Luke D Tapp

University of Murcia, Murcia, Murcia, Spain

Are you Luke D Tapp?

Claim your profile

Publications (19)112.33 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims The multiple roles of monocytes in atherogenesis, including inflammation, angiogenesis and repair are attributed to the existence of different monocyte sub-populations. Scarce data are available on changes in phenotype and functional status of human monocyte subsets in patients with coronary artery disease (CAD), especially when monocytes are evaluated as three distinct subsets. Methods and results Surface expression of receptors implicated in inflammation, repair and activation status (intracellular IKKβ) of monocyte subsets was assessed by flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched healthy controls. Monocyte subsets were defined as CD14++CD16−CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2− (Mon3). Plasma levels of inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p = 0.02) and Mon3 (p = 0.036), higher expression of IL6 receptor on Mon1 (p = 0.025) and Mon2 (p = 0.015), CXCR4 on Mon1 (p = 0.035) and Mon3 (p = 0.003), and CD34 on all subsets (all p < 0.007). Monocyte CD163 expression correlated negatively with interleukin (IL)-6 levels (p < 0.01 for all subsets). Expression of vascular endothelial growth factor receptor-1 correlated positively with plasminogen activator inhibitor (PAI)-1 antigen levels (r = 0.47, p = 0.006). In vitro, monocyte subsets derived from CAD patients showed significantly altered responses to endotoxin stimulation compared to monocytes from healthy controls. Conclusions There is a complex interplay between phenotype and activity of monocytes and plasma cytokines and fibrinolytic factors. These findings support the presence of unique roles for the three human monocyte subsets in atherogenesis and CAD pathogenesis.
    Atherosclerosis 01/2014; 234(1):4–10. · 3.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to evaluate the expression of cell adhesion molecule (CAM) receptors (integrins) on monocyte subsets in heart failure (HF) and examine their prognostic implication.Increased levels of soluble CAMs have been observed in patients with HF, but the precise mechanism of monocyte adhesion to the vascular endothelium remains unknown. Patients with acute HF (AHF, n=51) were compared to those with stable HF (SHF, n=42) and stable coronary artery disease (CAD, n=44) without HF. Expression of integrins-receptors to intercellular adhesion molecule-1 (ICAM-1R) and vascular CAM-1 (VCAM-1R) on monocyte subsets was assessed by flow cytometry. Monocyte subsets were defined as CD14++CD16-CCR2+ ('classical', Mon1), CD14++CD16+CCR2+ ('intermediate', Mon2), and CD14+CD16++CCR2- ('non-classical', Mon3). Compared to patients with SHF, those with AHF had significantly higher expression of ICAM-1R on Mon2 (p=0.01). Compared to those with stable CAD, patients with SHF had a significantly higher expression of ICAM-1R on Mon2 (p=0.025).Compared to SHF, patients with AHF had a similar expression of VCAM-1R on both Mon1 and Mon3 but significantly higher expression on Mon2 (p=0.019). There were no significant differences between SHF and CAD in monocyte expression of VCAM-1R. In multivariate Cox regression analysis, VCAM-1R expression on Mon2 was associated with adverse clinical outcome (death or rehospitalisation) in AHF [HR 1.07 (1.01-1.14), p=0.029]. In conclusion, HF is associated with increased monocyte expression of integrins-receptors to both ICAM-1 and VCAM-1, being particularly linked to Mon2 subset. Expression of VCAM-1R on Mon2 may have prognostic value in patients with AHF.
