Circulating Progenitor Cells in Patients With Coronary Artery Disease and Renal Insufficiency.
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ABSTRACT:
SUBMITTER: Mehta A
PROVIDER: S-EPMC7452291 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Circulating Progenitor Cells in Patients With Coronary Artery Disease and Renal Insufficiency.
Mehta Anurag A Tahhan Ayman S AS Liu Chang C Dhindsa Devinder S DS Nayak Aditi A Hooda Ananya A Moazzami Kasra K Islam Shabatun J SJ Rogers Steven C SC Almuwaqqat Zakaria Z Mokhtari Ali A Hesaroieh Iraj I Ko Yi-An YA Waller Edmund K EK Quyyumi Arshed A AA
JACC. Basic to translational science 20200812 8
Patients with coronary artery disease and renal insufficiency (RI) (estimated glomerular filtration rate <60 ml/min/1.73 m<sup>2</sup>) are at an increased risk of cardiovascular events. The contribution of regenerative capacity, measured as circulating progenitor cell (CPC) counts, to this increased risk is unclear. CPCs were enumerated as cluster of differentiation (CD) 45<sup>med+</sup> mononuclear cells expressing CD34+, CD133+, CXCR4+ (chemokine [C-X-C motif] receptor 4), and VEGF2R+ (vascu ...[more]
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Project description:BackgroundLow quantities of circulating progenitor cells (CPCs), specifically CD34+ populations, reflect impairment of intrinsic regenerative capacity. This study investigates the relationship between subsets of CPCs and adverse outcomes.Methods1366 individuals undergoing angiography for evaluation of coronary artery disease (CAD) were enrolled into the Emory Cardiovascular Biobank. Flow cytometry identified CPCs as CD45med blood mononuclear cells expressing the CD34 epitope, with further enumeration of hematopoietic CPCs as CD133+/CXCR4+ cells and endothelial CPCs as vascular endothelial growth factor receptor-2 (VEGFR2+) cells. Adjusted Cox or Fine and Gray's sub-distribution hazard regression models analyzed the relationship between CPCs and 1) all-cause death and 2) a composite of cardiovascular death and non-fatal myocardial infarction (MI).ResultsOver a median 3.1-year follow-up period (IQR 1.3-4.9), there were 221 (16.6%) all-cause deaths and 172 (12.9%) cardiovascular deaths/MIs. Hematopoietic CPCs were highly correlated, and the CD34+/CXCR4+ subset was the best independent predictor. Lower counts (≤median) of CD34+/CXCR4+ and CD34+/VEGFR2+ cells independently predicted all-cause mortality (HR 1.46 [95% CI 1.06-2.01], p = 0.02 and 1.59 [95% CI 1.15-2.18], p = 0.004) and cardiovascular death/MI (HR 1.50 [95% CI 1.04-2.17], p = 0.03 and 1.47 [95% CI 1.01-2.03], p = 0.04). A combination of low CD34+/CXCR4+ and CD34+/VEGFR2+ CPCs predicted all-cause death (HR 2.1, 95% CI 1.4-3.0; p = 0.0002) and cardiovascular death/MI (HR 2.0, 95% CI 1.3-3.2; p = 0.002) compared to those with both lineages above the cut-offs.ConclusionsLower levels of hematopoietic and endothelial CPCs indicate diminished endogenous regenerative capacity and independently correlate with greater mortality and cardiovascular risk in patients with CAD.
| S-EPMC9840693 | biostudies-literature
Project description:RationalePeripheral arterial disease (PAD) is a clinical manifestation of extracoronary atherosclerosis. Despite sharing the same risk factors, only 20% to 30% of patients with coronary artery disease (CAD) develop PAD. Decline in the number of bone marrow-derived circulating progenitor cells (PCs) is thought to contribute to the pathogenesis of atherosclerosis. Whether specific changes in PCs differentiate patients with both PAD and CAD from those with CAD alone is unknown.ObjectiveDetermine whether differences exist in PCs counts of CAD patients with and without known PAD.Methods and results1497 patients (mean age: 65 years; 62% men) with known CAD were identified in the Emory Cardiovascular Biobank. Presence of PAD (n=308) was determined by history, review of medical records, or imaging and was classified as carotid (53%), lower extremity (41%), upper extremity (3%), and aortic disease (33%). Circulating PCs were enumerated by flow cytometry. Patients with CAD and PAD had significantly lower PC counts compared with those with only CAD. In multivariable analysis, a 50% decrease in cluster of differentiation 34 (CD34+) or CD34+/vascular endothelial growth factor receptor-2 (VEGFR2+) counts was associated with a 31% (P=0.032) and 183% (P=0.002) increase in the odds of having PAD, respectively. CD34+ and CD34+/VEGFR2+ counts significantly improved risk prediction metrics for prevalent PAD. Low CD34+/VEGFR2+ counts were associated with a 1.40-fold (95% confidence interval, 1.03-1.91) and a 1.64-fold (95% confidence interval, 1.07-2.50) increases in the risk of mortality and PAD-related events, respectively.ConclusionsPAD is associated with low CD34+ and CD34+/VEGFR2+ PC counts. Whether low PC counts are useful in screening for PAD needs to be investigated.
