Abstract 16284: Patient Derived Endothelial Progenitor Cells as a Model to Unravel New Mechanisms of Coronary Artery Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Meghan Finemore ◽  
Christine Yu ◽  
Kristen J Bubb ◽  
Katherine Kott ◽  
Belinda Di Bartolo ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Pearson Correlation ◽  
Spontaneous Growth ◽  
Individual Susceptibility ◽  
Artery Disease ◽  
The Impact

Introduction: Endothelial colony forming cells (ECFCs) are progenitor cells that can differentiate into mature endothelial cells. Ability to culture these cells from peripheral blood mononuclear cells (PBMCs) make them a suitable tool for investigation into individual susceptibility to coronary artery disease (CAD). We hypothesise that patient-derived ECFCs provide a model to study endothelial cell signalling in patients with CAD. Here we aim to identify biasing factors in spontaneous growth of ECFCs, and confirm whether they retain an “imprint” of patient disease burden. Methods: ECFCs were purified from patient samples in the BioHEART-CT biobank. Mitochondrial ROS assays (MitoSOX) were performed and protein lysate was collected to determine expression of redox signalling proteins by immunoblotting. CT coronary angiograms were analysed using Gensini scores to determine the burden of disease. Results: Spontaneous growth of ECFCs occurred in 178 of the 828 patients (21.50%). Spontaneous growth was lower in those with obesity (BMI ≥ 30: 15.7%, n = 30/191 vs BMI < 30: 23.2%, n = 148/637, p = 0.03) and higher in hypertensive patients (25.4% n = 81/319 vs normotensive 19.1% n = 97/509, p = 0.03), although growth was not affected by presence of CAD (21.0% n = 59/281 vs CAD- 21.8% n = 119/547, p = 0.8). ECFCs expressed endothelial markers such as CD31 and eNOS, validating their differentiation into endothelial cells. However, ECFCs of patients with CAD expressed higher NADPH oxidase-2 protein level (1.9±0.4 fold-change vs CAD-, n = 13, p = 0.02) and were associated with higher mitochondrial superoxide production (Pearson correlation= 0.66, n = 18, p = 0.003). Conclusion: Spontaneous growth is affected by obesity and hypertension however the impact of this is reasonably small. The biochemical characteristics identified in these cells correlate with the patient’s disease state indicating that they are a helpful tool to further investigate individual susceptibility to CAD.

scholarly journals Determination of Early and Late Endothelial Progenitor Cells in Peripheral Circulation and Their Clinical Association with Coronary Artery Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Shotoku Tagawa ◽  
Chiaki Nakanishi ◽  
Masayuki Mori ◽  
Tsuyoshi Yoshimuta ◽  
Shohei Yoshida ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mononuclear Cells ◽  
Peripheral Circulation ◽  
Control Group ◽  
Endothelial Progenitor ◽  
Artery Disease

The clinical implications of early and late endothelial progenitor cells (EPCs) in coronary artery disease (CAD) remain unclear. We investigated endothelial dysfunction in CAD by simultaneously examining early and late EPC colony formation and gene expression of specific surface markers in EPCs. EPCs were extracted from a total of 83 subjects with (n=47) and without (n=36) CAD. Early and late EPC colonies were formed from mononuclear cells extracted from peripheral blood. We found that fewer early EPC colonies were produced in the CAD group (7.2 ± 3.l/well) than those in the control group (12.4 ± 1.4/well,p<0.05), and more late EPC colonies were produced in the CAD group (0.8 ± 0.2/well) than those in the control group (0.25 ± 0.02/well,p<0.05). In the CAD group, the relative expression of CD31 and KDR of early and late EPCs was lower than in the control group. These results demonstrate that CAD patients could have increased late EPC density and that early and late EPCs in CAD patients exhibited immature endothelial characteristics. We suggest that changes in EPC colony count and gene expression of endothelial markers may have relation with development of CAD.

scholarly journals Shear stress improves the endothelial progenitor cell function via the CXCR7/ERK pathway axis in the coronary artery disease cases

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hua Zhou ◽  
Qiang Tu ◽  
Yan Zhang ◽  
Hua Qiang Xie ◽  
Qing Yun Shuai ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Shear Stress ◽  
Coronary Artery ◽  
Mononuclear Cells ◽  
Tube Formation ◽  
Endothelial Progenitor ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Artery Disease ◽  
The Impact

