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Circulating Progenitor Cells and Racial Differences.

ABSTRACT: RATIONALE:Blacks compared with whites have a greater risk of adverse cardiovascular outcomes. Impaired regenerative capacity, measured as lower levels of circulating progenitor cells (CPCs), is a novel determinant of adverse outcomes; however, little is known about racial differences in CPCs. OBJECTIVE:To investigate the number of CPCs, PC-mobilizing factors, PC mobilization during acute myocardial infarction and the predictive value of CPC counts in blacks compared with whites. METHODS AND RESULTS:CPCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34+, CD133+, VEGF2R+, and CXCR4+ epitopes in 1747 subjects, mean age 58.4±13, 55% male, and 26% self-reported black. Patients presenting with acute myocardial infarction (n=91) were analyzed separately. Models were adjusted for relevant clinical variables. SDF-1? (stromal cell-derived factor-1?), VEGF (vascular endothelial growth factor), and MMP-9 (matrix metallopeptidase-9) levels were measured (n=561), and 623 patients were followed for median of 2.2 years for survival analysis. Blacks were younger, more often female, with a higher burden of cardiovascular risk, and lower CPC counts. Blacks had fewer CD34+ cells (-17.6%; [95% confidence interval (CI), -23.5% to -11.3%]; P<0.001), CD34+/CD133+ cells (-15.5%; [95% CI, -22.4% to -8.1%]; P<0.001), CD34+/CXCR4+ cells (-17.3%; [95% CI, -23.9% to -10.2%]; P<0.001), and CD34+/VEGF2R+ cells (-27.9%; [95% CI, -46.9% to -2.0%]; P=0.04) compared with whites. The association between lower CPC counts and black race was not affected by risk factors or cardiovascular disease. Results were validated in a separate cohort of 411 patients. Blacks with acute myocardial infarction had significantly fewer CPCs compared with whites ( P=0.02). Blacks had significantly lower plasma MMP-9 levels ( P<0.001) which attenuated the association between low CD34+ and black race by 19% (95% CI, 13%-33%). However, VEGF and SDF-1? levels were not significantly different between the races. Lower CD34+ counts were similarly predictive of mortality in blacks (hazard ratio, 2.83; [95% CI, 1.12-7.20]; P=0.03) and whites (hazard ratio, 1.79; [95% CI, 1.09-2.94]; P=0.02) without significant interaction. CONCLUSIONS:Black subjects have lower levels of CPCs compared with whites which is partially dependent on lower circulating MMP-9 levels. Impaired regenerative capacity is predictive of adverse outcomes in blacks and may partly account for their increased risk of cardiovascular events.

SUBMITTER: Samman Tahhan A

PROVIDER: S-EPMC6202175 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Circulating Progenitor Cells and Racial Differences.

Samman Tahhan Ayman A Hammadah Muhammad M Kelli Heval Mohamed HM Kim Jeong Hwan JH Sandesara Pratik B PB Alkhoder Ayman A Kaseer Belal B Gafeer Mohamad Mazen MM Topel Matthew M Hayek Salim S SS O'Neal Wesley T WT Obideen Malik M Ko Yi-An YA Liu Chang C Hesaroieh Iraj I Mahar Ernestine E Vaccarino Viola V Waller Edmund K EK Quyyumi Arshed A AA

Circulation research 20180801 4

<h4>Rationale</h4>Blacks compared with whites have a greater risk of adverse cardiovascular outcomes. Impaired regenerative capacity, measured as lower levels of circulating progenitor cells (CPCs), is a novel determinant of adverse outcomes; however, little is known about racial differences in CPCs.<h4>Objective</h4>To investigate the number of CPCs, PC-mobilizing factors, PC mobilization during acute myocardial infarction and the predictive value of CPC counts in blacks compared with whites.<h ...[more]

