Biomedical subjects

Markus Exner

Publications and source records attributed to Markus Exner.

At least 55 records · Page 3Linked to original sources

PubMed2004

The effect of a promoter polymorphism in the heme oxygenase-1 gene on the risk of ischaemic cerebrovascular events: the influence of other vascular risk factors.

Heme oxygenase-1 (HO-1) has been demonstrated to exert potent anti-oxidant and anti-inflammatory effects in the context of atherosclerotic vascular disease, and therefore was referred to as a potential vascular protective factor. A (GT)n dinucleotide repeat polymorphism in the HO-1 promoter has been shown to modulate HO-1 gene expression. Short (<25) GT repeats were associated with HO-1 up-regulation, and therefore may influence susceptibility to ischaemic vascular events. We investigated the association of HO-1 repeat length with the risk of cerebrovascular events in a case control study and assessed possible interrelations with vascular risk factors. We determined the number of GT repeats in the HO-1 promoter in 399 patients with ischaemic cerebrovascular events and 398 healthy controls and compared the frequencies of short (<25) repeat (class S) and long (> or =25) repeat (class L) alleles after adjustment for potentially confounding factors. Genotype distributions of S/S, S/L and L/L in patients were 9.8% (n=39), 45.1% (n=180) and 45.1% (n=180), which was similar to the distribution in controls with 11.5% (n=46), 44.5% (n=177) and 44.0% (n=175). In the presence of vascular risk factors, the HO-1 genotype became functionally relevant: in patients without hyperlipidemia the S/S genotype exerted a protective effect on the development of ischaemic cerebrovascular events (OR 0.2; 95% CI 0.1-0.6), while this effect was no longer present in hyperlipidemic patients. Short (<25 GT) repeats in the HO-1 gene promoter confer a reduced risk for cerebrovascular events in individuals with normal plasma lipid levels. This may explain controversial findings in different populations.

Adult↗

PubMed2004

Endovascular brachytherapy: effect on acute inflammatory response after percutaneous femoropopliteal arterial interventions.

PURPOSE: To investigate whether endovascular brachytherapy diminishes vascular inflammation in response to femoropopliteal percutaneous transluminal angioplasty (PTA) or stent implantation in two double-blind randomized-controlled trials. MATERIALS AND METHODS: Forty-seven consecutive patients from two double-blind randomized-controlled trials were studied. Patients either underwent femoropopliteal PTA with endovascular gamma irradiation (n = 8) or placebo irradiation (n = 7) or underwent PTA and stent implantation with brachytherapy (n = 15) or placebo irradiation (n = 17). High-sensitivity C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen levels were measured at baseline and 8, 24, and 48 hours after the intervention. The change of acute phase parameters from baseline to 48 hours after intervention indicated the extent of the inflammatory response and was compared between patients undergoing brachytherapy and those undergoing placebo irradiation. Fisher exact test was used for comparison of categorical data, and nonparametric statistical methods were applied for analysis of continuous data (Mann-Whitney U tests for unpaired data and Friedman analysis for repetitive measurements). RESULTS: Median patient age was 70 years (interquartile range, 56-74 years); 33 (70%) patients were men and 14 (30%) were women. Clinical characteristics and baseline values of acute phase parameters were similar between groups. A statistically significant increase in CRP, SAA, and fibrinogen values was observed after PTA and stent implantation, both in the patients who underwent brachytherapy and in those who underwent placebo irradiation. Compared with placebo irradiation, however, brachytherapy did not significantly reduce any acute phase parameter from baseline to 8, 24, or 48 hours after the intervention (P >.05 for all comparisons). CONCLUSION: Endovascular brachytherapy did not diminish early vascular inflammation in response to PTA or stent implantation and even induced a trend toward an increased inflammatory response.

Acute-Phase Reaction↗

PubMed2004

Effect of smoking on restenosis during the 1st year after lower-limb endovascular interventions.