    Thrombosis and Haemostasis 06/2013; 110(1). · 5.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of individual monocyte subsets in inflammation and recovery post-myocardial infarction (MI) is insufficiently understood. It was the objective of this study to evaluate the dynamics of monocyte expression of receptors to vascular cell adhesion molecule (VCAM-1r), intercellular adhesion molecule (ICAM-1r), and interleukin-6 (IL-6r) following MI and their relation to inflammatory cytokines, fibrinolytic factors and annexin V-binding microparticles. Expression of VCAM-1r, ICAM-1r, IL-6r on CD14++CD16-(Mon1), CD14++CD16+(Mon2), CD14+CD16++(Mon3) monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (STEMI, n=50), non-STEMI (n=48) and stable coronary artery disease (n=40). In STEMI, parameters were measured on days 1, 3, 7, 30. On admission with STEMI, VCAM-1r expression was reduced on Mon1 (p=0.007), Mon2 (p=0.036), Mon3 (p=0.005), whilst in NSTEMI there was significant up-regulation of expression by Mon2 (p=0.024) and Mon3 (p=0.049). VCAM-1r on Mon1 correlated positively with plasma IL-1β levels (p=0.001). IL-6r was reduced on Mon2 in acute STEMI, with upregulation of the receptor on Mon1 and Mon2 during follow-up. IL-6r density correlated negatively with plasma levels of tissue-type plasminogen activator (p=0.0005 for Mon1, p=0.001 for Mon2 and Mon3), and positively with annexin V-binding microparticles (p=0.03 for Mon1, p=0.005 for Mon2 and p=0.005 for Mon3). There was no change in monocyte ICAM-1r expression. In conclusion, expression of IL-6r and VCAM-1r is reduced on circulating monocyte subsets involved in inflammatory responses in STEMI. This may represent a regulatory feed-back mechanism aiming to re-balance the marked inflammation which is typically present following acute MI or selective homing of monocytes with high receptor expression to damaged myocardium.
    Thrombosis and Haemostasis 05/2013; 110(2). · 5.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Recent evidence suggests that circulating microparticles (MPs) contribute to inflammation, coagulation and vascular injury. Majority of MPs have usually not been included into prior analyses due their small size and limited resolution of conventional equipment. Our aim was to assess levels of MPs of different cellular origin sized below 0.5 μm polystyrene beads, denoted as small-size microparticles (sMP), their relation to markers of cardiovascular repair and their impact on prognosis in patients with acute coronary syndromes (ACS). METHODS: In a cross-sectional study, we initially compared levels of sMP between patients with ST-segment elevation myocardial infarction (STEMI, n = 50), non-STEMI (n = 47), stable coronary artery disease (CAD, n = 40) and healthy individuals (HC, n = 40). In a separate study, the prognostic value of sMP was assessed in patients with non-STEMI (n = 160). Annexin V-binding sMP (sAMP), platelet CD42b(+) sMPs (sPMP), endothelial CD144(+) sMP (sEMP) and monocyte CD14(+) sMP (sMMP) were quantified using high resolution flow cytometry. Endothelial progenitor cells (EPCs) and monocyte expression of scavenger receptors was quantified by flow cytometry. Fibrinolytic factors were measured by ELISA. RESULTS: Counts of sAMP and sEMP were lower in STEMI after PCI (p < 0.001 and p = 0.025, respectively) but not in non-STEMI vs. CAD. sAMP was positively correlated with EPCs in non-STEMI (p < 0.001). Likewise, plasminogen activators negatively correlated with sAMP in non-STEMI and STEMI (p = 0.02 and p = 0.002, respectively). In non-STEMI patients, sEMP and sMMP were independently predictive for future admissions related to heart failure (p = 0.034 and 0.013, respectively) and sPMP for major bleedings (p = 0.002). The sAMP/EPCs ratio was higher in patients (before PCI) compared to STEMI patients. CONCLUSIONS: Small-size MPs could be potentially implicated in the modulation of the post-ACS reparative response to injury, with prognostic implications. Besides, the sAMP/EPCs ratio could reflect a change in the apoptotic/reparative potential, being a putative indicator for vascular repair.
