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Sandra Erbs

Publications and source records attributed to Sandra Erbs.

At least 19 recordsLinked to original sources
PubMed2006

Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial.

AIMS: To investigate the clinical outcome after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Using a double-blind, placebo-controlled multicentre trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone-marrow-derived progenitor cells (BMCs) or placebo medium into the infarct artery 3-7 days after successful infarct reperfusion therapy. At 12 months, the pre-specified cumulative endpoint of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (P=0.009). Likewise, the combined endpoint death, recurrence of myocardial infarction, and rehospitalization for heart failure was significantly (P=0.006) reduced in patients receiving intracoronary BMC administration. Intracoronary administration of BMC remained a significant predictor of a favourable clinical outcome by Cox regression analysis, adjusting for classical predictors of poor outcome after AMI. CONCLUSION: Intracoronary administration of BMCs is associated with a significant reduction of the occurrence of major adverse cardiovascular events after AMI. Large-scale studies are warranted to confirm the effects of BMC administration on mortality and morbidity in patients with AMIs.

Adolescent↗
PubMed2006

Myocardial expression of Murf-1 and MAFbx after induction of chronic heart failure: Effect on myocardial contractility.

OBJECTIVE: In chronic heart failure (CHF) the myocardial expression of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha), which is thought to contribute to myocardial remodeling, was found to be increased. However, it is unknown whether the E3-ubiquitin ligases MAFbx and Murf-1 are involved in this remodeling process and whether their expression is regulated by TNF-alpha. METHODS: Rats underwent ligation of the left coronary artery to induce CHF or were sham-operated. The expression of MAFbx/Murf-1 and troponin I was analyzed by RT-PCR and Western blotting in the non-infarcted area of the left ventricle. In cell culture experiments the potency of TNF-alpha to stimulate Murf-1/MAFbx expression, the intracellular signaling pathway, and the involvement of the E3-ligases for the impairment of contractility were assessed. RESULTS: In CHF the myocardial expression of TNF-alpha was elevated 3.1-fold as compared to control. This was associated with a 4.5-fold and 2.7-fold increase in MAFbx and Murf-1 expression, respectively. A positive correlation between TNF-alpha and the expression of MAFbx or Murf-1 was evident. In neonatal rat cardiomyocytes, TNF-alpha induced the expression of MAFbx through p38MAPK-dependent pathways, whereas the induction of Murf-1 required the activation of the p42/44 MAPK pathway. Exposure of cardiomyocytes to TNF-alpha resulted in troponin I ubiquitinylation, subsequent degradation, and a decline in contractility. This was completely abrogated by siRNAs against Murf-1/MAFbx. CONCLUSION: TNF-alpha, which is increasingly expressed in CHF, induces troponin I degradation through a MAFbx/Murf-1-dependent pathway. This was associated with an impairment of contractility and might be one mechanism involved in the adverse remodeling process in CHF.

Animals↗
PubMed2006

Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.

BACKGROUND: Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction. METHODS: In a multicenter trial, we randomly assigned 204 patients with acute myocardial infarction to receive an intracoronary infusion of progenitor cells derived from bone marrow (BMC) or placebo medium into the infarct artery 3 to 7 days after successful reperfusion therapy. RESULTS: At 4 months, the absolute improvement in the global left ventricular ejection fraction (LVEF) was significantly greater in the BMC group than in the placebo group (mean [+/-SD] increase, 5.5+/-7.3% vs. 3.0+/-6.5%; P=0.01). Patients with a baseline LVEF at or below the median value of 48.9% derived the most benefit (absolute improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year, intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death, recurrence of myocardial infarction, and any revascularization procedure (P=0.01). CONCLUSIONS: Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction. Large-scale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality.

Aged↗
PubMed2006

Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress: the EPAS trial.

