The Impact of a Single Apheretic Procedure on Endothelial Function Assessed by Peripheral Arterial Tonometry and Endothelial Progenitor Cells

Introduction: Drug-eluting stents (DESs) are replacing bare-metal stents (BMSs), but in-stent restenosis (ISR) remains a problem. Impaired endothelial function is a key event in the atherosclerosis process and a predictor of future cardiovascular events. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry (PAT) evaluates endothelial function noninvasively. Hypothesis: We prospectively assessed the prognostic value of RHI in predicting ISR after percutaneous coronary intervention (PCI). Methods: RHI was measured using Endo-PAT 2000 before PCI (initial RHI) and at follow-up angiography (F/U RHI) in 249 consecutive patients who had successful PCI. F/U angiography was performed at six and nine months after PCI with BMS and DES, respectively. ISR was defined as percent diameter stenosis >50% at F/U angiography assessed by quantitative coronary angiography. Results: At F/U, ISR was seen in 68 patients (27.3%). F/U ln(RHI) was significantly lower in patients with ISR than in those without (0.52 ± 0.23 vs. 0.65 ± 0.27, p < 0.01); no between-group difference in initial ln(RHI) was seen (0.60 ± 0.26 vs. 0.62 ± 0.25, p = 0.56). By multivariate logistic regression analysis, even after adjusting for other significant parameters in univariate analysis (BMS use, total stent length, HDL-Cholesterol, HbA1c, calcium antagonist use, and post-PCI minimum lumen diameter), F/U ln(RHI) independently predicted ISR (odds ratio: 0.13; 95% confidence interval [CI]: 0.04-0.48; p = 0.002). In receiver operating-characteristic analysis, F/U RHI was the strongest predictor of ISR (area under the curve [AUC]: 0.67; 95% CI: 0.60-0.75; p < 0.01; RHI < 1.73 had 67.6% sensitivity, 64.1% specificity); AUC significantly improved from 0.62 to 0.70 when RHI was added to traditional ISR risk factors (diabetes mellitus, total stent length, minimum stent diameter) (p = 0.02). Net reclassification index was significant after addition of RHI (26.5%, p = 0.002). Conclusions: To our knowledge, this is the first study indicating that impaired RHI at F/U angiography independently predicts occurrence of ISR. The simple and noninvasive assessment of endothelial function by RH-PAT adds incremental prognostic value to ISR-risk stratification following PCI.

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Abstract 3698: Decreased Circulating Endothelial Progenitor Cells and Endothelial Dysfunction: a Novel Mechanism of Atherogenesis in Obesity.

Circulation ◽

10.1161/circ.116.suppl_16.ii_839-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Paulo F Leite ◽

Claudia R Andrade ◽

Santa Poppe ◽

Luiz A Cesar ◽

Silmara Coimbra ◽

...

Keyword(s):

Metabolic Syndrome ◽

Multivariate Analysis ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Obese Patients ◽

