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Stephan B Felix

Publications and source records attributed to Stephan B Felix.

At least 37 records · Page 2Linked to original sources
PubMed2005

Seropositivity for anti-Borrelia IgG antibody is independently associated with carotid atherosclerosis.

BACKGROUND: Various infectious agents are associated with atherosclerosis. This analysis was performed to investigate relation between seropositivity for anti-Borrelia IgG and carotid atherosclerosis. METHODS: The cross-sectional Study of Health in Pomerania was conducted in a general community living in a region with endemic Lyme disease. A random sample of 2483 individuals aged 45-79 years was available for the present analysis. Carotid atherosclerosis was sonographically assessed as intima-media thickness of the common carotid artery and as prevalent atherosclerotic plaques in the extracranial carotid arteries. IgG antibodies to Borrelia were determined by ELISA. RESULTS: IgG antibodies to Borrelia were found positive (> 10 IU/mL) in 108 subjects (4.3%). Persons with and without positive anti-Borrelia IgG antibodies differed with respect to carotid intima-media thickness values (0.863 +/- 0.017 mm versus 0.792 +/- 0.004 mm; p < 0.001) and prevalent carotid plaques (odds ratio 2.65, 95% confidence interval 1.53-4.61; p = 0.001), respectively. Seropositivity for anti-Borrelia IgG was also associated with both atherosclerotic endpoints when age, sex and further atherogenic risk factors and confounders were included in multivariable statistical models. CONCLUSIONS: In a region with endemic Lyme disease, seropositivity for anti-Borrelia IgG antibodies is independently associated with atherosclerosis. Our findings add support to the hypothesis that exposure to infectious pathogens increases the atherosclerosis risk.

Adult↗
PubMed2005

Relation of parity with common carotid intima-media thickness among women of the Study of Health in Pomerania.

BACKGROUND AND PURPOSE: Metabolic and hormonal changes associated with pregnancy and childbirth are assumed to contribute to the development of cardiovascular disease among women. We analyzed the association of parity with common carotid intima-media thickness (IMT), which has a predictive value of subsequent myocardial infarction and stroke. METHODS: The Study of Health in Pomerania (SHIP), an epidemiological study of the general population in the northeast of Germany, included 1195 women aged 45 to 79 years. Mean and maximum far-wall IMT of the common carotid arteries were assessed by high-resolution ultrasound. All women were comprehensively characterized as to their reproductive history as well as to socioeconomic, behavioral, and biological risk factors. RESULTS: There was a U-shaped association between the number of children (from 0 to > or =4) and mean and maximum IMT. Nulliparous women had the highest age-adjusted mean (0.81 mm [95% CI, 0.78 to 0.84]) and maximum IMT (1.04 mm [95% CI, 1.00 to 1.09]), and women with single parity the lowest (mean IMT, 0.73 [95% CI, 0.72 to 0.74]; maximum IMT, 0.91 mm [95% CI, 0.89 to 0.93]; P<0.001 versus nulliparity for both parameters). Stepwise multivariate adjustment for socioeconomic factors, lifestyle variables, and biological variables attenuated the magnitude of this association yet significance remained. CONCLUSIONS: Nulliparity and higher number of children are associated with increased carotid IMT. These findings add support to the hypothesis of a link between the reproductive history of women and cardiovascular disease.

Aged↗
PubMed2005

[Assessment of cardiopulmonary function at rest and during exercise in patients with pulmonary hypertension].

Pulmonary hypertension is diagnosed by various investigations that are essential for making the diagnosis. Following a careful history and physical examination, an electrocardiogram, a chest X-ray, lung function studies, blood tests and an echocardiogram form the basis of the diagnostic algorithm. Following these studies, a right and sometimes additional left heart catheterization are carried out to establish the diagnosis and to perform acute vasodilator testing. Most of these studies are performed at rest. However, exercise studies are an important part of the functional assessment in this group of patients. Exercise capacity can be estimated by functional class, measured with the 6-min walk test or comprehensively assessed by cardiopulmonary exercise testing with gas exchange analysis. Once the diagnosis and etiology of pulmonary hypertension have been established, several parameters can predict outcome in these patients: functional class, right ventricular function, pulmonary hemodynamics, and certain laboratory parameters (uric acid, brain natriuretic peptide, troponin, endothelin-1). In addition, exercise parameters such as walking distance, peak oxygen uptake or peak systolic blood pressure can reliably predict prognosis in these patients.

Blood Pressure Determination↗
PubMed2005

Role of immunoglobulin G3 subclass in dilated cardiomyopathy: results from protein A immunoadsorption.

