The Presence of Blastocystis in Tibetan Antelope (Pantholops hodgsonii).

Blastocystis is a protozoan that parasitizes the intestines. A number of hosts of Blastocystis have been found, including human and animals. However, there has been no research on the prevalence of Blastocystis in Tibetan antelope. Here, a molecular test was performed using 627 Tibetan antelope fecal samples collected on Tibet in China from 2019 to 2020. The result showed that 30 (4.8%) samples were Blastocystis positive. The highest prevalence of Blastocystis was in Shuanghu County (25/209, 12.0%), followed by Shenza County (2/103, 1.9%), Nyima County (3/182, 1.6%), and Baigoin County (0/133, 0.0%). In addition, logistic regression analysis showed that the gender, sampling year, and area of Tibetan antelope were risk factors for Blastocystis prevalence. Three subtypes (ST10, ST13, and ST14) of Blastocystis were found in Tibetan antelope through a subtype sequence analysis, and ST13 was identified to be the dominant subtype. This is the first investigation for the infection of Blastocystis in Tibetan antelope. Collectively, the data in this study have expanded the host range of Blastocystis and provided basic information for the distribution of Blastocystis subtypes, which could support the prevention of Blastocystis infection in wild animals.

Prevalence and Characterization of Cryptosporidium Species in Tibetan Antelope (Pantholops hodgsonii).

Cryptosporidium is an enteric apicomplexan parasite, which can infect multiple mammals including livestock and wildlife. Tibetan Antelope (Pantholops hodgsonii) is one of the most famous wildlife species, that belongs to the first class protected wild animals in China. However, it has not been known whether Tibetan Antelope is infected with Cryptosporidium so far. The objective of the present study was to determine the prevalence and characterization of Cryptosporidium species infection in Tibetan Antelope and the corresponding species by using molecular biological method. In the current study, a total of 627 fecal samples were randomly collected from Tibetan Antelope in the Tibet Autonomous Region (2019-2020), and were examined by PCR amplification of the small subunit ribosomal RNA (SSU rRNA) gene. Among 627 samples, 19 (3.03%, 19/627) were examined as Cryptosporidium-positive, with 7 (2.33%, 7/300) in females and 12 (3.67%, 12/327) in males. The analysis of SSU rRNA gene sequence suggested that only two Cryptosporidium species, namely, C. xiaoi and C. ubiquitum, were identified in this study. This is the first evidence for an existence of Cryptosporidium in Tibetan Antelope. These findings extend the host range for Cryptosporidium spp. and also provide important data support for prevention and control of Cryptosporidium infection in Tibetan Antelope.

Prevalence and Risk Factors of Brucellosis, Toxoplasmosis, and Neosporosis Among Yanbian Yellow Cattle in Jilin Province, China.

Brucellosis and Toxoplasmosis are important zoonotic diseases, and Neospora caninum is a parasite causing disease in cattle and other animals. Brucella spp. and N. caninum can cause abortions in cattle, and Toxoplasmosis is a relevant cause of abortion for small ruminants, resulting in economic loses to farmers. In this study, from July 2015 to April 2017, a total of 535 Yanbian yellow cattle blood samples were collected from 3 cities in Jilin Province, China. We detected the frequency of N. caninum, Toxoplasma gondii, and Brucella spp. using enzyme-linked immunosorbent assays, indirect hemagglutination assay, and real-time PCR methods, respectively. The frequency of Brucella was 7.7% (41/535), and the seroprevalences of N. caninum and T. gondii were 6.2% (33/535) and 5.0% (27/535), respectively. The region, gender, and age of Yanbian yellow cattle were considered as risk factors when analyzed using a logistic regression model. These findings provide the foundation for the prevention and control of infection by these pathogens in Yanbian yellow cattle and humans.

Paracrine effects of bone marrow-derived endothelial progenitor cells: cyclooxygenase-2/prostacyclin pathway in pulmonary arterial hypertension.

