs) have been implicated as potentially atherogenic lipoproteins. Endothelial dysfunction is known to be an early event in atherosclerosis and an important contributor to the pathogenesis of coronary artery disease. Moreover, there is considerable evidence linking increased RLP cholesterol levels with endothelial dysfunction, reflected by impaired endothelial vasodilatation and abnormal endothelial secretion. The underlying mechanisms by which RLPs may contribute to endothelial dysfunction are complex and have not been completely elucidated. Because the expression and activation of endothelial nitric oxide synthase (eNOS) are vital to endothelial function, and recent data have implied an association between RLPs and eNOS, this manuscript proposes the hypothesis that RLPs could impair endothelial function via direct and indirect effects on eNOS: RLPs may affect the autophosphorylation of focal adhesion kinase and its downstream phosphatidylinositol kinase/Akt (protein kinase B) signaling pathway, resulting in eNOS inactivation through induction of intracellular oxidative stress in endothelial cells; and RLPs could affect the expression or activation of eNOS indirectly by stimulating secretion of various inflammatory factors from multiple origins. The practical applications of this manuscript provide new insights for the future investigation of RLPs.
The Journal of Lipid Research 09/2007; 48(8):1673-80. · 5.56 Impact Factor
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ABSTRACT: The postprandial state is critical in atherogenesis. The aims of this study were to study the postprandial change of plasma high-sensitivity C-reactive protein (hsCRP) concentrations in patients at high risk for cardiovascular events, and to explore the influence of fluvastatin on hsCRP concentration.
Forty-three patients at high risk for cardiovascular events and 15 healthy controls participated in this study. All participants received an oral high-fat meal (800 calories; 50 g fat) at baseline. Blood samples were drawn at 0 and 4 h to measure the plasma concentrations of triglyceride, total cholesterol, low-density and high-density lipoprotein cholesterol and hsCRP. Then patients at high risk were randomly divided into two groups to accept fluvastatin (40 mg/day) (fluvastatin group, n=22) or placebo (placebo group, n=21). One week later, the high-fat meals were repeated and plasma samples were collected again.
The postprandial plasma triglyceride concentrations increased in all participants, whereas the postprandial plasma hsCRP concentrations increased significantly only in patients at high risk (P<0.05), but not in healthy controls. After 1 week, the fasting or postprandial plasma lipid levels and hsCRP concentrations did not significantly change in the placebo group compared with the levels at baseline, whereas the postprandial plasma triglyceride and hsCRP concentrations significantly decreased in the fluvastatin group. The reduction of plasma hsCRP concentration was not related to the change of plasma triglyceride concentration.
Fluvastatin effectively reduced postprandial plasma hsCRP concentrations in patients at high risk for cardiovascular events in a very short period of time.
Coronary Artery Disease 09/2007; 18(6):489-93. · 1.24 Impact Factor