PURPOSE: To investigate whether smoking has an effect on recurrent lumen narrowing after percutaneous transluminal angioplasty (PTA) or stent placement in lower-limb arteries. MATERIALS AND METHODS: A total of 650 patients (median age, 70 years; 389 men) with peripheral artery disease who underwent iliac artery PTA (n = 95), iliac artery stent placement (n = 83), femoropopliteal PTA (n = 406), or femoropopliteal stent placement (n = 66) were selected from a prospective database. Patients were categorized according to their preintervention smoking habits as nonsmokers (n = 352), light smokers (one to nine cigarettes daily) (n = 54), habitual smokers (10-20 cigarettes daily) (n = 82), or heavy smokers (>20 cigarettes daily) (n = 162). Multivariate Cox proportional hazards analysis was used to determine whether there was an association between smoking habits and restenosis (> or =50%) in the treated vessel segment within 1 year after treatment. RESULTS: Cumulative restenosis rates at 6 and 12 months according to patients' smoking habits were 99 and 190 nonsmokers, 18 and 22 light smokers, 16 and 29 habitual smokers, and 26 and 47 heavy smokers, respectively (P <.001). Adjusted hazard ratios for restenosis in smokers compared with nonsmokers were 1.51 (95% CI: 0.92, 2.50) for light smokers, 0.49 (95% CI: 0.28, 0.87) for habitual smokers, and 0.46 (95% CI: 0.30, 0.71) for heavy smokers, indicating a reduced restenosis risk in patients who smoked 10 or more cigarettes daily. These patients had reduced restenosis rates after either iliac (P =.011) or femoropopliteal intervention (P =.009). However, endovascular treatment at a younger age, coronary artery disease, and history of myocardial or cerebrovascular infarction were more frequently found in smokers. CONCLUSION: Smoking 10 or more cigarettes daily is associated with a reduced rate of intermediate-term restenosis after lower-limb endovascular interventions.

Aged↗

PubMed2004

A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with increased bilirubin and HDL levels but not with coronary artery disease.

Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous anti-oxidant bilirubin which exerts beneficial effects against arteriosclerosis. A (GT) repeat polymorphism in the HO-1 promoter region modulates HO-1 expression in response to oxidative stress. Recently, this polymorphism has been reported to protect from coronary artery disease in Orientals. We intended to confirm this observation in Caucasians. We studied 649 individuals with myocardial infarction (n=258), stable coronary artery disease (n=180) and controls without coronary artery disease (n=211). Carriers of short alleles (<25 repeats) had higher bilirubin levels (median 0.66 mg/dL, IQR 0.49 to 0.91) compared to non-carriers (median 0.61 mg/dL, IQR 0.45 to 0.82; p=0.03) and a more favourable lipid profile (HDL median 47 mg/dL, IQR 40 to 50 vs. median 45, IQR 37 to 55, p=0.01; triglycerides median 118 mg/dL, IQR 87 to 174 vs. median 132, IQR 97 to 191, p=0.03). However, no significant differences of the genotype distribution were observed between the three groups in this Caucasian study population (p=0.94). Although potentially beneficial effects of the short HO-1 allele on lipid profile and serum bilirubin were observed, in contrast to Orientals, the HO-1 genotype was not associated with coronary artery disease in Caucasians.

Adult↗

PubMed2004

E-Selectin and restenosis after femoropopliteal angioplasty: prognostic impact of the Ser128Arg genotype and plasma levels.

