Prevalence and correlates of mitral regurgitation in the current era: an echocardiography study of a Chinese patient population.

OBJECTIVE: Little is known about the prevalence of mitral regurgitation (MR) in China until now. The objective of the study was to survey the prevalence, correlates and causes of MR in a large Chinese patient population in the current era. METHODS: This study retrospectively analysed the echocardiographic database of the subjects visiting our heart centre from 2010 to 2012. RESULTS: A total of 134,874 cases were included into the analysis. Of these cases 42.44%, 1.63%, 1.44% had mild MR(+), moderate MR(2+) and severe MR(3+/4+), respectively. The rate of MR increased with age. The rate of severe MR was 22.14% in subjects with a left ventricular ejection fraction (LVEF) < 30%, 13.0% in subjects with a LVEF of 30-44%, 15.74% in subjects with left ventricular end-systolic diameter (LVSD) of 50-59 mm, and 27.28% in those with LVSD ≥ 60 mm. The aetiology of 1,948 cases of severe MR was as follows: 972 (49.9%) patients had primary causes, of whom 55 had rheumatic heart disease, 96 had infectious endocarditis, 141 had papillary muscle dysfunction and 608 had degenerative disease, and the other 976 patients had secondary MR. CONCLUSION: MR is common in subjects referring to our heart centre in China. Severe MR is frequent in patients with decreased LVEF or an enlarged left ventricle or atrium. Degenerative disease and secondary changes are the most common causes for severe MR.

Early and long-term effect of thoracic endovascular aortic repair for Stanford B aortic dissection.

BACKGROUND: Uncomplicated Stanford B acute aortic dissection (AAD) is generally treated with medical management; whereas complicated dissections require surgery or thoracic endovascular aortic repair (TEVAR). Studies have demonstrated that long-term outcomes with medical management are suboptimal. Therefore, we sought to investigate the early and long-term clinical efficacy of TEVAR for Stanford B AAD. MATERIALS AND METHODS: From March 2004 to January 2008, 63 consecutive patients were treated and retrospectively placed into either one of the two groups, the TEVAR group (n = 42) and the medicine group (n = 21). All TEVAR procedures were performed in the acute phase. The changes of true and false lumen diameter were monitored with computed tomography angiography examinations in the thoracic aorta at the level of the stented segment at long-term follow-up. RESULTS: As compared with the medicine group, the age at intervention in the TEVAR group was higher (p < 0.05), and they also had more patent false lumen in this group. Patients in the TEVAR group had significantly longer hospital stays than those in the medicine group (p < 0.01). The incidence of the early events was not significantly different between the two groups. The incidence of aortic-related late events and late death were significantly higher in the medicine group than those in the TEVAR group. Log-rank tests demonstrated that patients treated with medical management had significantly more late adverse events than did those treated with TEVAR (p < 0.01). At 1-year follow-up, the true lumen diameter in the thoracic aorta at the level of the stented segment increased significantly after TEVAR, and the mean reduction of false lumen diameter was highly significant. The remodeling was stable at 3 and 5 years after TEVAR. CONCLUSION: Patients with Stanford B AAD treated with TEVAR experienced fewer late adverse events than those treated with medical management, TEVAR could be an effective treatment for Stanford B AAD.

Potential of 5-azacytidine induction decidual stromal cells from maternal human term placenta towards cardiomyocyte-like cells in serum-free medium.

Decidual stromal cells (DSCs) from maternal term placenta represent a potential source of cells for the treatment of cardiovascular and graft-versus-host diseases. However, it is not clear whether DSCs could be induced towards cardiomyocyte-like differentiation. We chose the placentas which should bred male new-baby. We isolated DSCs from placenta by tissue adherence. The morphology, immunophenotype, and multi-lineage potential were analyzed. Karyotype analysis (G-band) was performed to determine the source and karyotype stability of DSCs. DSCs were induced by 5-azacytidine. Expression of Myf5, α-cardiac actin, Cardiac troponin T (cTnT) and GAPDH was assessed by PCR, and cTnT expression was also analyzed by immunofluorescence. Karyotype analyses indicated that cells were derived from the maternal matrix. After induction with 5-azacytidine, DSCs expressed the cardiac-specific markers Myf5, myogenin and cTnT, indicating differentiation towards cardiomyocyte-like cells.