BACKGROUND: Endothelial dysfunction is the pathophysiological characteristic of pulmonary arterial hypertension (PAH). Some paracrine factors secreted by bone marrow-derived endothelial progenitor cells (BMEPCs) have the potential to strengthen endothelial integrity and function. This study investigated whether BMEPCs have the therapeutic potential to improve monocrotaline (MCT)-induced PAH via producing vasoprotective substances in a paracrine fashion. METHODS AND RESULTS: Bone marrow-derived mononuclear cells were cultured for 7 days to yield BMEPCs. 24 hours or 3 weeks after exposure to BMEPCs in vitro or in vivo, the vascular reactivity, cyclooxygenase-2 (COX-2) expression, prostacyclin (PGI2) and cAMP release in isolated pulmonary arteries were examined respectively. Treatment with BMEPCs could improve the relaxation of pulmonary arteries in MCT-induced PAH and BMEPCs were grafted into the pulmonary bed. The COX-2/prostacyclin synthase (PGIS) and its progenies PGI2/cAMP were found to be significantly increased in BMEPCs treated pulmonary arteries, and this action was reversed by a selective COX-2 inhibitor, NS398. Moreover, the same effect was also observed in conditioned medium obtained from BMEPCs culture. CONCLUSIONS: Implantation of BMEPCs effectively ameliorates MCT-induced PAH. Factors secreted in a paracrine fashion from BMEPCs promote vasoprotection by increasing the release of PGI2 and level of cAMP.

[Effects of proton pump inhibitors on in-stent restenosis in patients receiving clopidogrel: a retrospective analysis].

OBJECTIVE: To determine the effect of proton pump inhibitor (PPI) on in-stent restenosis (ISR) in patients receiving clopidogrel therapy. METHODS: Total 439 patients underwent percutaneous coronary intervention (PCI) were enrolled in the study,including 250 post-PCI patients discharged on clopidogrel alone and 189 patients discharged on clopidogrel with PPI. The in-stent restenosis (ISR) ratio of the patients in these two groups were observed. RESULTS: During a mean follow-up period of (13 ± 5.9) months, the post-PCI patients discharged on concomitant clopidogrel-PPI therapy had higher risk of ISR than those discharged on clopidogrel alone (19.6% Compared with 8%, P<0.001). CONCLUSION: Concomitant use of clopidogrel and PPI after hospital discharge would increase the risk of ISR for post-PCI patients.

Resveratrol attenuates apoptosis of pulmonary microvascular endothelial cells induced by high shear stress and proinflammatory factors.

Endothelial injury usually underlies the initial pathologic step of cardiovascular diseases. Primary endothelial cell (EC) apoptosis and secondary hyperproliferation both contribute to the development of atherosclerosis and luminal occlusion. In order to investigate the effects of resveratrol (RSV) on EC apoptosis, we applied high shear stress (HSS) with proinflammatory factors [tumor necrosis factor alpha (TNF-α) plus cycloheximide] to human pulmonary microvascular ECs (PMVECs) through an artificial capillary system. Intracellular reactive oxygen species (ROS) was measured by spectrofluorometry using dihydrorhodamine 123 fluorescent probe. Apoptosis and proliferation was determined by flow cytometric analysis. Protein expression was examined by Western blot. HSS plus inflammation significantly raised the ROS and the apoptosis level of PMVECs, which could be diminished by RSV pretreatment. In a 7-days incubation assay, RSV effectively inhibited the initial increase in apoptosis and thereby prevented subsequent PMVEC hyperproliferation induced by HSS plus inflammation. Mercaptosuccinate, a glutathione peroxidase (GPx-1) inhibitor or nicotinamide, a silent information regulator 2/sirtuin 1 (SIRT1) inhibitor could attenuate the antiapoptotic action of RSV on PMVECs; and RSV treatment upregulated GPx-1 and SIRT1 expression in PMVECs. In conclusion, RSV, probably by activating SIRT1 signaling pathway, inhibits the oxidative-stress-dependent phenotypical shift of ECs induced by HSS and proinflammatory factors in vitro.

Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca(2+)-cycling proteins in streptozotocin-induced diabetic rats.