    Atherosclerosis 01/2013; · 3.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Limited data are available on the role of monocytes in cardiac repair. In the present study, we evaluated the dynamic alterations of monocytes with reparative and angiogenic potential in patients with myocardial infarction(MI). Reparative CXCR4+ monocytes, and CD34+ and KDR+ monocytes with angiogenic potential derived from individual monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (n=50), and stable coronary artery disease (CAD, n=40). Parameters were measured on days 1, 3, 7 and 30 post MI. Monocyte subsets were defined as CD14++CD16-CCR2+ ('classical', Mon1), CD14++CD16+CCR2+ ('intermediate', Mon2), CD14+CD16++CCR2- ('non-classical', Mon3). Plasma levels of inflammatory cytokines, fibrinolytic factors and microparticles(MPs) were assessed on day 1. CXCR4+ and KDR+ monocytes were increased following MI, being more prominently associated with Mon2 (median[IQR] of CXCR4+ Mon2 60[25-126] per μl in STEMI vs. 27[21-41] per μl in stable CAD). The counts of CXCR4+ Mon2 in STMEI significantly reduced by day 30 of follow-up (27[18-47], p<0.001). Expression of the pro-reparative scavenger receptor CD163 on Mon3 was reduced in acute MI (p=0.008), and on other subsets later during the follow-up with lowest levels at day 3 post-MI (p<0.001 for Mon1, p=0.02 for Mon2). CD204 expression on Mon1 correlated with tissue type plasminogen activator levels (r=0.46, p=0.001). Interleukin(IL)6 levels correlated with counts of Mon2-derived CXCR4+ and KDR+ cells. Interleukin-1β correlated with KDR+ Mon2 counts. IL10 correlated with CXCR4+ Mon2 levels. Low count of CXCR4+ Mon2 and low CD163 expression by Mon2 were associated with higher ejection fraction six-weeks after MI. In conclusion, the Mon2 subset has the most prominent role in the observed changes in reparative monocytes in MI. The association of reparative monocytes with inflammatory/fibrinolytic markers indicates a complex interplay of these cells in the post-MI state.
    Thrombosis and Haemostasis 12/2012; 109(2). · 5.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: -Cross-talk between monocytes and platelets is reflected by the formation of monocyte-platelet aggregates (MPAs). It is not known whether MPAs are affected in heart failure (HF) and we examined differences in patients with acute HF (AHF), stable HF (SHF), stable coronary artery disease (CAD) without HF, and healthy controls (HC). METHODS AND RESULTS: -MPAs were analyzed by flow cytometry for the 3 monocyte subsets [CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3)] in patients with AHF (n=51), SHF (n=42), stable CAD (n=44) and HC (n=40). Counts of total MPA and MPAs associated with Mon1 and Mon2 were significantly higher in AHF compared to SHF, CAD and HC (p<0.001 for all). The proportion of Mon1 aggregated with platelets was increased in AHF compared to SHF (p=0.033), CAD (p<0.001) and HC (p<0.001). A higher percentage of Mon3 aggregated with platelets was also seen in AHF compared to SHF (p=0.012), and HC (p<0.001) but not compared to CAD (p=0.647). MPAs associated with Mon2 were significantly lower in patients who experienced adverse clinical outcomes of death or re-hospitalization compared to those who remained free of events (p=0.03). Mon2 count remained an independent negative predictor of combined death and re-hospitalization after adjustment for age, LVEF, creatinine and BNP [hazard ratio 0.58, 95% CI 0.34-0.98; p=0.043)]. CONCLUSIONS: -MPA formation in patients with both acute and stable HF is increased and appears to be confined to monocytes from Mon1 and Mon2 subsets. MPAs associated with Mon2 appear to be negatively predictive of a worse prognosis in AHF.