Risk factors of early and late mortality after thoracic endovascular aortic repair for complicated stanford B acute aortic dissection.

BACKGROUND AND AIM OF THE STUDY: The risk factors associated with death in complicated Stanford B acute aortic dissection (AAD) after thoracic endovascular aortic repair (TEVAR) are poorly understood. The aim of this study was to evaluate the early and late events and mortality of complicated Stanford B AAD associated with TEVAR. METHODS: Sixty-two patients with complicated Stanford B AAD undergoing TEVAR were included in this study. RESULTS: Primary technical success of TEVAR was achieved in 61 (98.39%) cases. The early mortality rate was 9.68%. Procedural type I endoleak (p = 0.007, OR = 7.71, 95% CI: 1.75-34.01) and cardiac tamponade (p = 0.010, OR = 8.86, 95% CI: 1.70-4 6.14) were the significant predictors of early death in the multivariate model. The late mortality was 16.07%. Cox regression analysis revealed rupture of false lumen (p = 0.001, hazard ratio = 21.96, 95% CI: 3.02-82.12), postoperative myocardial infarction (p = 0.001, hazard ratio = 9.86, 95% CI: 2.12-39.64), and acute renal failure (p = 0.024, hazard ratio = 3.98, 95% CI: 1.26-12.11) to be independent risk factors of late mortality. CONCLUSIONS: Type I procedural endoleak and cardiac tamponade were the significant predictors of early death in patients of complicated Stanford B AAD undergoing TEVAR. Rupture of false lumen, postoperative myocardial infarction, and acute renal failure were the independent risk factors for late death after TEVAR.

Monitoring the biology stability of human umbilical cord-derived mesenchymal stem cells during long-term culture in serum-free medium.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that have an immunosuppressive effect. The biological stability of MSCs in serum-free medium during long-term culture in vitro has not been elucidated clearly. The morphology, immunophenotype and multi-lineage potential were analyzed at passages 3, 5, 10, 15, 20, and 25 (P3, P5, P10, P15, P20, and P25, respectively). The cell cycle distribution, apoptosis, and karyotype of human umbilical cord-derived (hUC)-MSCs were analyzed at P3, P5, P10, P15, P20, and P25. From P3 to P25, the three defining biological properties of hUC-MSCs [adherence to plastic, specific surface antigen expression, multipotent differentiation potential] met the standards proposed by the International Society for Cellular Therapy for definition of MSCs. The cell cycle distribution analysis at the P25 showed that the percentage of cells at G0/G1 was increased, compared with the cells at P3 (P < 0.05). Cells at P25 displayed an increase in the apoptosis rate (to 183 %), compared to those at P3 (P < 0.01). Within subculture generations 3-20 (P3-P20), the differences between the cell apoptotic rates were not statistically significant (P > 0.05). There were no detectable chromosome eliminations, displacements, or chromosomal imbalances, as assessed by the karyotyping guidelines of the International System for Human Cytogenetic Nomenclature (ISCN, 2009). Long-term culture affects the biological stability of MSCs in serum-free MesenCult-XF medium. MSCs can be expanded up to the 25th passage without chromosomal changes by G-band. The best biological activity period and stability appeared between the third to 20th generations.

Cystatin C, N-terminal probrain natriuretic peptides and outcomes in acute heart failure with acute kidney injury in a 12-month follow-up: Insights into the cardiorenal syndrome.