BACKGROUND: Immunoadsorption (IA) by anti-immunoglobulin G (anti-IgG) columns that effectively eliminates total IgG, including IgG3 subclass, represents an additional therapeutic approach in dilated cardiomyopathy (DCM). A recent study revealed that IA with protein A columns does not effectively remove IgG3 and does not induce hemodynamic improvement in DCM. METHODS: Eighteen patients with DCM (left ventricular ejection fraction < or =30%) were included in this case-control study. In all patients, IA with protein A was performed in 4 courses, at 1-month intervals until month 3. Nine patients underwent protein A IA with an improved treatment regimen for IgG3 elimination. Data of these patients were compared retrospectively to existing findings for 9 comparable patients treated by protein A IA with ineffective IgG3 reduction. RESULTS: In both groups, IA induced a comparable reduction of the total IgG level. However, reduction of the IgG3 level was different in the 2 groups (P < .001). Hemodynamics did not significantly change throughout the 3 months in the group with ineffective IgG3 reduction. In contrast, the group with improved IgG3 reduction demonstrated during the first IA course an increase in cardiac index from 2.2 +/- 0.1 to 2.8 +/- 0.2 L min(-1) m(-2) (P < .05). After 3 months before the last IA course, cardiac index was 2.2 +/- 0.1 L min(-1) m(-2) in the group with ineffective IgG3 elimination and 2.8 +/- 0.2 L min(-1) m(-2) in the group with improved IgG3 reduction (P < .01). In the group with ineffective IgG3 reduction, left ventricular ejection fraction increased after 3 months from 21.6 +/- 2% to 24.4 +/- 2% (NS), and from 24.3 +/- 2 to 34.7 +/- 4% in the group with improved IgG3 reduction (P < .05). CONCLUSIONS: Autoantibodies belonging to IgG3 may play an important role in cardiac dysfunction of patients with DCM. Protein A IA in conjunction with an improved treatment regimen for IgG3 elimination induces hemodynamic benefit in patients suffering from DCM.

Adsorption↗
PubMed2005

Tooth loss is independently associated with the risk of acquired aortic valve sclerosis.

BACKGROUND: Several studies have shown that periodontal disease and atherosclerosis are associated. Aortic valve sclerosis (AVS) represents the sum of processes that are similar to the development of atherosclerosis. The present analysis was performed to investigate associations between periodontal disease, tooth loss, and AVS. METHODS: The population-based SHIP was conducted in northeast Germany. A study population of 2341 individuals aged > or =45 years was available for the present analysis. Aortic valve sclerosis was determined by echocardiography. Periodontal status was assessed by attachment loss and tooth loss. RESULTS: The prevalence of AVS was 29.9%. Logistic regression analyses did not reveal attachment loss as an independent risk factor for AVS. However, a reduced number of teeth was independently associated with AVS. Other risk factors for AVS were age, history of myocardial infarction, body mass index, pulse pressure, plasma fibrinogen and lipoprotein (a) levels, and the use of drugs that act on the renin-angiotensin system. CONCLUSION: A reduced number of teeth was independently associated with the risk of AVS. This finding further strengthens the link between oral health and cardiovascular disorders.

Adult↗
PubMed2005

Hemodynamic effects of alpha1-adrenoceptor antagonist, doxazosin, in patients with chronic congestive heart failure.

PURPOSE: Non-selective alpha-adrenoceptor antagonists have not demonstrated significant beneficial effects in chronic heart failure. Previous studies with the selective alpha1-adrenoceptor antagonist, doxazosin, led to conflicting results. We assessed the hypothesis that treatment with doxazosin adjuvant to standard oral therapy results in significant increase in cardiac index in patients with chronic heart failure. METHODS: A double-blind, randomized study was conducted on 30 patients with chronic congestive heart failure (NYHA III-IV), with cardiac index<2.5 l/minxm, and/or with pulmonary capillary wedge pressure>16 mm Hg. Of the 30 patients, 15 were treated with doxazosin and 15 with placebo, both adjuvant to stable oral therapy, which included a minimum of an ACE inhibitor and a diuretic. Hemodynamic measurements were performed on days 1 and 2, and after 12 weeks on study medication. On day 1, patients were treated with 4 mg doxazosin or placebo. On day 2 and throughout the following 12 weeks, the patients were treated with 4 mg or 8 mg doxazosin/d (the latter, if 4 mg/d did not induce an increase >0.75 l/minxm in cardiac index), or with placebo. RESULTS: Six patients were treated with 4 mg doxazosin/d (group A), 9 patients with 8 mg doxazosin/d (group B), and 15 with placebo. Baseline values for the cardiac index on day 1, day 2, and after 12 weeks failed to disclose significant differences between patient groups and between the days of study. On day 1, the increase in cardiac index compared with baseline was significantly higher in group A than in the placebo group (P=0.004) and group B (P=0.001). On day 2, the increase in cardiac index compared with baseline on day 1 was significantly higher in group A than in group B (P=0.003) (with reference to alpha/3=0.0167 according to Bonferroni). This was no longer observed after 12 weeks. In the placebo group, following significant changes occurred in baseline values, heart rate was lower (P=0.023) and stroke volume index was higher after 12 weeks in comparison to day 1 (P=0.032). CONCLUSIONS: In conclusion, oral application of doxazosin supplementary to standard oral medication did not induce sustained hemodynamic benefit. Significant acute increase in cardiac index was observed in a minority (40%) of patients, whereas favorable changes in baseline hemodynamic parameters after 12 weeks occurred in the placebo group.