To investigate the influence of breviscapine on the cardiac structure and function in diabetic cardiomyopathy rats as well as the expression of protein kinase C (PKC) and Ca(2+)-cycling proteins expression. Diabetes was induced in male Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin and the control rats were injected with saline. After the induction of diabetes for 4 weeks, the animals were divided into different groups: (1) normal rats as control; (2) diabetic rats; (3) diabetic rats with administration of breviscapine (10 or 25 mg kg(-1) day(-2)). After treatment with breviscapine for 6 weeks, the invasive cardiac function and echocardiographic parameters were measured, and heart tissue was obtained for electron microscope study. The expression of protein kinase C (PKC) and calcium handling regulators, such as protein phosphatase inhibitor-1 (PPI-1), phospholamban (PLB) and Ca(2+)-ATPase (SERCA-2), ryanodine receptor (RyR) were detected by western blot or RT-PCR. The activity of SERCA-2 was measured using Ca(2+)-ATPase kit. Diabetic rats showed impaired cardiac structure and function compared with control rats. The expression of PKC, PLB increased significantly, while the PPI-1, SERCA-2 and RyR expression decreased. Treatment with breviscapine could reverse the cardiac dysfunction and structure changes in diabetic cardiomyopathy rats, and decrease the expression of PKC and PLB, as well as increase the expression of PPI-1, SERCA-2 and RyR. The protective effect of breviscapine was dose related. This study showed that breviscapine could regulate the expression of PKC, PPI-1, PLB and SERCA-2 and have protective effect on diabetic cardiomyopathy.

Breviscapine ameliorates hypertrophy of cardiomyocytes induced by high glucose in diabetic rats via the PKC signaling pathway.

AIM: To investigate the influence of breviscapine on high glucose-induced hypertrophy of cardiomyocytes and the relevant mechanism in vitro and in vivo. METHODS: Cultured neonatal cardiomyocytes were divided into i) control; ii) high glucose concentrations; iii) high glucose+PKC inhibitor Ro-31-8220; iv) high glucose+breviscapine; or v) high glucose+NF-kappaB inhibitor BAY11-7082. Cellular contraction frequency and volumes were measured; the expression of protein kinase C (PKC), NF-kappaB, TNF-alpha, and c-fos were assessed by Western blot or reverse transcription-polymerase chain reaction (RT-PCR). Diabetic rats were induced by a single intraperitoneal injection of streptozotocin, and randomly divided into i) control rats; ii) diabetic rats; or iii) diabetic rats administered with breviscapine (10 or 25 mg x kg(-1) x d(-1)). After treatment with breviscapine for six weeks, the echocardiographic parameters were measured. All rats were then sacrificed and heart tissue was obtained for microscopy. The expression patterns of PKC, NF-kappaB, TNF-alpha, and c-fos were measured by Western blot or RT-PCR. RESULTS: Cardiomyocytes cultured in a high concentration of glucose showed an increased pulsatile frequency and cellular volume, as well as a higher expression of PKC, NF-kappaB, TNF-alpha, and c-fos compared with the control group. Breviscapine could partly prevent these changes. Diabetic rats showed relative cardiac hypertrophy and a higher expression of PKC, NF-kappaB, TNF-alpha, and c-fos; treatment with breviscapine could ameliorate these changes in diabetic cardiomyopathy. CONCLUSION: Breviscapine prevented cardiac hypertrophy in diabetic rats by inhibiting the expression of PKC, which may have a protective effect in the pathogenesis of diabetic cardiomyopathy via the PKC/NF-kappaB/c-fos signal transduction pathway.

Senescent endothelial progenitor cells from dogs with pulmonary arterial hypertension: a before-after self-controlled study.

Previous studies have underlined the importance of endothelial dysfunction and microvascular occlusion in the pathogenesis of pulmonary artery hypertension (PAH). Since the endothelial progenitor cells (EPCs) are involved in maintaining endothelial homeostasis, we observed the change of peripheral EPCs in canines before and after PAH onset. PAH was induced by intra-pulmonary artery injection of dehydromonocrotaline (DHMC) in nine beagles. Before and 48 h and 6 weeks after DHMC injection, 40 ml peripheral blood was obtained from the femoral vein. Circulating EPCs were identified as CD133 + KDR + cells and numerated by fluorescence-activated cell sorter; the EPCs functional capacity was determined by in vitro tubule-forming assay. The senescence of EPCs was determined by beta-galactosidase staining. At each time point, 2 ml blood from femoral artery was obtained for arterial oxygen pressure (PaO(2)). Forty-eight hours after DHMC injection, treated beagles suffered from hypoxemia; however, both the number and the tubule-forming capacity of EPCs were transiently raised. Six weeks later, PAH was confirmed by obviously high mean pulmonary arterial pressure (20.2 +/- 1.64 vs. 11.3 +/- 2.0 mmHg, p < 0.05) and low PaO(2) (69.30 +/- 9.15 vs. 95.94 +/- 1.43 mmHg, p < 0.01) in beagles after DHMC treatment, and their EPCs exhibited a predominant decrease in either the number (206.1 +/- 26.8 vs. 632.8 +/- 42.8 cells/ml blood, p < 0.01) or the tubule-forming capacity (21.1 +/- 2.8 vs. 11.2 +/- 2.8 tubules/x200 field, p < 0.01). Additionally, senescence-associated beta-galactosidase-positive EPCs were significantly increased. Our data suggested that, after the acute stage of DHMC injury to pulmonary vessels, the EPCs from PAH beagles suffered from exhaustion and senescence.