BACKGROUND: Cystatin C (Cys C) has been implicated as a prognostic marker in cardiovascular disease. The aim of this study was to evaluate the value of Cys C as a marker of acute kidney injury (AKI) in acute heart failure (AHF), the impact of Cys C and N-terminal probrain natriuretic peptides (NT-proBNP) on in-hospital and 12 months mortality were also investigated. MATERIALS AND METHODS: A total of 162 patients with AHF were enrolled. NT-proBNP, Cys C, serum creatinine (Scr), blood urea nitrogen (BUN) and parameters of echocardiography were measured for analyze. The in-hospital and 12 months mortality was analyzed. RESULTS: There was 28 (17%) of all AHF patients with AKI. Compared with no-AKI patients, the levels of Cys C (1.51 ± 0.34 vs. 1.32 ± 0.29, P = 0.003) and NT-proBNP (8163.87 ± 898.06 vs. 5922.45 ± 576.73, P = 0.001) were higher in AKI patients. Higher levels of NT-proBNP (odds ratio (OR) = 1.92, 95% confidence interval (CI): 2.19-10.98, P = 0.018, OR = 4.31, 95% CI: 2.35-9.82, P = 0.002, respectively) and Cys C (OR = 1.48, 95% CI: 1.75-4.16, P = 0.027, OR = 2.72, 95% CI: 1.92-4.28, P = 0.017, respectively) were independent association with the in-hospital and 12 months mortality. Cys C was positively correlated with NT-proBNP (r = 0.87, P < 0.001). Combining tertiles of Cys C and NT-proBNP improved risk stratification further. Compared with patients without AKIcysC, patients with AKIcysC was associated with higher in-hospital (7/28 vs. 10/134, P = 0.002) and 12-month mortality (13/28 vs. 32/134, P = 0.001). CONCLUSION: Cys C was not only a promising risk marker in patients hospitalized for AHF, but also an independent predictor of 12-month mortality. Combining tertiles of Cys C and NT-proBNP could be used to distinguish the mortality risk identification of patients with AHF. AKI was an independent predictor of in-hospital and 12-month mortality.

Intrinsic effects of gold nanoparticles on proliferation and invasion activity in SGC-7901 cells.

Although biomedical applications of functionalized nanoparticles have taken significant strides, biological characterization of unmodified nanoparticles remains unclear. In the present study, we investigated the cell viability and invasion activity of gastric cancer cells after treatment with gold nanoparticles. The growth of SGC-7901 cells was inhibited significantly after treatment with 5-nm gold nanoparticles, and the cell invasion decreased markedly. These effects were not seen by different size gold nanoparticles (10, 20 and 40 nm). The attenuated invasion activity may be associated with the decreased expression of matrix metalloproteinase 9 and intercellular adhesion molecule-1. These data indicated that the response of SGC-7901 cells to gold nanoparticles was strongly associated with their unique size-dependent physiochemical properties. Therefore, we provided new evidence for the effect of gold nanoparticles on gastric cancer cell proliferation and invasion in vitro, making a contribution to the application of gold nanoparticles to novel therapies in gastric cancer.

Overexpressing NKx2.5 increases the differentiation of human umbilical cord drived mesenchymal stem cells into cardiomyocyte-like cells.

BACKGROUND: Nkx2.5 is one of the transcription factors in early myocardial cell development and Nkx2.5 gene expression increased gradually in the course of stem cells differentiation. In this study, this study aimed to investigate whether overexpression of NKx2.5 increases human umbilical cord drived mesenchymal stem cells (hUCMSCs) transdifferentiation into a cardiac phenotype in vitro. METHODS: hUCMSCs were transduced with Nkx2.5 at the third passage (transduced group). Gene expression of cTnI, Desmin, Nkx2.5 and GATA-4 in transduced group was analyzed using real-time PCR and immunohistochemistry, and compared with no-transduced hUCMSCs (control group), which were transfected with green fluorescent protein (GFP) only. RESULTS: Compared with control group, hUCMSCs in transduced group were shown by immunofluorescence to have higher expression of Nkx2.5. After incubation for 4 weeks, the mRNA and protein expression of cardiac genes, including cTnI, Desmin, Nkx2.5 and GATA-4, were up- regulated in transduced group compared with control group (P<0.05). CONCLUSIONS: Overexpression of Nkx2.5 significantly promotes the differentiation of hUCMSCs into cardiomyocytes and increases the expression of cTnI, Desmin, Nkx2.5, and GATA-4.

Inhibitor of p53-p21 pathway induces the differentiation of human umbilical cord derived mesenchymal stem cells into cardiomyogenic cells.