BACKGROUND: Statins and angiotensin type 1 (AT1) receptor blockers reduce cardiovascular mortality and morbidity. In the Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress (EPAS) trial, impact of independent or combined statin and AT1 receptor blocker therapy on endothelial expression of anti-atherosclerotic and proatherosclerotic genes and endothelial function in arteries of patients with coronary artery disease were tested. METHODS AND RESULTS: Sixty patients with stable coronary artery disease undergoing elective coronary artery bypass grafting (CABG) surgery were randomized 4 weeks before surgery to: (A) control without inhibition of renin-angiotensin system or statin; (B) statin (pravastatin 40 mg/d); (C) AT1 blockade (irbesartan 150 mg/d); or (D) combination of statin and AT1 blocker in same dosages. Primary end point was a priori therapy-dependent regulation of an anti-atherosclerotic endothelial expression quotient Q including mRNA expression (in arbitrary units measured by real-time polymerase chain reaction) of endothelial nitric oxide synthase and C-type natriuretic peptide, divided by expression of oxidized low-density lipoprotein receptor LOX-1 and NAD(P)H oxidase subunit gp91phox in left internal mammary arteries biopsies obtained by CABG surgery; 49 patients completed the study. Statin therapy increased lnQ from 3.2+/-0.4 to 4.4+/-0.4 significantly versus control. AT(1) blockade showed a trend to increase lnQ to 4.2+/-0.5. Combination of statin and AT1 blocker further increased lnQ to 5.1+/-0.6, but a putative interaction of both therapies in lnQ was not significant. Furthermore, preoperative therapy with statin, AT1 blocker and their combination improved endothelial function in internal mammary artery rings. CONCLUSIONS: Statin and AT1 blocker therapy independently and in combination improve an anti-atherosclerotic endothelial expression quotient and endothelial function.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Effects of exercise training on mortality in patients with coronary heart disease.

Endothelial dysfunction not only precedes the development of significant coronary artery stenosis, it has also been identified as a general phenomenon predicting future cardiovascular events in patients who are at risk. As regular physical activity as a part of a multifactorial intervention has been shown to affect symptoms beneficially, increase myocardial perfusion and--most importantly--reduce mortality in patients with coronary heart disease or myocardial infarction, this review will elucidate potential mechanisms responsible for the improvement in survival as a result of regular physical activity. The importance of exercise training-mediated regression of coronary stenosis, collateral formation, correction of endothelial dysfunction including the adaptation at the molecular level, as well as vasculogenesis will be discussed as possible underlying key players, and their potential contribution to the training-induced survival benefit in patients with coronary heart disease will be critically evaluated.

Coronary Circulation↗
PubMed2006

Both T-786C and G894T polymorphism of endothelial nitric oxide synthase affect in-vitro endothelium-dependent relaxation of internal mammary artery rings from patients with coronary artery disease.

OBJECTIVES: Polymorphisms of endothelial nitric oxide synthase (eNOS) gene in the promoter (T-786C) and exon 7 (G894T) have been suggested to attenuate endothelial function. As it is unknown whether these polymorphisms, on top of classical risk factors, further deteriorate endothelium-dependent vasomotion, we aimed to elucidate the impact of both polymorphisms on the ex-vivo vasomotor function of left internal mammary artery rings from patients with coronary artery disease (CAD) undergoing coronary bypass surgery (CABG). METHODS: Mammary artery rings from 51 consecutive patients with CAD were obtained during elective CABG. Endothelium-dependent ring relaxation was measured in vitro in an organ chamber using acetylcholine (10 to 3 x 10 mol/l). Polymorphisms were determined by polymerase chain reaction restriction length polymorphism. RESULTS: Thirty-three per cent of patients were positive for the T-786C polymorphism, 25% for the G894T polymorphism, and 18% carried mutated alleles in both loci. Maximal acetylcholine-induced ring relaxation was 46.7+/-3.2% in T-786C, 59.6+/-4.2% in G894T, and 66.7+/-7.4% in T-786C/G894T compared with 94.9+/-2.0% in wild-type subjects (P<0.05 versus T-786C, G894T, T-786C/G894T). Patients positive for an eNOS polymorphism with more than three cardiovascular risk factors displayed a further attenuation of acetylcholine-mediated relaxation (45+/-6 %) compared with having up to three risk factors (59+/-3%, P<0.05). CONCLUSION: In patients with CAD, in-vitro assessed endothelium-dependent relaxation of mammary arteries was significantly impaired in those positive for the T-786C or the G894T eNOS polymorphism. These results suggest that the presence of either one of the eNOS polymorphisms deteriorated endothelium-dependent vasodilatory capacity of large conduit vessels on top of classical risk factors in patients with CAD.