[The effect of chelerythrine on the hypertrophy of cardiac myocytes of neonatal rats induced by different glucose levels and its mechanism].

The purpose of this study is to investigate the effect of chelerythrine on the hypertrophy of cardiomyocytes of neonatal rats induced by different glucose levels and its mechanism. Using cultured neonatal ventricular myocytes as a model, groups were divided as: control (5 mmol x L(-1)); high glucose level (10, 15, 20, and 25.5 mmol x L(-1)); high glucose level (25.5 mmol x L(-1)) add different concentrations of chelerythrine (1 and 8 micromol x L(-1)); and control glucose level (5 mmol x L(-1)) add different concentrations of chelerythrine (1 and 8 micromol x L(-1)). Different groups of cardiomyocytes after adding corresponding treat factors were cultured for 48 hours. Cardiomyocytes' diameters and protein level were measured and the expression of PKC-alpha, PKC-beta2, p-PKC-alpha, and p-PKC-beta2 were measured by Western blotting. Compared with control group, neonatal myocytes cultured in high glucose levels showed increased cellular volumes, protein level and expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2. When chelerythrine was added, cellular volumes, protein level and expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2 were significantly reduced. But in 1 micromol x L(-1) chelerythrine group, the expression of PKC-beta2 was not significantly reduced. The result suggested that chelerythrine can reverse the hypertrophy induced by different glucose levels on the cardiac myocytes, it may have protective effect against diabetic cardiomyopathy via PKC passageway.

Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: open-label pilot study.

Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, our previous studies suggested that autologous EPC transplantation was feasible, safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in adults with IPAH. Thus, we hypothesized that transplantation of EPCs would improve exercise capacity and pulmonary hemodynamics in children with IPAH. Thirteen children with IPAH received intravenous infusion of autologous EPCs. The right-sided heart catheterization and 6-MWD test were performed at baseline and at the time of 12 wk after cell infusion. At the time of 12 wk, mPAP decreased by 6.4 mmHg from 70.3 +/- 19.0 to 63.9 +/- 19.3 mmHg (p = 0.015). PVR decreased by approximately 19% from 1118 +/- 537 to 906 +/- 377 dyn s/cm(5) (p = 0.047). CO increased from 3.39 +/- 0.79 to 3.85 +/- 0.42 L/min (p = 0.048). The 6-MWD increased by 39 m from 359 +/- 82 to 399 +/- 74 m (p = 0.012). NYHA functional class also improved. There were no severe adverse events with cell infusion. The small pilot study suggested that intravenous infusion of autologous EPCs was feasible, safe, and associated with significant improvements in exercise capacity, NYHA functional class, and pulmonary hemodynamics in children with IPAH. Confirmation of these results in a randomized controlled trial are essential.

Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: a pilot randomized controlled trial.