Adrenergic alpha-Antagonists↗
PubMed2005

Endothelial nitric oxide synthase Glu298Asp gene polymorphism, blood pressure and hypertension in a general population sample.

OBJECTIVE: The Glu298Asp (E/D) polymorphism of the endothelial nitric oxide synthase (eNOS) gene has been related to hypertension. Since several studies have produced contradictory results, this issue is still subject to ongoing debate. We investigated the association of the eNOS E298D polymorphism with hypertension and with blood pressure (BP) in a large population-based sample of Caucasian ethnicity. DESIGN: Cross-sectional study in a random sample of the general population. METHODS: The eNOS E298D polymorphism was determined by 5'-exonuclease assay among 4219 participants aged 20-79 years of the Study of Health in Pomerania (SHIP). RESULTS: The percentages of the EE298, ED298 and DD298 genotypes were 49.2, 42.0 and 8.8%, respectively. The D allele frequencies did not differ between the groups of normotensive and hypertensive subjects (29.7 versus 29.9%, P = 0.812). Similarly, no association could be established between E298D genotype and prevalent hypertension, neither for D allele carriership (multivariate odds ratio 0.97, 95% confidence interval 0.83-1.12) nor for DD homozygosity (multivariate odds ratio 1.10, 95% confidence interval 0.84-1.43). Likewise, genotype groups did not differ as to the distribution of systolic (ANCOVA P = 0.917) or diastolic BP values (ANCOVA P = 0.657). Nearly identical results were obtained if the analyses were repeated sex-specifically or if subjects on antihypertensive medication were excluded. CONCLUSION: In a population-based cohort of Caucasians covering a broad age range, the eNOS E298D polymorphism is neither associated with prevalent hypertension nor with systolic or diastolic BP. These results do not support the hypothesis that the E298D polymorphism contributes to the genetic susceptibility to hypertension.

Adult↗
PubMed2004

The association of thyroid function with cardiac mass and left ventricular hypertrophy.

Decreased serum TSH levels predict cardiovascular mortality, which could be explained by left ventricular hypertrophy (LVH). The aim of this analysis was to investigate the association between thyroid function and LVH. The population-based Study of Health in Pomerania was conducted in a previously iodine-deficient area. Data of 1510 individuals at least 45 yr of age with echocardiography and without thyroid disorders were analyzed. LVH was defined as a left ventricular mass index (LVMI) exceeding 150 g/m(2) (men) or 120 g/m(2) (women). Overt hyperthyroidism was associated with LVMI (P < 0.01), whereas euthyroid subjects and those with elevated TSH levels did not significantly differ with regard to LVMI. LVH was observed in three (15.0%) subjects with elevated serum TSH levels, in 127 (10.5%) euthyroid persons, in 24 (12.5%) individuals with decreased serum TSH levels, and in four (57.1%) subjects with hyperthyroidism (P < 0.01). Logistic regression analysis identified overt hyperthyroidism as an independent risk factor for LVH (odds ratio, 13.65; 95% confidence interval, 2.83-65.75; P < 0.01). There is an association between thyroid function status, cardiac mass, and LVH. Hyperthyroidism is an independent risk factor for LVH.

Blood Pressure↗
PubMed2004

Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy.

