***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background —In stable coronary artery disease ( CAD ) , exercise training has well-documented positive effects on arterial endothelial function . NO derived from endothelial NO synthase ( eNOS ) is regarded as a protective factor against atherosclerosis . The aim of the present study was to investigate the effects of exercise training on the endothelial function in relation to the expression of eNOS and Akt-dependent eNOS phosphorylation in the left internal mammary artery ( LIMA ) of patients with stable CAD . Methods and Results —In 17 training patients ( T ) and 18 control patients ( C ) , endothelium-dependent vasodilation and average peak flow velocity ( APV ) in response to  acetylcholine  were measured invasively at study beginning and after 4 weeks in the LIMA . In LIMA tissue sample d during bypass surgery , eNOS expression and content of pospho-eNOS-Ser1177 , Akt , and phospho-Akt were determined by Western blot and quantitative reverse transcriptase – polymerase chain reaction . After exercise training , LIMA APV in response to acetylcholine was increased by 56±8 % ( from + 48±8 % at beginning to + 104±11 % after 4 weeks , P < 0.001 ) . Patients in T had a 2-fold higher eNOS protein expression ( T 1.0±0.7 versus C 0.5±0.3 arbitrary units , P < 0.05 ) and 4-fold higher eNOS Ser1177-phosphorylation levels in LIMA-endothelium ( 1.2±0.9 versus 0.3±0.2 arbitrary units , P < 0.01 ) . A linear correlation was confirmed between Akt phosphorylation and phospho-eNOS levels ( R = 0.80 , P < 0.05 ) and between phospho-eNOS and & Dgr ; APV ( R = 0.59 , P < 0.05 ) . Conclusions —Exercise training in stable CAD leads to an improved agonist-mediated endothelium-dependent vasodilatory capacity . The change in acetylcholine-induced vasodilatation was closely related to a shear stress – induced/Akt-dependent phosphorylation of eNOS on Ser1177 Objective — Endothelial progenitor cells ( EPCs ) that may repair vascular injury are reduced in patients with coronary artery disease ( CAD ) . We reasoned that EPC number and function may be increased by granulocyte colony-stimulating factor ( G-CSF ) used to mobilize hematopoietic progenitor cells in healthy donors . Methods and Results — Sixteen CAD patients had reduced CD34+/CD133 + ( 0.0224±0.0063 % versus 0.121±0.038 % mononuclear cells [ MNCs ] , P<0.01 ) and CD133+/VEGFR-2 + cells , consistent with EPC phenotype ( 0.00033±0.00015 % versus 0.0017±0.0006 % MNCs , P<0.01 ) , compared with 7 healthy controls . Patients also had fewer clusters of cells in culture , with out-growth consistent with mature endothelial phenotype ( 2±1/well ) compared with 16 healthy subjects at high risk ( 13±4/well , P<0.05 ) or 14 at low risk ( 22±3/well , P<0.001 ) for CAD . G-CSF 10 & mgr;g/kg per day for 5 days increased CD34+/CD133 + cells from 0.5±0.2/&mgr;L to 59.5±10.6/&mgr;L and CD133+/ VEGFR-2 + cells from 0.007±0.004/&mgr;L to 1.9±0.6/&mgr;L ( both P<0.001 ) . Also increased were CD133 + cells that coexpressed the homing receptor CXCR4 ( 30.4±8.3/&mgr;L , P<0.05 ) . Endothelial cell-forming clusters in 10 patients increased to 27±9/well after treatment ( P<0.05 ) , with a decline to 9±4/well at 2 weeks ( P=0.06 ) . Conclusions — Despite reduced EPCs compared with healthy controls , patients with CAD respond to G-CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out-growth in culture Abstract Habitual exercise provides repeated episodes of elevated vascular shear stress ( SS ) , which may be a mechanism for repair of endothelial dysfunction in disease . Our aim was to determine the brachial artery SS during the 3–hour period following single bouts of low , moderate , and high-intensity walking exercise . In a r and omized crossover design , 14 men walked for 45 minutes on a treadmill  at 25 % , 50 % and 75 % of VO2peak separated by 2–7 days . Using Doppler ultrasonography , brachial artery SS was assessed immediately after exercise and then hourly for 3 hours . High-intensity walking elicited greater ( p < 0.05 ) post-exercise SS compared with low and moderate intensity . In addition , a 3 x 4 ( intensity x time ) ANOVA indicated an absence of interaction ( p = 0.369 ) and a decline in post-exercise SS over time ( p < 0.0001 ) which was abolished after 2 hours . Thus , we found that brachial artery SS is greatest following high-intensity walking and that the rate of decline in SS is similar across all walking intensities BACKGROUND The molecular mechanisms by which physical training improves peripheral and coronary artery disease are poorly understood . Bone marrow-derived endothelial progenitor cells ( EPCs ) are thought to exert beneficial effects on atherosclerosis , angiogenesis , and vascular repair . METHODS AND RESULTS To study the effect of physical activity on the bone marrow , EPCs were quantified by fluorescence-activated cell sorter analysis in mice r and omized to running wheels ( 5.1+/-0.8 km/d , n=12 to 16 per group ) or no running wheel .  