    Circulation Heart Failure 11/2012; · 6.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Monocytes play important roles in inflammation, angiogenesis and tissue repair and may contribute to the pathophysiology of heart failure (HF). OBJECTIVES: We examined differences in monocyte subset numbers and expression of cell surface markers of activation (CD14) and chemotaxis (CCR2) in patients with acute HF (AHF), stable HF (SHF), and controls and evaluated their impact on clinical outcomes. METHODS: Three monocyte subsets [CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3)] were analysed by flow cytometry in 51 patients with AHF, 42 patients with SHF, 44 patients with stable coronary artery disease and without HF (CAD) and 40 healthy controls (HC). The prognostic impact of monocyte subsets was examined in AHF. RESULTS: Patients with AHF had significantly higher Mon1 counts compared to the three control groups (P < 0·001 for all). Similarly, Mon2 levels were increased in AHF compared to SHF (P = 0·004) and CAD (P < 0·001) and increased in SHF vs. CAD (P = 0·009). There were no differences in Mon3 counts between the groups. Twenty patients (39·2%) with AHF reached the primary end-point of death or re-hospitalisation, and after adjustment for confounders, Mon2 count remained negatively associated with a combined end-point of death and re-hospitalisation [hazard ratio (per 10 cells/μL): 0·79; confidence interval: 0·66-0·94; P = 0·009]. CONCLUSIONS: Mon2 counts are increased in patients with both acute and stable HF, with enhanced expression of surface markers of activation (CD14) and chemotaxis (CCR2). This subset was also associated with an adverse prognosis in patients with AHF.
    European Journal of Clinical Investigation 11/2012; · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Monocyte toll-like receptor 4 (TLR4) has been implicated in the pathogenesis of atherosclerosis with increased levels in myocardial infarction. The aim of the present study was to assess the numbers of TLR4+ monocytes in each monocyte subset in MI, the expression of TLR4 and association with markers of monocyte activation, inflammation, myocardial damage and post-myocardial infarction (MI) cardiac contractility. METHODS: Surface expression of TLR4 and numbers of TLR4-expressing monocytes were quantified by flow cytometry of venous blood in 50 patients with ST-elevation MI (STEMI), 48 with non-STEMI (NSTEMI) and 40 with stable coronary artery disease (CAD). These parameters were measured on days 1, 3, 7 and 30 post-MI in STEMI patients. Three monocyte subsets were defined as CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3). Plasma inflammatory cytokines were assessed using cytometric bead arrays. RESULTS: There was a significant increase in counts of TLR4+ Mon1 and Mon2 in STEMI patients and TLR4+ Mon2 in NSTEMI patients compared with controls with CAD. Monocyte TLR4+ expression was similar between the groups, and was not changed during follow-up in STEMI patients. Plasma interleukin-6 (IL6) levels correlated positively with TLR4+ Mon2 count (r=0.54, P<0.001), but negatively with TLR4 expression on Mon2 (r=-0.33, P=0.021). CONCLUSION: Following treatment of acute MI, TLR4 expression by individual monocyte subsets is unchanged. An increase in TLR4+ Mon1 and Mon2 count in patients with STEMI and TLR+ Mon2 count in those with NSTEMI is due to an increase in monocyte subset count and not to changes in TLR4 expression. Monocyte counts but not TLR4 expression correlate positively with plasma IL6 levels. We suggest that TLR4 expression may not be a reliable marker of monocyte activation in MI. © 2012 The Association for the Publication of the Journal of Internal Medicine.
    Journal of Internal Medicine 11/2012; · 6.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Limited data are available on the role of innate fibrinolysis in acute coronary syndromes (ACS). In the present study we evaluated the dynamic alterations of fibrinolytic markers in patients presenting with ACS. Tissue-type-(tPA) and urokinase type-(uPA) plasminogen activators, plasminogen activator inhibitor (PAI-1) antigen and activity and thrombin activatable fibrinolysis inhibitor (TAFI) were analysed in 50 patients with ST elevation myocardial infarction (STEMI), 47 non-STEMI patients (NSTEMI), 40 patients with stable coronary artery disease (CAD) and 39 controls. The parameters were measured on day 1 and days 3, 7 and 30. Counts of monocyte subsets, monocyte-platelet aggregates and plasma inflammatory cytokines were assessed on admission. On day 1, TAFI was higher in NSTEMI vs. STEMI (p<0.001) while PAI-1 activity was higher in STEMI (p<0.001). In STEMI, uPA activity levels was low on day 1 but significantly increased on day 30 (p<0.001). TAFI levels were increased in NSTEMI on day 1 and gradually reduced by day 30 (p<0.05). In STEMI, TAFI levels peaked at day 7 (p<0.05) and dropped significantly by day 30 (p<0.05). CD14++CD16+ monocytes were independently associated with PAI-1 activity in ACS (p=0.03). Monocyte-platelet aggregates rather than platelet-free monocytes were an independent determinant of tPA, PAI-1 antigen and TAFI on a multivariate analysis (p<0.05). There are significant differences in fibrinolytic activity between patients with STEMI and NSTEMI. These changes could reflect the role of these factors in post-MI myocardial healing. Monocyte-platelet interactions are independently associated with the regulation of the fibrinolytic status in ACS.