OBJECTIVES: The goal of this study was to investigate the feasibility, safety, and initial clinical outcome of intravenous infusion of autologous endothelial progenitor cells (EPCs) in patients with idiopathic pulmonary arterial hypertension (IPAH). BACKGROUND: Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, clinical studies suggest that autologous progenitor cell transplantation is feasible and safe in patients with ischemic diseases. METHODS: We conducted a prospective, randomized trial comparing the effects of EPC transplantation plus conventional therapy with those of conventional therapy alone in patients with IPAH. The primary end point was change in the 6-min walk distance using a standardized protocol. The secondary end points were changes in hemodynamic variables as assessed by right heart catheterization. RESULTS: After 12 weeks of follow-up, the mean distance walked in 6 min increased by 48.2 m in the cell infusion group (from 263 +/- 42 m to 312 +/- 34 m), and an increase of 5.7 m occurred in the conventional therapy group (from 264 +/- 42 m to 270 +/- 44 m). The mean difference between the 2 groups was 42.5 m (95% confidence interval 28.7 to 56.3 m, p < 0.001). The patients in the cell infusion group also had significant improvement in mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac output. There were no severe adverse events with cell infusion. CONCLUSIONS: This preliminary study showed that intravenous infusion of autologous EPCs seemed to be feasible and safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in patients with IPAH. (Safety and Efficacy Study of Transplantation of EPCs to Treat Idiopathic Pulmonary Arterial Hypertension; http://www.clinicaltrials.gov/ct/show/NCT00257413?order=1; NCT00257413).

[Changes of endothelial progenitor cells from peripheral blood in patients with coronary heart diseases].

OBJECTIVE: To investigate alterations of endothelial progenitor cells (EPCs) from peripheral blood in patients with coronary heart diseases. METHODS: Twenty patients with coronary heart diseases (CHD) and 20 matched control subjects were included in the study. Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. After cultured for 7 days, attached cells were cytochemically analyzed. EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin-binding by laser scanning confocal microscope with direct fluorescent staining. EPCs proliferation and migration were measured by MTT assay and modified Boyden chamber assay, respectively. EPCs adhesion assay was performed by replating on fibronectin-coated dishes, then adherent cells were counted. RESULTS: The number of EPCs was significantly reduced in patients with CHD compared with that of age-matched control subjects (31.8+/-7.7 compared with 59.5 +/-10.6 EPCs/x 200 field; P<0.05). In addition, the functional activity of EPCs such as proliferation, migration and adhesive capacity was also impaired in patients with CHD. CONCLUSION: EPCs number and functional activity are significantly decreased in patients with CHD.

[Effects of Ginkgo biloba extract on number and activity of endothelial progenitor cells from peripheral blood].

AIM: To investigate whether Ginkgo biloba extract can augment endothelial progenitor cell (EPC) number, and promote EPC proliferation, migration and adhesion. METHODS: Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. After 7 days of culture, attached cells were stimulated with Ginkgo biloba extract (10, 25 and 50 mg x L(-1)) or vehicle control for the respective time points (6, 12, 24 and 48 h). EPC were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. EPC were further documented by demonstrating the expression of CD34, VEGFR-2 and AC133 with flow cytometry. EPC proliferation, migration and in vitro vasculogenesis activity were assayed with MTT assay, modified Boyden chamber assay and in vitro vasculogenesis kit, respectively. EPCs adhesion assay was performed by replating MNCs on fibronectin-coated dishes, and then counting adherent cells. RESULTS: Incubation of isolated human MNCs with Ginkgo biloba extract increased the number of EPC, maximum at 25 mg x L(-1), 24 hours (approximately 1-fold increase, P < 0.01). In addition, Ginkgo biloba extract promotes EPC proliferative, migratory, adhesive and in vitro vasculogenesis capacity. CONCLUSION: Ginkgo biloba may promote EPC augmentation and enhance its functional activity.

[Effects of puerarin on number and activity of endothelial progenitor cells from peripheral blood].

OBJECTIVE: To investigate whether puerarin can augment endothelial progenitor cells (EPCs) numbers, promote EPC proliferation, migration and adhesion. METHOD: Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. After 7 days culture, attached cells were stimulated with puerarin (to make a series of final concentrations: 0. 1, 0.5, 1, 3 mmol x L(-1)) or vehicle control for the respective time points (6, 12, 24, 48 h). EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. EPCs proliferation, migration and in vitro vasculogenesis activity were assayed with MT assay, modified Boyden chamber assay and in vitro vasculogenesis kit, respectively. EPCs adhesion assay was performed by replating those on fibronectin-coated dishes, then adherent cells were counted. RESULT: Incubation of isolated human MNCs with puerarin dose increased the number of EPCs, maximum at 3 mmol x L(-1), 24 hours (approximately 1-fold increase, P < 0.01). In addition, puerarin also promoted EPC proliferative, migratory, adhesive and in vitro vasculogenesis capacity. CONCLUSION: Puerarin can augment the number of EPCs with enhanced functional activity.