Abstract Background Dysfunction in the late Endothelial Progenitor Cells (EPCs) is responsible for endothelial repair in patients with Coronary Artery Disease (CAD), and the shear stress is beneficial for EPCs function. However, the impact of shear stress on the capacity of EPCs in CAD patients has not been elucidated yet. The C-X-C chemokine receptor 7/extracellular signal-regulated kinase (CXCR7)/(ERK) pathways are identified to regulate EPCs function in CAD patients. Here, we hypothesize that shear stress upregulates the CXCR7/ERK pathways, which restore the EPCs function in CAD patients. Methods The human Peripheral Blood Mononuclear Cells (PBMCs) were collected from healthy adults and CAD patients and then used for EPCs cultivation. The Lv-siRNA for human CXCR7 was transfected into induced EPCs isolated from the CAD patients. Meanwhile, the EPCs from CAD patients were subjected to shear stress generated by a biomimetic device. Next, the cell viability, migration, tube formation, and apoptosis were detected by CCK-8, Transwell assay, Matrigel, and flow cytometry, respectively. Also, the CXCR7/ERK pathways in human EPCs were analyzed by Western blotting and qRT-PCR. Result Compared to the EPCs collected from normal adults, the CAD patient-derived EPCs showed reduced in vitro vasculogenic capacity. Also, the level of CXCR7 in CAD patient-derived EPCs was significantly reduced compared to the EPCs of healthy subjects. Meanwhile, the extracellular signal-regulated kinase (ERK), which represents a CXCR7 downstream signaling pathway, had decreased phosphorylation level. The shear stress treatment augmented the CXCR7 expression and also elevated ERK phosphorylation, which is comparable to the up-regulation of CAD patient-derived EPCs function. Further, the small interfering RNA (siRNA)-mediated CXCR7 knockdown diminished the enhanced migration, adhesion, and tube formation capacity of shear stress treated CAD patient-derived EPCs. Conclusion Up-regulation of the CXCR7/ERK pathways by shear stress can be a promising new target in enhancing the vasculogenic ability of CAD patient-derived EPCs.

Associations Between Inflammation, Cardiovascular Regenerative Capacity, and Cardiovascular Events: A Cohort Study

2021 ◽  
Author(s):  
Zakaria Almuwaqqat ◽  
Jeong Hwan Kim ◽  
Mariana Garcia ◽  
Yi-An Ko ◽  
Kasra Moazzami ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Stable Coronary Artery Disease ◽  
High Sensitivity ◽  
Regenerative Capacity ◽  
Risk Of Death ◽  
Artery Disease

Objective: Circulating progenitor cells possess immune modulatory properties and might mitigate inflammation that is characteristic of patients with coronary artery disease. We hypothesized that patients with fewer circulating progenitor cells (CPCs) will have higher inflammatory markers and worse outcomes. Approach and Results: Patients with stable coronary artery disease were enrolled in a prospective study enumerating CPCs as CD (cluster of differentiation)-34–expressing mononuclear cells (CD34+) and inflammation as levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein) levels. Patients were followed for 5 years for the end points of death and myocardial infarction with repeat inflammatory biomarkers measured after a median of 2 years. In the entire cohort of 392 patients, IL-6 and high-sensitivity CRP levels remained unchanged (0.3±2.4 pg/mL and 0.1±1.0 mg/L; P =0.45) after 2 years. CPC counts (log-transformed) were inversely correlated with the change in IL-6 levels (r, −0.17; P <0.001). Using linear regression, IL-6 and high-sensitivity CRP levels declined by −0.59 (95% CI, −0.90 to −0.20) pg/mL and −0.13 (−0.28 to 0.01) mg/L per 1 log higher CPC counts after adjustment for the demographic and clinical variables, as well as medications. Using Cox models adjusted for these risk factors, a rise in 1 pg/mL of IL-6 was associated with a 11% (95% CI, 9–13) greater risk of death/myocardial infarction. We found that the change in IL6 level partly (by 40%) mediated the higher risk of adverse events among those with low CPC counts. Conclusions: Reduced cardiovascular regenerative capacity is independently associated with progressive inflammation in patients with coronary artery disease that in turn is associated with poor outcomes.

The Impact of Smoking on Cardiovascular Outcomes and Comorbidities in Statin-treated Patients with Coronary Artery Disease: A Post hoc Analysis of the GREACE Study

2013 ◽  
Vol 11 (5) ◽  
pp. 779-784 ◽  
Author(s):  
Vasilios G. Athyros ◽  
Konstantinos Tziomalos ◽  
Niki Katsiki ◽  
Thomas D. Gossios ◽  
Olga Giouleme ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Outcomes ◽  
Post Hoc Analysis ◽  
Artery Disease ◽  
Post Hoc ◽  
The Impact

scholarly journals Impact of Coronary CT angiography in combination with CAD-RADS on the management of coronary artery disease patients