| S-EPMC4975640 | biostudies-literature
Project description:Recently, we reported the properties of CD31-expressing cells in healthy individuals. However, the characteristics of CD31-expressing cells derived from coronary artery disease (CAD) patients remain unknown. This study aimed to investigate the relationship between circulating CD31(+) cells and CAD as well as their biological characteristics. Analysis with flow cytometry revealed that CD31(+) cells (C-CD31) from the peripheral blood (PB) of CAD patients exhibited low levels of T-cell marker and high levels of macrophage marker compared with the PB-CD31(+) cells from healthy individuals (H-CD31). In addition, the expression levels of multiple pro-angiogenic and chemokine genes were significantly down-regulated in C-CD31. However, inflammatory gene IL-1? was highly up-regulated in C-CD31. Patients with unstable angina (UA) had significantly more CD31(+) cells in the PB than healthy control group (P < 0.001). Moreover, there were significant correlations between the number of CD31(+) cells and cardiovascular (CV) disease activity (R = 0.318, P = 0.006) and the number of diseased coronaries (R = 0.312, P = 0.005). For the diagnostic category of UA, the area under curve was 0.803 (P < 0.001). In conclusion, C-CD31 have impaired angiogenic potential and the number of circulating CD31(+) cells were correlated with CV risk. These findings may contribute to the understanding of the pathogenesis of CAD.
| S-EPMC4224564 | biostudies-other
Project description:Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis.To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk.Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45(med+) blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death. There was an inverse association between CD34(+) and CD34(+)/CD133(+) cell counts and risk of death in cohort 1 (?=-0.92, P=0.043 and ?=-1.64, P=0.019, respectively) that was confirmed in cohort 2 (?=-1.25, P=0.020 and ?=-1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34(+)/CD133(+) cell counts improved risk prediction metrics beyond standard risk factors.Reduced circulating progenitor cell counts, identified primarily as CD34(+) mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies.
| S-EPMC4715427 | biostudies-literature
Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis In total 153 arrays were analyzed with 6 technical replicates (147 biological samples). CD34+ stem cells, CD4+ T-cells, resting CD14+ monocytes, stimulated monocytes and macrophages were analyzed, all from patient with severe coronary atherosclerosis or controls that had no coronary atherosclerosis as determined angiographically, and which were carefully matched for age and gender.
2008-12-01 | E-GEOD-9820 | biostudies-arrayexpress
Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis
2008-12-01 | GSE9820 | GEO
Project description:Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, leukocytes have a hyperinflammatory phenotype. We hypothesize that immune cell reprogramming in these patients occurs at the level of myeloid progenitors. We included 13 patients with coronary artery disease due to severe atherosclerosis and 13 subjects without atherosclerosis in an exploratory study. Cytokine production capacity after ex vivo stimulation of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs was higher in patients with atherosclerosis. In BM-MNCs this was associated with increased glycolysis and oxidative phosphorylation. The BM composition was skewed towards myelopoiesis and transcriptome analysis of HSC/GMP cell populations revealed enrichment of neutrophil- and monocyte-related pathways. These results show that in patients with atherosclerosis, activation of innate immune cells occurs at the level of myeloid progenitors, which adds exciting opportunities for novel treatment strategies.
| S-EPMC7665893 | biostudies-literature
Project description:ImportanceStem and progenitor cells mobilize from the bone marrow in response to myocardial ischemia. However, the association between the change in circulating progenitor cell (CPC) counts and disease prognosis among patients with ischemia is unknown.ObjectiveTo investigate the association between the change in CPC counts during stress testing and the risk of adverse cardiovascular events in patients with stable coronary artery disease (CAD).Design, setting, and participantsThis prospective cohort study included a population-based sample of 454 patients with stable CAD who were recruited between June 1, 2011, and August 15, 2014, at Emory University-affiliated hospitals and followed up for 3 years. Data were analyzed from September 15, 2018, to October 15, 2018.ExposuresMyocardial perfusion imaging with technetium Tc 99m sestamibi at rest and 30 to 60 minutes after conventional stress testing.Main outcomes and measuresCirculating progenitor cells were enumerated with flow cytometry as CD34-expressing mononuclear cells (CD45med/CD34+), with additional quantification of subsets coexpressing the chemokine (C-X-C motif) receptor 4 (CD34+/CXCR4+). Changes in CPC counts were calculated as poststress minus resting CPC counts. Cox proportional hazards regression models were used to identify factors associated with the combined end point of cardiovascular death and myocardial infarction after adjusting for clinical covariates, including age, sex, race, smoking history, body mass index, and history of heart failure, hypertension, dyslipidemia, and diabetes.ResultsOf the 454 patients (mean [SD] age, 63 [9] years; 76% men) with stable CAD enrolled in the study, 142 (31.3%) had stress-induced ischemia and 312 (68.7%) did not, as measured by single-photon emission computed tomography. During stress testing, patients with stress-induced ischemia had a mean decrease of 20.2% (interquartile range [IQR], -45.3 to 5.5; P?<?.001) in their CD34+/CXCR4+ counts, and patients without stress-induced ischemia had a mean increase of 3.2% (IQR, -20.6 to 35.1; P?<?.001) in their CD34+/CXCR4+ counts. Twenty-four patients (5.2%) experienced adverse events. After adjustment, baseline CPC counts were associated with worse adverse outcomes, but this association was not present after stress-induced ischemia was included in the model. However, the change in CPC counts during exercise remained significantly associated with adverse events (hazard ratio, 2.59; 95% CI, 1.15-5.32, per 50% CD34+/CXCR4+ count decrease), even after adjustment for clinical variables and the presence of ischemia. The discrimination of risk factors associated with incident adverse events improved (increase in C statistic from 0.72 to 0.77; P?=?.003) with the addition of the change in CD34+/CXCR4+ counts to a model that included clinical characteristics, baseline CPC count, and ischemia.Conclusions and relevanceIn this study of patients with CAD, a decrease in CPC counts during exercise is associated with a worse disease prognosis compared with the presence of stress-induced myocardial ischemia. Further studies are needed to evaluate whether strategies to improve CPC responses during exercise stress will be associated with improvements in the prognosis of patients with CAD.