Aged↗
PubMed2005

Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study.

Transplantation of blood-derived circulating progenitor cells (CPC) has been shown to improve myocardial regeneration after myocardial infarction. It remains unclear whether CPC transplantation exerts beneficial effects also in patients with chronic myocardial ischemia. We initiated a randomized, double-blind, placebo-controlled study evaluating the impact of intracoronary infusion of CPCs on coronary vasomotion and left ventricular (LV) function in patients after recanalization of chronic coronary total occlusion (CTO). After recanalization of CTO, 26 patients (age, 63+/-2 years; LV ejection fraction, 53+/-2%) were randomly assigned to the treatment (intracoronary transplantation of CPCs) or control group. Coronary flow reserve in response to adenosine (2.4 mg/min) was measured in the target vessel at the beginning of the study and after 3 months. LV function and infarct size were assessed by MRI and metabolism by 18F deoxyglucose positron emission tomography. CPC application resulted in an increase in coronary flow reserve by 43% from 2.3+/-0.3 to 3.3+/-0.5 (P<0.05 versus beginning and control). At 3 months, the number of hibernating segments in the target region (from 2.9+/-0.6 to 2.0+/-0.6 segments, P<0.05 versus beginning and control) had declined in the treatment group, whereas no significant changes were observed in the control group. MRI revealed a reduction in infarct size by 16% and an increase in LV ejection fraction by 14% in the treatment group (from 51.7+/-3.7 to 58.9+/-3.2%; P<0.05 versus beginning and control) because of an augmented wall motion in the target region. Hence, intracoronary transplantation of CPCs after recanalization of CTO results in an improvement of macro- and microvascular function and contributes to the recruitment of hibernating myocardium.

Angioplasty, Balloon, Coronary↗
PubMed2005

Effects of exercise and ischemia on mobilization and functional activation of blood-derived progenitor cells in patients with ischemic syndromes: results of 3 randomized studies.

BACKGROUND: Exercise training (ET) has been shown to improve regional perfusion in ischemic syndromes. This might be partially related to a regeneration of diseased endothelium by circulating progenitor cells (CPCs) or CPC-derived vasculogenesis. The aim of the present study was to determine whether ischemic stimuli during ET are required to promote CPC mobilization in patients with cardiovascular diseases. METHODS AND RESULTS: Patients with peripheral arterial occlusive disease (PAOD) were randomized to 4 weeks of daily ischemic ET or control (group A). Successfully revascularized patients with PAOD were randomized to 4 weeks of daily nonischemic ET or control (group B). Patients with stable coronary artery disease were subjected to 4 weeks of subischemic ET or control (group C). At baseline and after 4 weeks, the number of KDR+/CD34+ CPCs was determined by fluorescence-activated cell sorting analysis. Levels of vascular endothelial growth factor (VEGF) were measured by ELISA. A Matrigel assay was used to quantify CPC integration into vascular structures. Expression of the homing factor CXCR4 was determined by reverse transcription-polymerase chain reaction. In group A only, ischemic ET increased VEGF levels by 310% (P<0.05 versus control) associated with an increase in CPCs by 440% (P<0.05 versus control), increased CXCR4 expression, and enhanced integration of CPCs into endothelial networks. In contrast, subischemic ET in groups B and C increased CXCR4 expression and CPC integration. CONCLUSIONS: In training programs, symptomatic tissue ischemia seems to be a prerequisite for CPC mobilization. However, ischemic and subischemic ET programs affect CXCR4 expression of CPCs, which might lead to an improved CPC integration into endothelial networks.

Aged↗
PubMed2005

Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia.