    Thrombosis and Haemostasis 04/2012; 108(1):32-40. · 5.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Endothelial progenitor cells (EPCs) are known to be altered in heart failure (HF), but monocyte-derived EPCs in HF have not been assessed. We aimed to characterize monocyte-derived EPCs in systolic HF. We recruited 128 subjects with systolic HF: 50 South Asian (SA), 50 white, and 28 African-Caribbean (AC), for interethnic comparisons. Additionally, SAs with HF were compared with 40 SAs with coronary artery disease (CAD) without HF (disease controls [DCs]) and 40 SA healthy controls (HCs). Counts of CD34(+) and kinase domain receptor (KDR)(+) monocytes attributed to specific monocyte subsets (CD14(++) /CD16(-) [Mon1], CD14(++)/CD16(+) [Mon2], and CD14(+)/CD16(++) [Mon3]) and monocyte expression of vascular endothelial growth factor (VEGF) receptor 1 were analyzed by flow cytometry. We also enumerated CD34(+)/KDR(+) EPCs derived from mononuclear cells ('classic' EPC definition). SAs with HF had significantly reduced counts of CD34(+) monocytes, attributed to the Mon1 and Mon2 subsets. KDR(+) Mon1 counts were 4.5-fold increased in DCs as compared with HCs, but significantly reduced in HF subjects vs. DCs. VEGF receptor type 1 expression on Mon1 and Mon2 cells was significantly reduced in HF patients as compared with DCs. Also, CD34(+)/KDR(+) EPC numbers were reduced in HF subjects. Whites had significantly fewer KDR(+) Mon3 cells than ACs, but significantly more CD34(+) Mon2 cells than SAs and ACs. VEGF receptor type 1 expression by Mon1 cells was predictive for left ventricular ejection fraction after adjustment for ethnicity (β = - 0.25. P = 0.039). CD34(+) Mon2 counts correlated with measures of microvascular endothelial function, and were predictive of the future risk of hospital admission. Circulating counts of monocyte-derived EPCs are significantly altered in HF, with significant ethnic differences in the levels of monocyte-derived EPCs.
    Journal of Thrombosis and Haemostasis 04/2012; 10(7):1252-61. · 6.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Monocytes are important mediators in the pathophysiology of cardiovascular disease, but only scarce data are available on biological and methodological factors affecting their levels. Three monocyte subsets, CD14(++) CD16(-) CCR2+ (Mon1), CD14(++) CD16(+) CCR2(+) (Mon2), CD14(+) CD16(+) CCR2(-) (Mon3), and monocyte-platelet aggregates (MPAs) were analysed by flow cytometry. The effects of treadmill exercise were assessed on 12 healthy volunteers. Diurnal variation was evaluated in 16 healthy volunteers, and the effects of delayed blood processing were measured in 12 samples. Mon1 were increased when measured 15 min after exercise followed by a reduction at 1 h (P < 0·05 for both). MPAs were significantly reduced at 15 min and 1 h (P < 0·05 for both). There was significant diurnal variation in the numbers of Mon2, which were highest at 6 pm and lowest at 6 am. There were also significant diurnal variations in phagocytic activity of Mon1 and Mon2, which were highest at 12 pm and lowest at 12 am. Monocyte counts remained stable up to 2 h after venipuncture. MPAs were significantly increased at 2 h and increased further by 4 h after sampling. Monocyte subset Mon2 and monocyte phagocytic activity undergo significant diurnal variation. A single bout of exercise causes a temporal increase in monocytes and a reduction in MPAs. Monocyte subset counts should be analysed within 2 h of blood sampling, whereas measurement of MPAs and monocyte CD14 and CD16 expression should be performed within 1 h.