Endothelial Progenitor ◽

Circulating Endothelial Progenitor Cells ◽

Morbid Obese

Underlying mechanisms of endothelial dysfunction in obesity are not fully understood. Circulating Endothelial Progenitor Cells (EPCs) are known to promote endothelial repair. Our aim was to assess the number/function of EPCs in morbid obese individuals and its correlation with endothelial function and inflammatory markers. EPCs were isolated from 33 morbid obese patients (age 47±1.8 y; men=34%; BMI=49±2.1 kg/m 2 , metabolic syndrome=84%) and 20 lean controls. Peripheral blood EPC number was significantly reduced in obese patients both with flow cytometry (KDR + /CD34 + ; 0.041±0.04 vs 0.074±0.05 %events, p<0.001) and fluorescence analysis after short-term culture (49±4 vs 28±2 cells/field, p<0.001). The plasma number of primitive CD 133 + cells, and concentrations of VEGF (Elisa) and nitrogen oxides (which potentially recruit EPCs), were similar to control, suggesting that reduction of EPCs occurs distally to early cell differentiation. Importantly, C-Reactive Protein (CRP), robustly increased in obese patients (0.15±0.04 vs 1.3±0.3; p=0.003), was a strong predictor of reduced EPC number at multivariate analysis (r=0.623; p < 0.001). Likewise, the migratory response of EPCs to VEGF in vitro was significantly impaired in obese vs controls, despite similar VEGF receptor numbers. Multivariate analysis suggested potential roles of metabolic syndrome and leptin in such effect. Endothelial function at flow-mediated brachial artery reactivity was markedly reduced (by 60%) in obese patients, and had a significant inverse correlation with EPC number (r= 0.678; p< 0.001). Carotid intimal thickness was also increased in obese patients (0.68±0.02 vs 0.58±0.08; p=0.001). On the other hand, the number of circulating endothelial cells (CD31 + /CD106 + ) was similar in both groups, suggesting that apoptosis was not enhanced in the obese. These results suggest for the first time that reduced number and migratory capacity of EPCs correlate with endothelial dysfunction or increased CRP and may be a key underlying mechanism of vascular complications and atherosclerosis in obesity.

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Abstract 536: Poor Correlation Between FMD and PAT-Ratio in Patients With Metabolic Syndrome

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.536 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Ueda Tomohiro

Keyword(s):

Metabolic Syndrome ◽

Endothelial Function ◽

Multivariable Analysis ◽

Control Group ◽

Poor Correlation ◽

Study Group ◽

Peripheral Arterial Tonometry ◽

Arterial Tonometry ◽

Coronary Lesions ◽

Peripheral Arterial

Background: Flow mediated dilatation (FMD) and peripheral arterial tonometry (PAT) are commonly used methods for assessing endothelial function in a research setting but it is unclear how well they correlate. The aim of this study is to compare and correlate these methods in patients with metabolic syndrome. Methods: The study involved 105 subjects (mean age68±10 years) with metabolic syndrome. Based on the results of coronary angiography, they were divided into 2 groups: a study group with coronary lesions (n=68) and a control group without coronary lesions (n=37). Flow mediated vasodilatation (FMD) and nitroglycerine-induced vasodilatation (NID) in the brachial artery was measured by using UNEXEF18G (UNEX CO, Japan). At the same time, PAT ratio was measured by using Endo-PAT 2000 (Itamar Medical, Israel) Results: FMD was not correlated with PAT ratio by Spearman`s analysis. FMD was significantly impaired in the study group compared to that in the control group (3.9±1.8% vs. 2.6±1.5%, respectively; P<0.001). However, NID and PAT ratio had no deference in the two groups. Multivariable analysis revealed that FMD (odds ratio: 0.53, 95% confidence interval [CI]: 0.31-0.90) were independent variables for CAD in metabolic syndrome patients. Conclusion: This study showed that poor correlation between FMD and PAT in patients with metabolic syndrome. PAT may not be used as a substitute for FMD as a measure of endothelial function

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Intra-carotid arterial transfusion of circulatory-derived autologous endothelial progenitor cells in rodent after ischemic stroke — evaluating the impact of therapeutic time points on prognostic outcomes

10.21203/rs.2.23279/v2 ◽

2020 ◽

Author(s):

Kun-Chen Lin ◽

Han-Tan Chai ◽

Kuan-Hung Chen ◽

Pei‐Hsun Sung ◽

John Y. Chiang ◽

...

Keyword(s):

Ischemic Stroke ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Optimal Time ◽

Control Group ◽

Endothelial Progenitor ◽

Group 2 ◽

The Impact ◽

Carotid Arterial ◽

Group 1

Abstract Background: This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and Results: Adult-male SD rats (n=70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2x106 cells/by LICA administration 3h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS) and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain-infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2 and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all p<0.0001). By day 60, the endothelial cell markers at protein and cellular levels, and number of small vessels exhibited an opposite pattern of BIV among the groups (all p<0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy and apoptosis, were highest in group 2, lowest in group 1 and progressively increased from groups 3 to 7 (all p<0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all p<0.0001). Conclusion: Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.

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