| S-EPMC6902161 | biostudies-literature
Project description:BackgroundCirculating endothelial cells (CECs) are widely reported as a promising biomarker of endothelial damage/dysfunction in coronary artery disease (CAD). The two popular methods of CEC quantification include the use of immunomagnetic beads separation (IB) and flow cytometry analysis (FC); however, they suffer from two main shortcomings that affect their diagnostic and prognostic responses: non-specific bindings of magnetic beads to non-target cells and a high degree of variability in rare cell identification, respectively. We designed a microfluidic chip with spatially staggered micropillars for the efficient harvesting of CECs with intact cellular morphology in an attempt to revisit the diagnostic goal of CEC counts in CAD patients with angina pectoris.MethodsA label-free microfluidic assay that involved an in-situ enumeration and immunofluorescent identification (DAPI+/CD146+/VEGFR1+/CD45-) of CECs was carried out to assess the CEC count in human peripheral blood samples. A total of 55 CAD patients with angina pectoris [16 with chronic stable angina (CSA) and 39 with unstable angina (UA)], together with 15 heathy controls (HCs) were enrolled in the study.ResultsCEC counts are significantly higher in both CSA and UA groups compared to the HC group [respective medians of 6.9, 10.0 and 1.5 cells/ml (p < 0.01)]. Further, a significant elevation of CEC count was observed in the three UA subgroups [low risk (5.3) vs. intermediate risk (10.8) vs. high risk (18.0) cells/ml, p < 0.001) classified in accordance to the TIMI NSTEMI/UA risk score system. From the receiver-operating characteristic curve analysis, the AUCs for distinguishing CSA and UA from HC were 0.867 and 0.938, respectively. The corresponding sensitivities were 87.5% and 84.6% and the specificities were 66.7% and 86.7%, respectively.ConclusionsOur microfluidic assay system is efficient and stable for CEC capture and enumeration. The results showed that the CEC count has the potential to be a promising clinical biomarker for the assessment of endothelial damage/dysfunction in CAD patients with angina pectoris.
| S-EPMC5509377 | biostudies-literature
Project description:Background Deoxycholic acid (DCA) is a secondary bile acid that may promote vascular calcification in experimental settings. Higher DCA levels were associated with prevalent coronary artery calcification (CAC) in a small group of individuals with advanced chronic kidney disease. Whether DCA levels are associated with CAC prevalence, incidence, and progression in a large and diverse population of individuals with chronic kidney disease stages 2 to 4 is unknown. Methods and Results In the CRIC (Chronic Renal Insufficiency Cohort) study, we evaluated cross-sectional (n=1057) and longitudinal (n=672) associations between fasting serum DCA levels and computed tomographic CAC using multivariable-adjusted regression models. The mean age was 57±12 years, 47% were women, and 41% were Black. At baseline, 64% had CAC (CAC score >0 Agatston units). In cross-sectional analyses, models adjusted for demographics and clinical factors showed no association between DCA levels and CAC >0 compared with no CAC (prevalence ratio per 1-SD higher log DCA, 1.08 [95% CI, 0.91-1.26). DCA was not associated with incident CAC (incidence per 1-SD greater log DCA, 1.08 [95% CI, 0.85-1.39]) or CAC progression (risk for increase in ≥100 and ≥200 Agatston units per year per 1-SD greater log DCA, 1.05 [95% CI, 0.84-1.31] and 1.26 [95% CI, 0.77-2.06], respectively). Conclusions Among CRIC study participants, DCA was not associated with prevalent, incident, or progression of CAC.
| S-EPMC9075491 | biostudies-literature