Perivascular inflammation plays a key role in the development of restenosis after percutaneous transluminal angioplasty (PTA). The adherence of leucocytes to the activated endothelium, an essential feature in the restenotic process, is mediated by the cellular adhesion molecule E-Selectin. A DNA polymorphism in the regulator region of E-Selectin at codon 561 (Ser128Arg) is suggested to modulate the molecule's physiological effects. Therefore, we investigated the association between the E-Selectin Ser128Arg genotype, E-Selectin plasma levels and restenosis after femoropopliteal PTA. We prospectively studied 175 consecutive patients with peripheral artery disease and intermittent claudication (n=126) or critical limb ischemia (n=49) who underwent primary successful femoropopliteal balloon angioplasty. E-Selectin Ser128Arg genotype and base-line E-Selectin plasma levels were determined and patients were followed up for median 12 months (IQR 11 to 14, total range 6 to 24) for the occurrence of postangioplasty restenosis(>/=50%). E-Selectin plasma levels in homozygous Arg128Arg and heterozygous Ser128Arg patients were significantly higher compared to wildtype Ser128Ser patients (p=0.041). Patency rates for wildtype Ser128Ser, heterozygous Ser128Arg and homozygous Ser128Ser patients were 57%, 44% and 50% at 6 months, and 46%, 40% and 17%, at 12 months, respectively (Log Rank p=0.31). Patency rates for increasing tertiles of E-Selectin were 61%, 58% and 37% at 6 months, and 54%, 45% and 30% at 12 months, respectively (Log Rank p=0.020). Patients with an E-Selectin plasma level above 44.9 mg/dL (third tertile) had an 1.9-fold increased adjusted risk for restenosis (95% CI 1.09 to 3.30). E-Selectin plasma levels are modulated by the E-Selectin Ser128Arg genotype, and predict the risk for restenosis after PTA in patients with PAD. A direct association of the Ser128Arg polymorphism with late postangioplasty failure could not be demonstrated.

Aged↗

PubMed2004

Serum albumin predicts cardiac adverse events in patients with advanced atherosclerosis - interrelation with traditional cardiovascular risk factors.

Low serum albumin is a powerful predictor of cardiovascular adverse events in healthy subjects and patients with subclinical, atherosclerosis. We investigated the association between serum albumin, traditional cardiovascular risk factors, markers of inflammation and cardiovascular outcome in 515 patients with advanced atherosclerosis and severe peripheral artery disease. Cardiovascular risk profile, serum albumin, serum amyloid A (SAA) and fibrinogen were obtained at baseline, and patients were followed for median 21 months (interquartile range 12 to 25) for the occurrence of major adverse cardiac events (MACE: myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, and death). We observed 135 MACE in 109 patients (21%). Cumulative event-free survival rates at 6, 12, and 24 months were 95%, 91%, and 80%, respectively. Low albumin predicted MACE independently of SAA and fibrinogen. Adjusted hazard ratios for the occurrence of MACE, any death, and the composite of death and MI according to increasing quartiles of albumin were 2.40, 1.14 and 1.09 (p<0.001), 2.94, 1.34 and 1.11 (p=0.003) and 3.63, 1.86 and 1.29 (p<0.001), respectively, as compared to the highest quartile. Considering albumin in conjunction with traditional cardiovascular risk factors (smoking, hyperlipidemia, hypertension and diabetes), we found that low albumin predicted MACE only in patients with a low risk profile (less than 3 risk factors) (p<0.001), whereas low albumin was not associated with MACE in patients with three or more risk factors (p=0.66). We conclude that low serum albumin is associated with cardiovascular outcome of patients with advanced atherosclerosis adding to the prognostic information of other inflammatory markers, and may be particularly useful for risk prediction in patients with few traditional risk factors.

Aged↗

PubMed2004

High plasma heparin cofactor II activity protects from restenosis after femoropopliteal stenting.

High heparin cofactor II (HCII) activity has recently been described to protect from coronary instent restenosis, presumably by inactivating thrombin in injured arteries. In this study, we investigated the association of HCII activity and restenosis after femoropopliteal stenting. We studied 63 consecutive patients with peripheral artery disease who underwent femoropopliteal stent implantation after initial failure of plain balloon angioplasty due to a significant residual stenosis (>30% lumen diameter reduction) or a flow limiting dissection. HCII activity was measured before stenting and patients were followed for median 10 months (interquartile range 6 to 17) for the occurrence of a first instent restenosis, defined as a >50% lumen diameter reduction by color coded duplex sonography and confirmed by angiography. Cumulative freedom from restenosis at 6 and 12 months in patients with lower HCII activity (100%, lower tertile, n=20) was 84% and 35% as compared to 93% and 72% in patients with high HCII activity (>100%, middle and upper tertile, n=43; p=0.024 by Log Rank test). Adjusting for the material of the implanted stents (nitinol vs. Wallstents), patients with a high HCII activity had a 0.39-fold reduced risk for instent restenosis (95% CI 0.17 to 0.90, p=0.028), additional adjustment for diabetes mellitus, poor run-off, critical limb ischemia and cumulative length of the stented segment did not alter the observed effect. Higher activity of heparin cofactor II may exert a protective effect against instent restenosis also in the femoropopliteal vessel area, confirming a prior observation after coronary stenting.