P53 is shown recently to play an important role in the proliferation and differentiation of mesenchymal stem cells. In this study, human umbilical cord derived mesenchymal stem cells (hUCMSCs) were isolated and purified from the umbilical cords of normal or cesarean term deliveries, after treatment with 20 µmol/L PFT-α for 24 h, hUCMSCs were continued to be cultured for 4 weeks, cardiac-specific protein expression of cTnI, Desmin and Nkx2.5 was determined using immunofluorescence assay and RT-PCR. The expression of p53 and p21 was detected by western blot. Results showed that no expression of cTnI, Desmin or Nkx2.5 was observed in the control and the PFT-α group at 1 week after induction. However, after 4 weeks, while control group still had little expression of cTnI, Desmin and Nkx2.5, the PFT-α group demonstrated strong expression of cTnI, Desmin and Nkx2.5 (P < 0.001). At 4 weeks after induction, differentiation rate of cardiomyogenic cells in the PFT-α group (36.98 %) was significantly higher than that in the control group (4.41 %) (P < 0.01). Western blot analysis show that downregulation of p53 and p21 was seen in the PFT-α group at 4 weeks. The difference compared with the control group was statistically significant (P < 0.01). In conclusion, PFT-α can promote the differentiation of hUCMSCs into cardiomyogenic cells by modulating the p53-p21 pathway.

Comparison of the Effects of Different Cryoprotectants on Stem Cells from Umbilical Cord Blood.

Purpose. Cryoprotectants (CPA) for stem cells from umbilical cord blood (UCB) have been widely developed based on empirical evidence, but there is no consensus on a standard protocol of preservation of the UCB cells. Methods. In this study, UCB from 115 donors was collected. Each unit of UCB was divided into four equal parts and frozen in different kinds of cryoprotectant as follows: group A, 10% ethylene glycol and 2.0% dimethyl sulfoxide (DMSO) (v/v); group B, 10% DMSO and 2.0% dextran-40; group C, 2.5% DMSO (v/v) + 30 mmol/L trehalose; and group D, without CPA. Results. CD34(+), cell viability, colony forming units (CFUs), and cell apoptosis of pre- and postcryopreservation using three cryoprotectants were analyzed. After thawing, significant differences in CD34(+) count, CFUs, cell apoptosis, and cell viability were observed among the four groups (P < 0.05). Conclusion. The low concentration of DMSO with the addition of trehalose might improve the cryopreservation outcome.

Mesenchymal Stem Cells and Mononuclear Cells From Cord Blood: Cotransplantation Provides a Better Effect in Treating Myocardial Infarction.

The aim of this study was to evaluate the effect of cotransplanting mononuclear cells from cord blood (CB-MNCs) and mesenchymal stem cells (MSCs) as treatment for myocardial infarction (MI). Transplanting CD34+ cells or MSCs separately has been shown effective in treating MI, but the effect of cotransplanting CB-MNCs and MSCs is not clear. In this study, MSCs were separated by their adherence to the tissue culture. The morphology, immunophenotype, and multilineage potential of MSCs were analyzed. CB-MNCs were separated in lymphocyte separation medium 1.077. CD34+ cell count and viability were analyzed by flow cytometry. Infarcted male Sprague-Dawley rats in a specific-pathogen-free grade were divided into four treatment groups randomly: group I, saline; group II, CB-MNCs; group III, MSCs; and group IV, CB-MNCs plus MSCs. The saline, and CB-MNCs and/or MSCs were injected intramyocardially in infarcted rats. Their cardiac function was evaluated by echocardiography. The myocardial capillary density was analyzed by immunohistochemistry. Both cell types induced an improvement in the left ventricular cardiac function and increased tissue cell proliferation in myocardial tissue and neoangiogenesis. However, CB-MNCs plus MSCs were more effective in reducing the infarct size and preventing ventricular remodeling. Scar tissue was reduced significantly in the CB-MNCs plus MSCs group. MSCs facilitate engraftment of CD34+ cells and immunomodulation after allogeneic CD34+ cell transplantation. Cotransplanting MSCs and CB-MNCs might be more effective than transplanting MSCs or CB-MNCs separately for treating MI. This study contributes knowledge toward effective treatment strategies for MI.