Numbers of EPCs circulating in the peripheral blood of trained mice were enhanced to 267+/-19 % , 289+/-22 % , and 280+/-25 % of control levels after 7 , 14 , and 28 days , respectively , accompanied by a similar increase of EPCs in the bone marrow and EPCs exp and ed from spleen-derived mononuclear cells . eNOS-/- mice and wild-type mice treated with N(G)-nitro-l-arginine methyl ester showed lower EPC numbers at baseline and a significantly attenuated increase of EPC in response to physical activity . Exercise NO dependently increased serum levels of vascular endothelial growth factor and reduced the rate of apoptosis in spleen-derived EPCs . Running inhibited neointima formation after carotid artery injury by 22+/-2 % . Neoangiogenesis , as assessed in a subcutaneous disc model , was increased by 41+/-16 % compared with controls . In patients with stable coronary artery disease ( n=19 ) , moderate exercise training for 28 days led to a significant increase in circulating EPCs and reduced EPC apoptosis . CONCLUSIONS Physical activity increases the production and circulating numbers of EPCs via a partially NO-dependent , antiapoptotic effect that could potentially underlie exercise-related beneficial effects on cardiovascular diseases 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 r and omized to 4 weeks of daily ischemic ET or control ( group A ) . Successfully revascularized patients with PAOD were r and omized 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 1 . The present study investigates to what extent and by which time course prolonged strenuous exercise influences the plasma concentration of pro-inflammatory and inflammation responsive cytokines as well as cytokine inhibitors and anti-inflammatory cytokines . 2 . Ten male subjects ( median age 27.5 years , range 24 - 37 ) completed the Copenhagen Marathon 1997 ( median running time 3 : 26 ( h : min ) , range 2 : 40 - 4 : 20 ) . Blood sample s were obtained before , immediately after and then every 30 min in a 4 h post-exercise recovery period . 3 . The plasma concentrations of tumour necrosis factor (TNF)alpha , interleukin (IL)-1beta , IL-6 , IL-1ra , sTNF-r1 , sTNF-r2 and IL-10 were measured by enzyme-linked immunosorbent assay ( ELISA ) . The highest concentration of IL-6 was found immediately after the race , whereas IL-1ra peaked 1 h post exercise ( 128-fold and 39-fold increase , respectively , as compared with the pre-exercise values ) . The plasma level of IL-1beta , TNFalpha , sTNF-r1 and sTNF-r2 peaked in the first hour after the exercise ( 2 . 1- , 2.3- , 2.7- and 1.6-fold , respectively ) . The plasma level of IL-10 showed a 27-fold increase immediately post exercise . 4 . In conclusion , strenuous exercise induces an increase in the pro-inflammatory cytokines TNFalpha and IL-1beta and a dramatic increase in the inflammation responsive cytokine IL-6 . This is balanced by the release of cytokine inhibitors ( IL-1ra , sTNF-r1 and sTNF-r2 ) and the anti-inflammatory cytokine IL-10 . The study suggests that cytokine inhibitors and anti-inflammatory cytokines restrict the magnitude and duration of the inflammatory response to exercise Endothelial progenitor cells ( EPCs ) and late outgrowth endothelial cells ( OECs ) seem to play an important role in vessel formation . While EPCs seem to exert their function mainly through a paracrine effect , the OECs can develop into mature endothelial cells and form tubular structures . Exercise is known to increase angiogenic factors that can mobilize EPCs ; however , the effect on OECs is not known . We investigated the response to a single session of strenuous exercise on OECs , vascular endothelial growth factor ( VEGF ) and inflammatory cell levels in the healthy . Eleven healthy subjects performed 1 h of spinning exercise .  Blood sample s were collected at 1 , 6 , 24 and 48 h post-exercise for cell culture and biochemical analysis . OEC colonies doubled one hour after the spinning session ( baseline 4.5 ± 4.3 vs. 9.0 ± 3.7 , P < 0.05 ) . Serum VEGF increased from 194 ± 107 pg/ml at baseline to 224 ± 111 pg/ml after 1 h , p = ns and neutrophilic granulocytes increased from 3.73 ± 1.38 at baseline to 9.08 ± 10.5 at 1 h ( P < 0.01 ) . The increased levels of OECs , VEGF and neutrophilic granulocytes declined gradually at the following time points . VEGF levels and neutrophilic granulocytes were highly correlated to OEC levels , r = 0.903 ( VEGF ) and r = 0.85 ( neutrophilic granulocytes ) , respectively . Strenuous physical activity increases OEC colonies and is correlated to serum VEGF and neutrophilic granulocytes levels . An acute exercise-induced inflammatory response might be responsible for the VEGF release and subsequent increase of OECs . The clinical importance of these findings 
    Output:
    
The magnitude and duration of the EPC mobilization response were higher after long/ultralong duration exercises , and they are correlated with vascular endothelial growth factor ( VEGF ) plasma levels .
The EPC mobilization peak in response to a maximal or submaximal single bout of exercise lasting up to one hour occurs immediately after the exercise or within the first hour after it .
One possible mechanism is nitric oxide ( NO ) bioavailability .
The individuals ' age and exercise intensity seem to interfere with the EPC mobilization response .
Long/ultralong duration exercises promote more pronounced EPC mobilization as compared with maximal or submaximal exercises .
The mechanisms involve VEGF release in long/ultralong duration exercises and NO bioavailability in maximal or submaximal exercises lasting less than one hour