Effects of puerarin on number and activity of endothelial progenitor cells from peripheral blood.

AIM: To investigate whether puerarin can augment endothelial progenitor cells (EPCs) numbers, promote EPC proliferative, migratory, adhesive, and in vitro vasculogenesis capacity. METHODS: EPCs were characterized as adherent cells by double staining of DiLDL-uptake and lectin binding under a laser scanning confocal microscope. Expression of KDR, VEGFR-2, and AC133 was detected by flow cytometry. EPCs proliferation, migration and in vitro vasculogenesis were determined with MTT assay, modified Boyden chamber assay, and in vitro vasculogenesis kit, respectively. EPCs adhesive assay was performed by replating those on fibronectin-coated dishes, then adherent cells were counted. RESULTS: Incubation of isolated human MNCs with puerarin 0.1-3 mmol/L increased the number of EPCs, EPC proliferative, migratory, adhesive, and in vitro vasculogenesis capacity in a concentration- and time-dependent manner, which reached maximum at 3 mmol/L, 24 h (approximately 1-fold increase, P<0.01). CONCLUSION: Puerarin enhanced EPCs functional activity.

Statins contribute to enhancement of the number and the function of endothelial progenitor cells from peripheral blood.

The aim of the present study was to investigate whether fluvastatin augments the number of endothelial progenitor cells (EPCs), and promotes EPCs proliferation, migration and adhesion. Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation. The cells were then plated on fibronectin-coated culture dishes. After being cultured for 7 d, the attached cells were stimulated with fluvastatin (final concentrations: 0.01, 0.1, 1, 10 micromol/L), simvastatin (1 micromol/L) or a vehicle for the respective time points (6, 12, 24 and 48 h). EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. EPCs were further documented by demonstrating the expression of KDR, VEGFR-2 and AC133 with flow cytometry. EPCs proliferation, migration and in vitro vasculogenesis activity were assayed by MTT assay, modified Boyden chamber assay and in vitro vasculogenesis kit, respectively. EPCs adhesion assay was performed by replating it on fibronectin-coated dishes, and the adherent cells were then counted. In addition, we also studied EPCs culture assay of peripheral blood from fluvastatin-treated animals in vivo. Incubation of isolated human MNCs with fluvastatin dose- and time-dependently increased the number of EPCs, while reached the maximum 24 h after the administration at 1 micromol/L, (2.5-fold increase, P<0.05). Moreover, treatment of rats with fluvastatins elevated the number of EPCs (3-fold increase, P<0.05), thus extending the in vitro data. In addition, fluvastatin also promoted EPC proliferation, migration, adhesion and in vitro vasculogenesis in a concentration-dependent manner. The effects of fluvastatin on EPCs were compared with those of simvastatin at the same concentration (1 micromol/L), with a result of no statistical difference. The results of the present study define a novel mechanism of the action of statins: the augmentation of EPCs with enhanced functional activity.

[Effects of hypercholesterolemia on the number and activity of endothelial progenitor cells in peripheral blood].

OBJECTIVE: To investigate whether hypercholesterolemia has influences on the number and activity of endothelial progenitor cells (EPCs). METHODS: Mononuclear cells were isolated from patients with hypercholesterolemia (n = 20) and age-matched control subjects (n = 20). EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. EPCs proliferation and migration were assayed by MTT assay and modified Boyden chamber assay, respectively. EPCs adhesion assay was performed by replating cells on fibronectin-coated dishes, then counting the adherent cells. RESULTS: The number of EPCs was significantly reduced in patients with hypercholesterolemia as compared with that in control subjects [(41.8 +/- 8.7 vs 64.5 +/- 16.6) EPCs/x 200 fields; P < 0.05] and it was inversely correlated with total cholesterol levels (r = -0.659, P < 0.001) and LDL cholesterol levels (r = -0.611, P < 0.001). In addition, EPCs proliferative, migratory and adhesive capacity were also impaired. CONCLUSION: It is suggested that a novel pathophysiological mechanism of hypercholesterolemia may be defined i.e. reduction of EPCs with decreased functional activity.