Aged↗

PubMed2004

Excessive carotid in-stent neointimal formation predicts late cardiovascular events.

PURPOSE: To examine if excessive in-stent neointimal formation causing a subcritical stenosis may indicate enhanced vascular reactivity in response to injury, thus predicting late cardiovascular events. METHODS: One hundred consecutive patients (64 men; median age 71 years) with high-grade internal carotid artery stenoses (68 asymptomatic, 32 symptomatic) underwent carotid artery stenting (CAS). High-sensitivity C-reactive protein (hs-CRP) was measured before CAS. Patients were monitored with duplex ultrasound for excessive in-stent neointimal formation (flow-compromising lumen diameter reduction >/=50%), critical restenosis (>/=70%), or the occurrence of late major adverse cardiovascular events (MACE) defined as myocardial infarction (MI), stroke, and death occurring later than 30 days poststenting. RESULTS: Over a median 23-month follow-up, excessive neointimal formation was observed in 14 (14%) patients, restenosis in 2 (2%), and 30 late MACE in 25 [25%: 4 MIs, 2 ipsilateral strokes (in the patients with restenosis), 8 contralateral strokes, and 16 cardiovascular deaths]. Cumulative MACE-free survival rates at 6, 12, and 24 months were 92%, 84%, and 77%, respectively. Baseline hs-CRP levels were associated both with neointimal hyperplasia (p=0.024) and MACE (p=0.021). Patients with excessive neointimal formation exhibited a significantly increased adjusted risk for MACE (hazard ratio 3.56, p=0.010). CONCLUSIONS: Excessive in-stent neointimal formation after CAS indicates an increased risk for late MACE, potentially reflecting a state of exaggerated vascular reactivity in response to injury. Inflammation, which is associated both with neointimal hyperplasia and MACE, seems a common characteristic of different vascular pathologies.

Aged↗

PubMed2003

Low serum magnesium predicts neurological events in patients with advanced atherosclerosis.

BACKGROUND AND PURPOSE: Magnesium (Mg) deficiency is thought to be a risk factor for cerebrovascular atherosclerosis and complications. We investigated the prognostic impact of Mg serum levels with respect to the occurrence of neurological events in patients with advanced atherosclerosis. METHODS: We prospectively studied 323 patients with symptomatic peripheral artery disease and intermittent claudication (197 men; median age, 68 years). Serum Mg was determined, and patients were followed for a median of 20 months (interquartile range, 12 to 25 months) for the occurrence of neurological events, defined as ischemic stroke and/or carotid revascularization (carotid endarterectomy or carotid stenting). Multivariate Cox proportional hazards analysis was applied to assess the association of serum Mg (in tertiles) and neurological events. RESULTS: Neurological events occurred in 35 patients (11%) (15 patients with stroke, 13 with carotid revascularization, and 7 with stroke and subsequent revascularization). Compared with patients in the highest tertile of Mg serum levels (>0.84 mmol/L), patients with Mg serum values <0.76 mmol/L (lowest tertile) exhibited a 3.29-fold increased adjusted risk (95% CI, 1.34 to 7.90; P=0.009) for neurological events, but patients with Mg serum values of 0.76 mmol/L to 0.84 mmol/L (middle tertile) had no increased risk (adjusted hazard ratio, 1.10; 95% CI, 0.35 to 3.33; P=0.88). Mg serum levels were not associated with all-cause mortality (P=0.87) or coronary events (P=0.67) during follow-up. CONCLUSIONS: Low Mg serum levels indicate an increased risk for neurological events in patients with symptomatic peripheral artery disease, favoring Mg substitution therapy in those patients with advanced atherosclerosis.