    European Journal of Clinical Investigation 02/2012; 42(8):832-9. · 3.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Monocytes contribute to both myocardial damage and repair by virtue of subset heterogeneity. The dynamics and functional characteristics of the three human monocyte subsets, including the unique CD14++CD16+ subset, and their contributions to monocyte platelet aggregates (MPAs) following ST-elevation myocardial infarction (STEMI) are unknown. We aimed to examine dynamic changes and relation to left ventricular ejection fraction (LVEF) of the three human monocyte subsets and their aggregates with platelets following STEMI. Three monocyte subsets, CD14++CD16-CCR2+ ('classical', Mon1), CD14++CD16+CCR2+ ('intermediate', Mon2) and CD14+CD16++CCR2- ('non-classical', Mon3), and their contribution to MPAs were analyzed by flow cytometry in 50 patients with STEMI, 40 patients with stable coronary artery disease (CAD) and 40 healthy volunteers. Study parameters were measured within 24 h of primary percutaneous coronary intervention (PCI) (day1) and on days 3, 7 and 30. Monocyte activation was assessed by measuring the nuclear factor κB (NFκB) pathway. LVEF was assessed 6 weeks after STEMI. Correlations between monocyte subsets/MPAs and plasma cytokines and troponin were assessed. We observed marked differences in subset dynamics, with a prominent increase in Mon2 (P < 0.0001) but no changes in Mon3. Significant increases in Mon2 CD14 (P = 0.002) and CCR2 (P < 0.0001) expression, and reduction in CD16 expression (P = 0.001) were seen. NFκB pathway activity increased most prominently in Mon2 (P = 0.007). Mon2 count correlated with peak troponin (r = 0.31, P = 0.04) and plasma interleukin (IL)-6 (r = 0.65, P < 0.0001) and IL-10 (r = 0.34, P = 0.017). Mon1 correlated with IL-6 (r = 0.55, P < 0.0001). Reduced Mon2 expression of CD16 on day 1 was independently predictive of higher LVEF (β = -0.37, P = 0.013). The increase in MPA count following STEMI persisted at 1 month. The Mon2 'intermediate' subset has unique dynamic and functional characteristics following STEMI and significant correlations with troponin, plasma cytokines and convalescent left ventricular function. The persistent increase in MPA count 30 days after STEMI may affect monocyte subset functional activity.
    Journal of Thrombosis and Haemostasis 12/2011; 10(7):1231-41. · 6.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Endothelial dysfunction is implicated in the pathophysiological features of heart failure (HF), and ethnic differences in the presentation of cardiovascular disease are evident, with an excess seen among South Asians (SAs). However, data on ethnic differences in endothelial function in HF are limited. In a cross-sectional study, we recruited 128 subjects with systolic HF: 50 SAs, 50 whites, and 28 African Caribbeans (ACs). In addition, SAs with systolic HF were compared with 40 SAs with coronary artery disease without HF ("disease controls") and 40 SA healthy controls. Macrovascular endothelial function was assessed by measurement of flow-mediated dilation (FMD) in response to hyperemia, arterial stiffness was assessed by the pulse-wave velocity, and microvascular endothelial function was assessed by forearm laser Doppler flowmetry. CD144-expressing endothelial microparticles were measured by flow cytometry. When compared with disease controls and healthy controls, SAs with HF had an impaired microvascular response to acetylcholine (P=0.001) and reduced FMD (P<0.001). In comparing ethnic groups, SAs with HF had an impaired response to acetylcholine (123±95.5%) compared with whites (258±156%) and ACs (286±173%, P<0.001 for both). Whites had a higher FMD (8.49±4.63%) than SAs (4.76±4.78%, P<0.001) and ACs (4.55±3.56%, P=0.01). No difference in endothelial-independent response was observed between study groups or in pulse-wave velocity. Ethnicity remained associated with microvascular endothelial function even after adjustment for age, presence of hypertension and diabetes mellitus, blood pressure, and glucose levels (P=0.003). There were no differences in numbers of endothelial microparticles. The SAs with HF have impaired microvascular and macrovascular endothelial function but preserved arterial elastic properties. Significant ethnic differences in endothelial function are evident in subjects with HF, with ethnicity being associated with microvascular endothelial dysfunction in this disorder.