AIMS: Despite considerable advances in the therapy of patients with peripheral arterial occlusive disease (PAOD) and critical limb ischaemia (CLI), a substantial number remain, in whom amputation has to be considered the only and final option. Recent evidence from animal models of hind limb ischaemia suggests that neovascularization induced by circulating blood-derived progenitor cells (CPCs) may permit limb salvage. It remains unclear, however, whether an intra-arterial application of autologous CPCs in patients with infrapopliteal PAOD and CLI is safe, feasible, and of potentially beneficial effects. METHODS AND RESULTS: Seven patients with critical PAOD were treated with an intra-arterial infusion of autologous CPCs (39+/-24 x 10(6)) isolated from peripheral blood. Pre-interventional stimulation with G-CSF and CPC application was well tolerated. Twelve weeks after CPC administration, the pain-free walking distance increased from 6+/-13 to 195+/-196 m. A significant increase in the ankle-brachial index, transcutaneous O(2), flow-dependent vasodilation, flow reserve in response to adenosine, and endothelium-dependent vasodilation was observed. CONCLUSION: These preliminary data in a small series of patients with CLI without surgical or interventional options indicate that CPC application is safe, feasible, and may improve both functional and clinical indices.

Aged↗
PubMed2005

Antioxidative effects of exercise training in patients with chronic heart failure: increase in radical scavenger enzyme activity in skeletal muscle.

BACKGROUND: In chronic heart failure (CHF), cross-talk between inflammatory activation and oxidative stress has been anticipated in skeletal muscle (SM). The role of the radical scavenger enzymes superoxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GPX), which remove oxygen radicals, has never been assessed in the SM in this context. Moreover, it remains unknown whether exercise training augments the activity of these enzymes in CHF. METHODS AND RESULTS: Twenty-three patients with CHF were randomized to either 6 months of exercise training (T) or a sedentary lifestyle (C); 12 age-matched healthy subjects (HS) were studied in parallel. Activity of Cat, SOD, and GPX was assessed in SM biopsies before and after 6 months (6 months). Oxidative stress was determined by measuring nitrotyrosine formation. SOD, Cat, and GPX activity was reduced by 31%, 57%, and 51%, respectively, whereas nitrotyrosine formation was increased by 107% in SM in CHF (P<0.05 versus HS). In CHF, exercise training augmented GPX and Cat activity in SM by 41% (P<0.05 versus before and group C) and 42% (P<0.05 versus before and group C), respectively, and decreased nitrotyrosine production by 35% (from 3.8+/-0.4% tissue area before to 2.5+/-0.3% after 6 months; P<0.05 versus before). CONCLUSIONS: The reduced activity of major antioxidative enzymes in the SM of CHF patients is associated with increased local oxidative stress. Exercise training exerts antioxidative effects in the SM in CHF, in particular, due to an augmentation in activity of radical scavenger enzymes.

Case-Control Studies↗
PubMed2005

Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease.

BACKGROUND: In patients with stable coronary artery disease, physical exercise training (ET) improves endothelial dysfunction. A potential mechanism mediating the enhanced vasomotor function is a reduced breakdown of endothelium-derived nitric oxide by reactive oxygen species (ROS). The aim of the present study was to analyze the impact of ET on sources of ROS generation in the left internal mammary artery of patients with symptomatic coronary artery disease. METHODS AND RESULTS: In left internal mammary artery rings sampled during bypass surgery from 45 patients randomized to either a training (n=22) or an inactive control (n=23) group, the mRNA expression of NAD(P)H oxidase subunits, NAD(P)H oxidase activity, and ROS production were assessed. In addition, endothelial function, expression of angiotensin II (Ang II) receptor type 1 and 2 (AT1-R and AT2-R), and Ang II-mediated vasoconstriction were determined. ET resulted in a significant lower expression of gp91phox (23.1+/-0.5 versus 69.1+/-18.1 arbitrary units, training versus control), p22phox (0.7+/-0.3 versus 2.0+/-0.5 arbitrary units), and Nox4 (2.7+/-1.2 versus 5.4+/-1.0 arbitrary units). Enzymatic activity (2.1+/-0.3 versus 4.9+/-0.4 mU/mg) and ROS generation (0.02+/-0.01 versus 0.06+/-0.02 arbitrary units) were significantly lower in the training compared with the control group. On a functional level, ET resulted in improved acetylcholine-mediated vasodilatation and a 49% reduction in Ang II-induced vasoconstriction, accompanied by lower AT1-R (3.7+/-0.8 versus 16.6+/-5.7 arbitrary units, training versus control) and higher AT2-R (7.8+/-2.5 versus 1.6+/-0.7 arbitrary units) mRNA expression. CONCLUSIONS: ET reduces vascular expression of NAD(P)H oxidase and AT1-R, resulting in decreased local ROS generation. These molecular effects converge in a reduced Ang II-mediated vasoconstriction.