Aged↗

PubMed2003

Joint effects of C-reactive protein and glycated hemoglobin in predicting future cardiovascular events of patients with advanced atherosclerosis.

BACKGROUND: C-reactive protein (CRP) and glycohemoglobin (HbA1c) are established risk factors for the development of cardiovascular disease. We investigated the joint effects of these parameters on cardiovascular outcome of patients with advanced atherosclerosis. METHODS AND RESULTS: We studied 454 patients with advanced atherosclerosis (median age, 69 years; 264 male). Cardiovascular risk profile, high-sensitivity CRP (hs-CRP), and HbA1c were obtained at baseline, and patients were followed for a median of 21 months (interquartile range, 13 to 26) for the occurrence of major adverse cardiovascular events (MACE) (myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, carotid revascularization, stroke, and death). We observed 166 MACE in 128 patients (28%). Cumulative event-free survival rates at 6, 12, and 24 months were 91%, 85%, and 73%, respectively. Adjusted hazard ratios for the occurrence of MACE according to increasing quartiles of hs-CRP and HbA1c were 1.35 (P=0.31), 1.90 (P=0.026) and 2.13 (P=0.007), and 1.40 (P=0.26), 1.81 (P=0.059), and 2.36 (P=0.023), respectively, compared with the lowest quartiles. Considering both parameters jointly, we found that patients with hs-CRP >0.44 mg/dL and HbA1c >6.2% (upper quartiles) were at highest risk for MACE, with each parameter adding to the prognostic information of the other. CONCLUSIONS: Inflammation, indicated by hs-CRP, and hyperglycemia, indicated by HbA1c, jointly contribute to the cardiovascular risk of patients with advanced atherosclerosis. Patients with both hs-CRP and HbA1c in the upper quartiles (>0.44 mg/dL and >6.2%, respectively) are at particularly high risk for poor cardiovascular outcome.

Aged↗

PubMed2003

When renal allografts turn DARC.

BACKGROUND: The Duffy antigen-receptor for chemokines (DARC) is a chemokine-binding protein that is up-regulated on peritubular capillaries (PTC) during cellular renal allograft rejection. C4d deposition and accumulation of inflammatory cells in PTC are indicators of humoral renal allograft rejection. Because DARC is expressed at the site of C4d deposition and might be involved in inflammatory cell recruitment, the authors evaluated the expression of DARC in different forms of human renal allograft rejection. METHODS: Deposition of C4d and DARC expression were evaluated by immunohistochemistry in 42 renal transplant biopsy specimens. Biopsy specimens were subdivided according to histologic and immunohistochemical results, that is, C4d-negative biopsy specimens with (Banff 1, n=8) or without signs of cellular rejection (n=16), and C4d-positive biopsies (humoral rejection) with (Banff 1 rejection, n=7) or without cellular rejection (n=11). RESULTS: DARC expression was found on a small number of PTC and veins in patients without rejection. Cellular and humoral rejection led to a comparable increase in the number of DARC-positive PTC (9.7 and 8.7 vs. 2.6 vessels per high-power field [HPF], respectively). The highest numbers were found in biopsy specimens with signs of both humoral and cellular rejection (17.5 vessels per HPF). CONCLUSIONS: This is the first study that demonstrates an induction of a chemokine-binding protein at the site of C4d deposition in humoral allograft rejection. The additive effect of humoral and cellular rejection on DARC expression might imply different pathways of DARC induction for different forms of allograft rejection.

Acute Disease↗

PubMed2003

Flow cytometry based detection of HLA alloantibody mediated classical complement activation.