    Circulation Heart Failure 09/2011; 4(6):754-62. · 6.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Monocytes include several subsets with different and sometimes divergent roles in immunity, atherogenesis and reparative processes. We aimed to perform detailed immunophenotypic and functional characterization of human monocyte subsets. Analysis of surface markers of blood and bone marrow monocyte subsets and functional characterization of blood monocyte subsets in healthy volunteers was performed using flow cytometry. In the present study, we show the presence of three subsets which could be unequivocally distinguished by surface expression of CD14, CD16 and CCR2 as CD14(+)CD16(-)CCR2(+) (Mon1), CD14(+)CD16(+)CCR2(+) (Mon2) and CD14(low)CD16(+)CCR2(-) (Mon3) subsets. In comparison with the classic Mon1, the Mon2 subset had the highest expression of Tie2, CXCR4, CD163, CD115, receptors to inter-cellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and the highest surface levels of apolipoprotein B and ferritin. In contrast, Mon3 had maximal expression of VCAM-1 receptors and CD204. The Mon2 and Mon3 subsets had significantly lower activity of the NFκB pathway than Mon1. Mon1 and Mon2 had similar phagocytic activity, which was significantly higher compared with Mon3. All three subsets were present in bone marrow, although the relative proportion of Mon2 in bone marrow was about 2.5-fold higher compared with that seen in blood. Significant differences in cytokine production in response to endotoxin stimulation were observed between the three monocyte subsets. Given their immunophenotypic similarity, the newly characterized Mon2 population may represent the previously reported pluripotent progenitor/pro-angiogenic monocytes.
    Journal of Thrombosis and Haemostasis 02/2011; 9(5):1056-66. · 6.08 Impact Factor
  • Source
    Chest 02/2011; 139(2):240-2. · 5.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary inter vention/stenting cannot be done according to a regimented common protocol, and stroke and bleeding risk stratification schema should be employed to individualize treatment options. A delicate balance is needed between the prevention of thromboembolism, against recurrent cardiac ischemia or stent thrombosis, and bleeding risk. New guidance from a consensus document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association and the European Association of Percutaneous Cardiovascular Interventions on the management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention/Stenting has sought to clarify some of the major issues and problems surrounding this practice, and will allow clinicians to make much more informed decisions when faced with treating such patients.
    Polskie archiwum medycyny wewnȩtrznej 07/2010; 120(7-8):290-3. · 2.05 Impact Factor
  • Circulation 03/2010; 121(10):1169-71. · 15.20 Impact Factor
  • The American journal of cardiology 02/2010; 105(4):577-8. · 3.58 Impact Factor
  • Nature Reviews Cardiology 10/2009; 6(10):619-20. · 10.40 Impact Factor

Publication Stats

89 Citations
112.33 Total Impact Points


  • 2013
    • University of Murcia
      Murcia, Murcia, Spain
  • 2011–2013
    • University of Birmingham
      Birmingham, England, United Kingdom
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2012
    • Birmingham City University
      Birmingham, England, United Kingdom
  • 2011–2012
    • University Hospitals Birmingham NHS Foundation Trust
      • Department of Medicine
      Birmingham, England, United Kingdom