Aged↗
PubMed2005

Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells.

OBJECTIVE: Function and availability of circulating progenitor cells (CPC) have been shown to be impaired in patients with diabetes mellitus (DM). Therefore, the aim of the present study was to analyze possible mechanisms leading to the reduction of CPC amount and function. METHODS AND RESULTS: Peripheral blood mononuclear cells (MNCs) of healthy donors (n=15) were cultivated under hyperglycemia (HG) conditions (12 mmol/L D-Glucose) or in osmotic control medium (Con) (5 mmol/L D-Glucose plus 7 mmol/L L-Glucose) for 7 days. CPC amount was determined by uptake of acetylated low-density lipoprotein and lectin binding. On the functional level, cell cycle status, nitric oxide (NO) production, and migrational and integrative capacity of CPCs were assessed. HG conditions caused a significant decrease in CPC amount derived from healthy MNCs. Furthermore, HG conditions led to a functional impairment, reflected in a decreased NO production and matrix metalloproteinase (MMP)-9 activity, as well as an impairment of the migrational and integrative capacities. CONCLUSIONS: HG, a main feature of DM, affects important functional characteristics of CPCs. These results may provide further insight into the pathomechanism of endothelial dysfunction in HG.

Adolescent↗
PubMed2005

Effects of exercise training on insulin-like growth factor-I expression in the skeletal muscle of non-cachectic patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is associated with progressive muscle atrophy and reduced local expression of insulin-like growth factor I (IGF-I). DESIGN: The present study was designed to test the hypothesis that the local deficiency of IGF-I in the skeletal muscle of patients with CHF would respond to a 6-months aerobic training intervention. Therefore, 18 patients [mean age 52.4 (SD 4.8) years, left ventricular ejection function (LVEF) 27 (SD 6)%] were prospectively randomized to either 6 months of training or sedentary lifestyle. METHODS: Serum levels of growth hormone (GH) were measured by immunofluorometric assay, IGF-I by competitive solid phase immunoassay. IGF-I expression was assessed in vastus lateralis biopsies by real-time PCR. RESULTS: Exercise training led to a significant increase in peak oxygen uptake by 26% [from 20.3 (SD 3.3) ml/kg per min to 25.5 (SD 5.7) ml/kg per min, P=0.003 versus control]. Local expression of IGF-I increased significantly after exercise training by 81% [from 6.3 (SE 0.8) to 11.4 (SE 1.4) relative units, P=0.007 versus control] while IGF-I receptor expression was reduced by 33% [from 20.0 (SE 2.1) to 13.8 (SE 1.7) relative units, P=0.008 versus control]. Serum growth hormone (GH) rose modestly from 0.12 (SE 0.07) to 0.65 (SE 0.37) ng/ml in the training group (P=0.043 versus baseline), however, this change was not significant compared to the control group (P=0.848). IGF-I serum levels remained virtually unchanged. CONCLUSIONS: Exercise training improves local IGF-I expression without significant changes of systemic parameters of the GH/IGF-I axis. These findings indicate that exercise training has the therapeutic potential to attenuate peripheral skeletal muscle alterations in particular with respect to local IGF-I expression in patients with moderate CHF.

Adult↗
PubMed2005

Exercise training in chronic heart failure: correlation between reduced local inflammation and improved oxidative capacity in the skeletal muscle.