Complement-dependent cytotoxicity (CDC) panel reactive antibody (PRA) testing is used to assess recipient presensitization and post-transplant alloantibody formation in transplant recipients. However, CDC test results can be affected by false-positive reactions brought about by autoantibodies or antilymphocyte reagents. As an alternative to the CDC-PRA assay, detection of HLA alloantibodies using HLA antigen-coated microbeads (FlowPRA test) was recently established. FlowPRA testing, however, does not distinguish between (presumably more harmful) complement-fixing and noncomplement-fixing alloantibodies. In this study, we established a novel assay allowing flow cytometric detection of HLA alloantibody dependent classical complement activation using the FlowPRA test. For the detection of complement activation, FlowPRA beads were incubated with sera from highly sensitized dialysis patients (CDC-PRA reactivity >60%) and then stained for C4 (C4d, C4c) and C3 (C3d, C3c) fragments, as well as C1q deposition using indirect immunofluorescence. We demonstrate alloantibody induced induction of C4 fragment, and in parallel C1q deposition to HLA class I or class II beads. As shown by immunoblotting, C4 staining was not due to the presence of preformed C4 fragment-IgG/M complexes. Indeed, C4 fragment deposition in our in vitro system was demonstrated to result from de novo complement activation. First, inactivation of C4 by treatment of sera with methylamine, which inhibits cleavage of the internal thioester, completely abolished C4 fragment deposition. Second, C4 fragment deposition was not observed in the evaluation of C4-free immunoadsorption eluates obtained from highly sensitized dialysis patients. After supplementation with complement, however, eluates induced C4 deposition. Deposition of C4 split products and C1q was temperature-dependent with maximum binding after incubation at 4 degrees C for 60 min. In contrast, maximum C3 fragment deposition was found at 37 degrees C. At this temperature, C3 deposition occurred in an alloantibody and C4-independent fashion, presumably as a result of alternative complement activation. In summary, we describe a novel cell-independent and easy-to-perform PRA test that permits flow cytometry based detection of alloantibody induced classical complement activation. Future studies will have to evaluate its possible relevance as an alternative to CDC-PRA testing in clinical transplantation.

Case-Control Studies↗

PubMed2003

Endovascular revascularization below the knee: 6-month results and predictive value of C-reactive protein level.

PURPOSE: To determine the association between pre- and postintervention serum C-reactive protein (CRP) levels and 6-month restenosis after endovascular treatment of atherosclerotic lesions in arteries below the knee. MATERIALS AND METHODS: Eighty-nine patients with peripheral arterial disease underwent primary successful percutaneous transluminal angioplasty (PTA) of the distal popliteal, anterior tibial, posterior tibial, and fibular arteries. Six-month patency was evaluated with the ankle brachial index (ABI) and color-coded duplex ultrasonography (US). The association between restenosis and preintervention and 48-hour postintervention CRP levels was assessed with multiple logistic regression analysis. RESULTS: ABI improved from a preintervention median of 0.54 to a postintervention median of 0.75 (P <.001). The primary technical success rate was 94% (100 of 106). In 50 patients, a suboptimal technical result was achieved with 30%-40% residual stenosis at the dilated segment. The median ABI at 6 months was 0.65, and it was inversely correlated with preintervention (r = -0.27, P =.009) and 48-hour postintervention (r = -0.40, P <.001) CRP levels. With duplex US at 6 months, restenosis (> or =50%) occurred in 36 patients. Patients with a preintervention CRP level of 0.23-0.92 mg/dL (2.3-9.2 mg/L) had a 3.7-fold increased adjusted risk for restenosis (P =.05); patients with a preintervention CRP level greater than 0.92 mg/dL (9.2 mg/L) had a 4.7-fold increased adjusted risk (P =.03). Postintervention CRP values greater than 2.42 mg/dL (24.2 mg/L) were associated with a 10.7-fold adjusted risk for restenosis (P =.002). Suboptimal PTA result was the only other parameter associated with an increased risk for restenosis (odds ratio, 3.7; P =.03). CONCLUSION: Pre- and postintervention CRP levels were associated with restenosis after PTA of the distal popliteal and tibioperoneal arteries, which indicates that inflammation plays a crucial role in the pathophysiology of this process.

Aged↗

PubMed2003

Acute-phase response after stent implantation in the carotid artery: association with 6-month in-stent restenosis.