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
F Andre ◽  
S Seitz ◽  
P Fortner ◽  
R Sokiranski ◽  
F Gueckel ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Stratification ◽  
Coronary Ct Angiography ◽  
Patient Management ◽  
Male Gender ◽  
Coronary Ct ◽  
History Of ◽  
Artery Disease ◽  
The Impact

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Siemens Healthineers Introduction Coronary CT angiography (CCTA) plays an increasing role in the detection and risk stratification of patients with coronary artery disease (CAD). The Coronary Artery Disease – Reporting and Data System (CAD-RADS) allows for standardized classification of CCTA results and, thus, may improve patient management. Purpose Aim of this study was to assess the impact of CCTA in combination with CAD-RADS on patient management and to identify the impact of cardiovascular risk factors (CVRF) on CAD severity. Methods CCTA was performed on a third-generation dual-source CT scanner in patients, who were referred to a radiology centre by their attending physicians. In a total of 4801 patients, CVRF were derived from medical reports and anamnesis. Results The study population consisted of 4770 patients (62.0 (54.0-69.0) years, 2841 males) with CAD (CAD-RADS 1-5), while 31 patients showed no CAD and were excluded from further analyses. Age, male gender and the number of CVRF were associated with more severe CAD stages (all p &lt; 0.001). 3040 patients (63.7 %) showed minimal or mild CAD requiring optimization of CVRF i.e. medical therapy but no further assessment at his time. A group of 266 patients (5.6 %) had a severe CAD defined as CAD-RADS 4B/5. In the multivariate regression analysis, age, male gender, history of smoking, diabetes mellitus and hyperlipidaemia were significant predictors for severe CAD, whereas arterial hypertension and family history of CAD did not reach significance. Of note, a subgroup of 28 patients (10.5 %) with a severe CAD (68.5 (65.5-70.0) years, 26 males, both p = n.s.) had no CVRF. Conclusions CCTA in combination with the CAD-RADS allowed for effective risk stratification of CAD patients. The majority of the patients showed non-obstructive CAD and, thus, could be treated conservatively without the need for further CAD assessment. CVRF out of arterial hypertension and family history had an impact on CAD severity reflected in higher CAD-RADs gradings. Of note, a relevant fraction of patients with CAD did not have any CVRF and, thus, may not be covered by risk stratification models. CAD-RADS n Age (years) Males (%) 1 1453 56.0 (50.0-62.0) 623 (42.9 %) 2 1587 62.0 (55.0-69.0) 918 (57.8 %) 3 1067 66.0 (59.0-71.0) 749 (70.2 %) 4A 397 66.0 (59.0-72.0) 317 (79.8 %) 4B 162 67.0 (61.0-74.0) 139 (85.8 %) 5 104 66.0 (58.5.0-77.0) 95 (91.3 %)

scholarly journals Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease

2021 ◽  
Author(s):  
Rutao Wang ◽  
Scot Garg ◽  
Chao Gao ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Revascularization ◽  
Long Term Outcomes ◽  
Vital Status ◽  
Increased Risk ◽  
Artery Disease ◽  
The Impact

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

scholarly journals Impact of Coronary Artery Disease and Diabetes Mellitus on the Long-Term Follow-Up in Patients after Retrograde Recanalization of the Femoropopliteal Arterial Region

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Joanna Wojtasik-Bakalarz ◽  
Zoltan Ruzsa ◽  
Tomasz Rakowski ◽  
Andreas Nyerges ◽  
Krzysztof Bartuś ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Of Death ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Artery Disease ◽  
The Impact

The most relevant comorbidities in patients with peripheral artery disease (PAD) are coronary artery disease (CAD) and diabetes mellitus (DM). However, data of long-term follow-up of patients with chronic total occlusion (CTO) are scarce. The aim of the study was to assess the impact of CAD and DM on long-term follow-up patients after superficial femoral artery (SFA) CTO retrograde recanalization. In this study, eighty-six patients with PAD with diagnosed CTO in the femoropopliteal region and at least one unsuccessful attempt of antegrade recanalization were enrolled in 2 clinical centers. Mean time of follow-up in all patients was 47.5 months (±40 months). Patients were divided into two groups depending on the presence of CAD (CAD group: n=45 vs. non-CAD group: n=41) and DM (DM group: n=50 vs. non-DM group: n=36). In long-term follow-up, major adverse peripheral events (MAPE) occurred in 66.6% of patients with CAD vs. 36.5% of patients without CAD and in 50% of patients with DM vs. 55% of non-DM subjects. There were no statistical differences in peripheral endpoints in both groups. However, there was a statistically significant difference in all-cause mortality: in the DM group, there were 6 deaths (12%) (P value = 0.038). To conclude, patients after retrograde recanalization, with coexisting CTO and DM, are at higher risk of death in long-term follow-up.

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