Expression and significance of DLL4--Notch signaling pathway in the differentiation of human umbilical cord derived mesenchymal stem cells into cardiomyocytes induced by 5-azacytidine.

hUCMSCs were isolated and purified from the umbilical cords of normal or cesarean term deliveries under sterile conditions. Flow cytometry analysis revealed that CD13, CD29, CD44, CD90, and CD105 were highly expressed on the surface of passage-3 hUCMSCs, but negative for CD31, CD34, CD45, and HLA-DR. Immunocytochemistry showed that 5-azacytidine (5-aza) could induce the cTnI expression of hUCMSCs. RT-PCR showed that a stable higher level expression of DLL4 and Notch1 gene in 5-aza-induced group was observed compared to that in the control group. There was a higher expression level in the induced group. Compared with control group, the expression levels of Notch1 were, respectively, increased 6.60, 7.36, 7.595, and 7.805 times at 1, 3, 5, and 7 days after intervention of 5-aza. Statistically higher Ct value of Notch1 mRNA in induced group was observed in comparison with that of the control group (0.51 ± 0.21 vs 7.85 ± 0.35, t = 35.98, P < 0.01). The expression level of DLL4 increased stably compared with the control group. Compared with control group, the expression levels of DLL4 were, respectively, increased 11.53, 10.1, 10.17, and 11.46 times at 1, 3, 5, and 7 days after intervention of 5-aza. There was a significant difference of DLL4 Ct value between the 5-aza-induced group and the control group (1.60 ± 0.49 vs 12.42 ± 0.73, t = 11.71, P < 0.01). In conclusion, hUCMSCs can be differentiated into myocardial cells in vitro. The DLL4-Notch signaling pathway may be involved in the differentiation of hUCMSCs into cardiomyocytes induced by 5-aza.

Comparison of biological characteristics of mesenchymal stem cells derived from maternal-origin placenta and Wharton's jelly.

INTRODUCTION: Although mesenchymal stem cells (MSCs) from different sources share many similar characteristics, they also exhibit individual properties. In this study, we compared MSCs derived from Wharton's jelly in the umbilical cord with those derived from the decidual basalis in the maternal part of the placenta to better understand the similarities and differences between these two cell types. METHOD: The morphology, immunophenotype (as assessed using flow cytometry), and multi-lineage differentiation potential were analyzed. Karyotype analysis was carried out to determine the origin of the MSCs. Growth kinetics were evaluated using analysis of the population doubling time and cell cycle. Immunosuppressive function was analyzed using mixed lymphocyte culture. RESULTS: MSCs from Wharton's jelly and the decidua basalis exhibited similar morphology, immunophenotype, and differentiation potential to osteogenesis and adipogenesis. The percentage of MSCs in the G0/G1 phase was higher in the case of Wharton's jelly than in the case of the decidua basalis (P < 0.05). Decidual MSCs displayed more remarkable immunosuppressive effects on phytohemagglutinin-stimulated T-cell proliferation (P < 0.05). CONCLUSION: MSCs from both sources had similar basic biological properties, but decidual MSCs had slower proliferation and stronger immunosuppressive function.

Changes of monocyte subsets in patients with acute coronary syndrome and correlation with myocardial injury markers.

OBJECTIVE: To explore the changes of peripheral blood monocytes subsets in acute coronary syndrome (ACS) and its clinical significance. METHODS: A total of 68 ACS patients and 27 healthy subjects (HS) were enrolled. Monocyte subset analysis was performed using flow cytometry: CD14++CD16-(Mon1), CD14++CD16+ (Mon2), and CD14+CD16++ (Mon3). RESULTS: 1. The number of Mon1 and Mon3 were significantly increased in ACS patients compared with HS (P<0.05) and Mon2 decreased in ACS patients (P<0.05). 2. The number of Mon1, Mon2, Mon3 was positively correlated with WBC count (P<0.05). The Mon2% was negatively correlated with the serum levels of LDH, CK, CK-MB (P<0.05). The number of Mon1, Mon3 was positively correlated with the serum levels of LDH, CK, CK-MB (P<0.05). CONCLUSION: The changes in different subsets of monocytes may be associated with pathogenesis of ACS and myocardial injury. The findings might be useful in the assessment of myocardial injury.

Karyotype stability of human umbilical cord-derived mesenchymal stem cells during in vitro culture.