PURPOSE: To determine the prognostic importance of periintervention serum levels of acute-phase reactants in 6-month restenosis after stent implantation in the carotid artery. MATERIALS AND METHODS: One hundred eight consecutive patients with 70% or greater stenosis of the internal carotid artery (ICA) according to the North American Symptomatic Carotid Endarterectomy Trial criteria underwent successful stent implantation in the ICA in a prospective cohort study. Six-month patency was evaluated at color-coded duplex ultrasonography. The association between in-stent restenosis (> or =50%, North American Symptomatic Carotid Endarterectomy Trial criterion) and C-reactive protein (CRP) and serum amyloid A levels at baseline and at 24 and 48 hours after intervention was assessed. RESULTS: Restenosis was found in 15 (14%) patients within 6 months. CRP level at 48 hours, exemplary for the postintervention acute-phase response, was significantly (P =.01) associated with 6-month restenosis by using multiple logistic regression analysis. Recurrent stenosis after prior stent implantation in the carotid artery (odds ratio, 9.2; 95% CI: 1.6, 53.2; P =.01) and residual stenosis of 10%-30% after stent implantation (odds ratio, 9.7; 95% CI: 1.6, 59.3; P =.01) were independent clinical predictors of restenosis. CONCLUSION: Extent of vascular inflammatory response after stent implantation in the carotid artery measured with acute-phase reactants is associated with 6-month patency. Recurrent stenosis after prior stent implantation and initial suboptimal technical result seem to be clinically relevant predictors of postangioplasty outcome.

Acute-Phase Proteins↗

PubMed2003

The E-selectin S128R polymorphism is not a risk factor for coronary artery disease in patients with diabetes mellitus type 2.

AIM/HYPOTHESIS: E-selectin is thought to play a key role in the early stages of vascular disease by facilitating the attachment of leukocytes to the endothelium. Recently, a polymorphism in the E-selectin gene (S128R) has been associated with higher E-selectin levels in patients with diabetes mellitus and with premature coronary artery disease. The impact of the S128R polymorphism on the development of diabetic coronary artery disease has not been investigated yet. PATIENTS AND METHODS: A total of 254 patients recruited from the Division of Cardiology, University of Vienna with diabetes mellitus type 2 was assessed for the E-selectin S128R polymorphism by a novel mutagenic separated PCR, allowing fast and reliable genotyping without restriction enzyme digest. Ninety-five patients had a history of myocardial infarction, 90 were admitted with stable coronary artery disease whereas in 69 the presence of CAD could be excluded. RESULTS: Of all 254 individuals tested, 197 (77.6%) exhibited wildtype E-selectin 128S genotype, 54 (21.3%) were heterozygous S128R and 3 (1.1%) were homozygous for the 128R allele. In all groups the genotype frequencies did not differ significantly. No associations were found between E-selectin genotype and coronary artery disease or myocardial infarction. CONCLUSION/INTERPRETATION: In subjects suffering from diabetes mellitus type 2 the E-selectin S128R polymorphism is not associated with coronary artery disease nor with an increased risk for myocardial infarction. Thus, screening for this polymorphism is not indicated for risk assessment of CAD in patients with diabetes mellitus.

Aged↗

PubMed2003

Free and peptide-bound DOPA can inhibit initiation of low density lipoprotein oxidation.

Hydroxyl radicals have been shown to convert free tyrosine to 3,4-dihydroxyphenyl-alanine (DOPA) which has reducing properties. During protein or peptide oxidation such reducing species are also formed from tyrosine residues. Free DOPA or peptide-bound DOPA (PB-DOPA) is able to promote radical-generating events, facilitating the damage of biomolecules such as nucleic acids. Radical induced lipid oxidation in low density lipoprotein (LDL) transforms the lipoprotein into an atherogenic particle. As PB-DOPA has been found in atherosclerotic plaques, we tested the ability of free and PB-DOPA to influence LDL oxidation. Free DOPA, in contrast to tyrosine had strong inhibitory action on both, the copper-ion initiated and metal ion independent (AAPH-induced) lipid oxidation. Free DOPA also inhibited LDL oxidation induced by the copper transport protein ceruloplasmin. To test if PB-DOPA was also able to inhibit LDL oxidation, DOPA residues were generated enzymatically in the model peptides insulin and tyr-tyr-tyr, respectively. PB-DOPA formation substantially increased the ability of both molecules to inhibit LDL oxidation by copper or AAPH. We hypothesize that DOPA-peptides and -proteins may have the potential to act as efficacious antioxidants in the atherosclerotic plaque.