BACKGROUND: Chronic heart failure (CHF) is accompanied by an inflammatory activation which occurs both systemically and in the skeletal muscle. Exercise training has been shown to reduce the local expression of cytokines and inducible nitric oxide synthase (iNOS) in muscle biopsies of CHF patients. INOS-derived NO can inhibit oxidative phosphorylation and contribute to skeletal muscle dysfunction in CHF. DESIGN: To investigate the correlation between changes in local iNOS expression associated with regular exercise and changes in aerobic enzyme activities in the skeletal muscle of patients with CHF. Twenty male CHF patients [ejection fraction 25% (SE 2), age 54 (SE 2) years] were randomized to a training (n=10) or a control group (C, n=10). METHODS: At baseline and after 6 months skeletal muscle iNOS expression was measured by real-time polymerase chain reaction. INOS protein and protein nitrosylation were assessed by immunohistochemistry. Cytochrome c oxidase (COX) activity was quantified electrochemically using the Clark oxygen electrode. RESULTS: Exercise training led to a 27% increase in cytochrome c oxidase activity [from 21.8 (SE 3.2) to 27.7 (SE 3.5) nmol O2/mg per min, P=0.02 versus baseline]. Changes in iNOS expression and iNOS protein content were inversely correlated with changes in COX-activity (r=-0.60, P=0.01; r=-0.71, P<0.001). CONCLUSIONS: The inverse correlation between iNOS expression/iNOS protein content and COX-activity indicates that local anti-inflammatory effects may contribute to improved muscular oxidative metabolism.

Aged↗
PubMed2004

Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease: a randomized trial.

BACKGROUND: Regular exercise in patients with stable coronary artery disease has been shown to improve myocardial perfusion and to retard disease progression. We therefore conducted a randomized study to compare the effects of exercise training versus standard percutaneous coronary intervention (PCI) with stenting on clinical symptoms, angina-free exercise capacity, myocardial perfusion, cost-effectiveness, and frequency of a combined clinical end point (death of cardiac cause, stroke, CABG, angioplasty, acute myocardial infarction, and worsening angina with objective evidence resulting in hospitalization). METHODS AND RESULTS: A total of 101 male patients aged < or =70 years were recruited after routine coronary angiography and randomized to 12 months of exercise training (20 minutes of bicycle ergometry per day) or to PCI. Cost efficiency was calculated as the average expense (in US dollars) needed to improve the Canadian Cardiovascular Society class by 1 class. Exercise training was associated with a higher event-free survival (88% versus 70% in the PCI group, P=0.023) and increased maximal oxygen uptake (+16%, from 22.7+/-0.7 to 26.2+/-0.8 mL O2/kg, P<0.001 versus baseline, P<0.001 versus PCI group after 12 months). To gain 1 Canadian Cardiovascular Society class, 6956 dollars was spent in the PCI group versus 3429 dollars in the training group (P<0.001). CONCLUSIONS: Compared with PCI, a 12-month program of regular physical exercise in selected patients with stable coronary artery disease resulted in superior event-free survival and exercise capacity at lower costs, notably owing to reduced rehospitalizations and repeat revascularizations.

Aged↗
PubMed2004

Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia.

OBJECTIVE: The concept of neovascularization in response to tissue ischemia has been extended by the finding of postnatal vasculogenesis initiated by endothelial progenitor cells (EPCs). The aim of this study was to analyze whether a maximal stress test in patients with coronary artery disease (CAD) increases the number of circulating EPCs. METHODS AND RESULTS: Blood concentration of EPCs was analyzed by FACS and cell culture assay in CAD patients with (n=16) or without (n=12) exercise-induced myocardial ischemia and in healthy subjects (n=11) for up to 144 hours after maximal stress test. Plasma concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, tumor necrosis factor-alpha, and granulocyte macrophage-colony stimulating factor were determined by ELISA. EPCs increased significantly in ischemic patients, with a maximum after 24 to 48 hours (cell culture: 3.3+/-0.5-fold increase; FACS: 3.1+/-0.6-fold increase) and returned to baseline within 72 hour. In nonischemic patients and healthy subjects, no EPC increase was detectable. VEGF levels in ischemic patients increased significantly after 2 to 6 hours (maximum after 2 hours; 4.0+/-1.1-fold increase) and no change was observed in nonischemic patients and healthy subjects; DeltaVEGF and DeltaEPC correlated significantly (r=0.66). CONCLUSIONS: Patients with symptomatic CAD respond to a single episode of exercise-induced myocardial ischemia with a time-dependent increase in circulating EPCs. This increase may be related to and preceded by an increase in plasma VEGF.

Aged↗