The aim of this study was to investigate whether the chromosomes of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) change following in vitro culture for several generations. In the present study, umbilical cords from two healthy infants following cesarean delivery were collected aseptically and hUCMSCs were isolated by digestion with collagenase and trypsin, and then cultured in vitro. hUCMSCs with fibroblastic morphology were presented from the human umbilical cord tissue after 7 days of adherent culture. When cultured for 6 passages in vitro, the hUCMSCs maintained a stable spindle-shaped morphology. Cells reached the logarithmic growth phase after 3-4 days of culture. In addition, CD13, CD29, CD44, CD90 and CD105 were highly expressed in generations P3-P6. The expression of CD31, CD34, CD45 and HLA-DR was negative. Furthermore, karyotype analysis revealed a normal diploid karyotype with 46 chromosomes and no abnormal changes were found in chromosome structure. These findings suggest that when cultured for 6 passages in vitro, hUCMSCs maintain a stable immunophenotype and chromosome structure, which provides an experimental basis for the safety of hUCMSC cytotherapy.

RETRACTED: Effect of phentolamine on myocardial extracellular matrix of cardiac remodeling in rats.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the journal Editorial Office. The authors have plagiarized part of a paper that had already appeared in Chinese Journal of Arteriosclerosis 2014, 4, 362­366. article id: 1007­3949 (2014) 22-04-0362-05. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents an abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Human umbilical cord-derived mesenchymal stem cells do not undergo malignant transformation during long-term culturing in serum-free medium.

BACKGROUND: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are in the foreground as a preferable application for treating diseases. However, the safety of hUC-MSCs after long-term culturing in vitro in serum-free medium remains unclear. METHODS: hUC-MSCs were separated by adherent tissue culture. hUC-MSCs were cultured in serum-free MesenCult-XF medium and FBS-bases DMEM complete medium. At the 1st, 3rd, 5th, 8th, 10th, and 15th passage, the differentiation of MSCs into osteogenic, chondrogenic, and adipogenic cells was detected, and MTT, surface antigens were measured. Tumorigenicity was analyzed at the 15th passage. Conventional karyotyping was performed at passage 0, 8, and 15. The telomerase activity of hUC-MSCs at passage 1-15 was analyzed. RESULTS: Flow cytometry analysis showed that very high expression was detected for CD105, CD73, and CD90 and very low expression for CD45, CD34, CD14, CD79a, and HLA-DR. MSCs could differentiate into osteocytes, chondrocytes, and adipocytes in vitro. There was no obvious chromosome elimination, displacement, or chromosomal imbalance as determined from the guidelines of the International System for Human Cytogenetic Nomenclature. Telomerase activity was down-regulated significantly when the culture time was prolonged. Further, no tumors formed in rats injected with hUC-MSCs (P15) cultured in serum-free and in serum-containing conditions. CONCLUSION: Our data showed that hUC-MSCs met the International Society for Cellular Therapy standards for conditions of long-term in vitro culturing at P15. Since hUC-MSCs can be safely expanded in vitro and are not susceptible to malignant transformation in serum-free medium, these cells are suitable for cell therapy.

Resveratrol-induced augmentation of telomerase activity delays senescence of endothelial progenitor cells.

BACKGROUND: Previous studies have shown that resveratrol increases endothelial progenitor cell (EPC) numbers and functional activity. Increased EPC numbers and activity are associated with the inhibition of EPC senescence. In this study, we investigated the effect of resveratrol on the senescence of EPCs, leading to potentiation of cellular function. METHODS: EPCs were isolated from human peripheral blood and identified immunocytochemically. EPCs were incubated with resveratrol (1, 10, and 50 µmol/L) or control for specified times. After in vitro cultivation, acidic ß-galactosidase staining revealed the extent of senescence in the cells. To gain further insight into the underlying mechanism of the effect of resveratrol, we measured telomerase activity using a polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA) technique. Furthermore, we measured the expression of human telomerase reverse transcriptase (hTERT) and the phosphorylation of Akt by immunoblotting. RESULTS: Resveratrol dose-dependently inhibited the onset of EPC senescence in culture. Resveratrol also significantly increased telomerase activity. Interestingly, quantitative real-time PCR analysis demonstrated that resveratrol dose-dependently increased the expression of the catalytic subunit, hTERT, an effect that was significantly inhibited by pharmacological phosphatidylinositol 3-kinase (PI3-K) blockers (wortmannin). The expression of hTERT is regulated by the PI3-K/Akt pathway; therefore, we examined the effect of resveratrol on Akt activity in EPCs. Immunoblotting analysis revealed that resveratrol led to dose-dependent phosphorylation and activation of Akt in EPCs. CONCLUSION: Resveratrol delayed EPCs senescence in vitro, which may be dependent on telomerase activation.