Antioxidants↗

PubMed2003

Interleukin-1 cluster combined genotype and restenosis after balloon angioplasty.

The interleukin-1 system is fundamentally involved in the pathogenesis of restenosis after percutaneous transluminal angioplasty (PTA). In order to further define the clinical impact of genetic variation in this potent proinflammatory pathway we investigated the joint effects of two single nucleotide polymorphisms in the interleukin-1 beta gene [IL-1B(-511) and IL-1B(+3954)] and a variable number tandem repeat polymorphism in intron 2 of the interleukin 1 receptor antagonist gene (IL-1RN VNTR) on postintervention inflammation and occurrence of restenosis in 183 consecutive patients who underwent successful femoropopliteal PTA. C-reactive protein (CRP) and serum amyloid A (SAA) were determined pre- and 48 hours postintervention. Patients were followed up to 12 months for the occurrence of postangioplasty restenosis (> or = 50%). When analyzed separately, none of the polymorphisms was associated either with inflammation or restenosis. However, when the IL-1B (-511) and the IL-1RN VNTR genotypes were combined, a highly significant relationship was observed: Non-carriers of the two repeat allele of the IL-1RN VNTR (IL-1RN*2) who were heterozygous and homozygous for the IL-1B (-511)T allele exhibited a gradually increased inflammatory response and a higher restenosis risk. In contrast, carriers of the IL-1RN*2 and the IL-1B (-511)T allele showed a significantly better outcome. This remarkable gene dose-dependent association emphasizes the advantage of considering combinations of genetic markers rather that isolated polymorphisms in the analysis of multifactorial vascular disease.

Aged↗

PubMed2003

Plasminogen activator inhibitor-1 and outcome after femoropopliteal angioplasty: analysis of genotype and plasma levels.

Plasminogen activator inhibitor-1 (PAI-1) is suggested to be involved in the pathophysiology of early thrombosis and late restenosis after percutaneous transluminal angioplasty (PTA). The role of the PAI-1 promoter genotype in this context is indeterminate. We investigated the association of the (4G/5G) polymorphism at nucleotide position (-675) in the PAI-1 gene promoter, PAI-1 plasma levels, and postangioplasty outcome after femoropopliteal PTA. We studied 251 consecutive patients who underwent femoro-popliteal PTA. In a subgroup of 86 patients PAI-1 plasma levels at baseline, 8, 24 and 48 hours postintervention were measured and correlated to the genotype. Patients were followed for early thrombosis and the late restenosis (> or =50%) within 12 months. Multivariate Cox proportional hazards analysis was performed to assess the association between the PAI-1 genotype and PTA failure. Results show that the PAI-1 genotype was neither associated with PAI-1 plasma levels (p=0.40) nor the change of PAI-1 from baseline to 8 (p=0.39), 24 (p=0.86) and 48 hours (p=0.89). Three out of 35 homozygous (4G/4G) patients (9%) had early thrombotic reocclusions, compared to two out of 153 heterozygous (4G/5G) patients (1%) and none of the 63 homozygous (5G/5G) patients (p=0.007). Restenosis after median 5 months (interquartile range 3 to 9) was found in 117 patients (42%), without significant association between the PAI-1 genotype and late postangioplasty failure (Log Rank p=0.95). We can conclude that carriers of the 4G allele exhibited a higher frequency of early thrombotic reocclusions after percutaneous angioplasty. However, the PAI-1 gene promoter polymorphism (4G/5G) was not associated with PAI-1 plasma levels or late postangioplasty restenosis.

Aged↗