PMID: 29930146

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Project description:BackgroundKidney transplantation (RTx) leads to amelioration of endothelial function in patients with advanced renal failure. Endothelial progenitor cells (EPCs) may play a key role in this repair process. The aim of this study was to determine the impact of RTx and immunosuppressive therapy on the number of circulating EPCs.MethodsWe analyzed 52 RTx patients (58±13 years; 33 males, mean ± SD) and 16 age- and gender-matched subjects with normal kidney function (57±17; 10 males). RTx patients received a calcineurin inhibitor (CNI)-based (65%) or a CNI-free therapy (35%) and steroids. EPC number was determined by double positive staining for CD133/VEGFR2 and CD34/VEGFR2 by flow cytometry. Stromal cell-derived factor 1 alpha (SDF-1) levels were assessed by ELISA. Experimentally, to dissociate the impact of RTx from the impact of immunosuppressants, we used the 5/6 nephrectomy model. The animals were treated with a CNI-based or a CNI-free therapy, and EPCs (Sca+cKit+) and CD26+ cells were determined by flow cytometry.ResultsCompared to controls, circulating number of CD34+/VEGFR2+ and CD133+/VEGFR2+ EPCs increased in RTx patients. There were no correlations between EPC levels and statin, erythropoietin or use of renin angiotensin system blockers in our study. Indeed, multivariate analysis showed that SDF-1--a cytokine responsible for EPC mobilization--is independently associated with the EPC number. 5/6 rats presented decreased EPC counts in comparison to control animals. Immunosuppressive therapy was able to restore normal EPC values in 5/6 rats. These effects on EPC number were associated with reduced number of CD26+ cells, which might be related to consequent accumulation of SDF-1.ConclusionsWe conclude that kidney transplantation and its associated use of immunosuppressive drugs increases the number of circulating EPCs via the manipulation of the CD26/SDF-1 axis. Increased EPC count may be associated to endothelial repair and function in these patients.

Project description:Background Ticagrelor use during acute coronary syndromes demonstrated a decrease in all-cause mortality in the PLATO (Platelet Inhibition and Patient Outcomes) trial. This effect has been attributed to a non-platelet-derived improvement in endothelial function. The aim of this study was to determine differences in the number of endothelial progenitor cells and/or circulating endothelial cells found in peripheral blood in patients treated with either ticagrelor or clopidogrel during non-ST-segment-elevation myocardial infarction. Methods and Results In this multicenter, randomized study ( NCT 02244710), patients were considered for inclusion after non-ST-segment-elevation myocardial infarction whenever they were P2Y12-inhibitor naïve. Ticagrelor and clopidogrel were allocated at a 1:1 ratio. Blood samples for determining endothelial progenitor cells and circulating endothelial cells were extracted before the antiplatelet loading dose, 48 hours after presentation of index symptoms, and 1 month after the event. A multichannel cytometer was used for optimal cell characterization. A total of 96 patients fulfilled the inclusion criteria. Circulating endothelial cell levels corrected by white blood cells were as follows at baseline, 48 hours, and 1 month: 44 (28-64), 50 (33-63), and 38 (23-62) cells/mL, respectively, for clopidogrel and 38 (29-60), 45 (32-85), and 35 (24-71) cells/mL, respectively, for ticagrelor ( P=0.6). Endothelial progenitor cell levels were 29 (15-47), 27 (15-33), and 18 (10-25) cells/mL, respectively, for clopidogrel and 20 (11-33), 22 (12-32), and 18 (11-29) cells/mL, respectively, for ticagrelor ( P=0.9). No differences in intraindividual changes were found. Conclusions Patients treated with ticagrelor during non-ST-segment-elevation myocardial infarction, in comparison to clopidogrel, showed similar levels of endothelial progenitor cells and circulating endothelial cells. These data suggest that the endothelial protective effect mediated by ticagrelor is not related to bone marrow physiology modulation. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02244710.

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Circulating Progenitor Cells and Racial Differences.

Publications

Circulating Progenitor Cells and Racial Differences.

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