OBJECTIVES: This research was conducted to evaluate the role played by the humoral immune system in cardiac dysfunction among dilated cardiomyopathy (DCM) patients, as enabled by immunoadsorption therapy (IA) that effectively removes functionally active cardiac autoantibodies from plasma. BACKGROUND: Various circulating autoantibodies have been detected among patients suffering from DCM. METHODS: Before IA, antibodies were purified from plasma of 45 DCM patients (left ventricular ejection fraction [LVEF] <30%). We analyzed the functional effects of antibodies (300 mg/l) on calcium transients and on systolic cell shortening in adult rat cardiomyocytes. After this in vitro analysis, IA was performed in four courses at one-month intervals until month 3. RESULTS: Antibodies from 29 patients induced a reduction (>10%) in calcium transients (mean reduction: -16.5 +/- 1.9%) and a simultaneous reduction (>10%) of cell shortening (mean reduction: -21.2 +/- 1.8%) on cardiomyocytes (p < 0.001) (cardiodepressant group). Antibodies from 16 patients did not significantly influence calcium transients and cell shortening (<10%) (non-cardiodepressant group). During the first IA course, the cardiodepressant group demonstrated an acute increase in cardiac index (CI) from 2.2 +/- 0.1 l/min/m(2) to 2.9 +/- 0.1 l/min/m(2) (p < 0.001). In the non-cardiodepressant group, hemodynamics did not significantly change throughout three months. After three months before the final IA course (prolonged effects), the CI was 2.1 +/- 0.1 l/min/m(2) in the non-cardiodepressant group and 2.9 +/- 0.1 l/min/m(2) in the cardiodepressant group (p < 0.001). After three months LVEF increased only in the cardiodepressant group: from 20.8 +/- 1% to 30.5 +/- 1% (p < 0.01). CONCLUSIONS: In the majority of DCM patients, disturbances of humoral immunity with production of cardiodepressant antibodies may play a functional role in cardiac dysfunction. Evidence of cardiodepressant antibodies predicts hemodynamic benefits during IA.

Animals↗
PubMed2004

Association between high serum ferritin levels and carotid atherosclerosis in the study of health in Pomerania (SHIP).

BACKGROUND AND PURPOSE: Several studies have provided evidence for a relationship between body iron load and cardiovascular disease. We analyzed the association of serum ferritin levels with carotid atherosclerosis. METHODS: We assessed intima-media thickness and plaque prevalence in the carotid arteries by high-resolution ultrasound among 2443 participants (1200 women; age, 45 to 79 years) in the Study of Health in Pomerania (SHIP), a population-based study in northeast Germany. RESULTS: In multivariate analysis, serum ferritin levels were not independently associated with carotid intima-media thickness among women or men. In contrast, the relationship between serum ferritin levels and carotid plaque prevalence was significant among men (odds ratio per 1-SD increase of serum ferritin levels, 1.33; 95% confidence interval, 1.08 to 1.44) yet not among women (odds ratio, 1.29; 95% confidence interval, 0.98 to 1.75). However, both men and women showed a dose-response relation between serum ferritin levels and carotid atherosclerosis in which higher serum ferritin levels were associated with greater odds ratios for carotid plaque prevalence. Additionally, there was an interaction of serum ferritin levels with low-density lipoprotein (LDL) cholesterol (P=0.039) among men in which the association of serum ferritin levels with carotid plaque prevalence became stronger with increasing LDL cholesterol levels. CONCLUSIONS: Our study identified a relationship between serum ferritin levels and carotid atherosclerosis that was potentiated by LDL cholesterol. This relationship adds support to the hypothesis of a link between iron and cardiovascular disease.

Aged↗
PubMed2004

Hepatitis B and C virus infection and the risk of atherosclerosis in a general population.

BACKGROUND: The development of atherosclerosis has an inflammatory component. Currently it is not clear, whether hepatitis B and C virus infections are associated with the risk of atherosclerosis. The aim of the present analysis was to investigate those relationships in a population sample. METHODS AND RESULTS: The study of health in Pomerania (SHIP) is a cross-sectional study of the adult population in the northeast of Germany. HBs antigen (HBsAg) and IgG antibodies against hepatitis B and C virus (anti-HBs and anti-HCV) were determined by enzyme linked immunosorbent assays. Fifteen subjects (0.4%) were positive for HBsAg, and 21 subjects (0.5%) were positive for anti-HCV. Among the persons who had no history of anti-hepatitis B vaccination, 213 individuals (5.0%) were found to be as positive for anti-HBs. These individuals and those with prevalent anti-HCV antibodies were regarded as cases (n = 233). The control group comprised of 4033 individuals. Multivariable analyses revealed that there was no independent association between anti-HBs and anti-HCV antibody seropositivity and atherosclerotic end-points such as prevalent myocardial infarction, stroke, carotid intima-media thickness (IMT), carotid plaques and stenoses. CONCLUSION: There is no association between serological markers for hepatitis B and C virus infection and the risk of atherosclerosis in this population sample.

Adult↗
PubMed2004

Immunoadsorption in idiopathic dilated cardiomyopathy, a 3-year follow-up.

OBJECTIVE: Recent studies have shown that immunoadsorption (IA) leads to improvements in left ventricular function and in functional status in selected patients with idiopathic dilated cardiomyopathy (DCM) and circulating autoantibodiesautoantibod. Most of the few studies dealing with this topic describe only short-term results. The aim of this study was to ascertain the prolonged effects of IA over a period of 3 years. MATERIALS AND METHODS: Our study included nine patients with circulating beta1-adrenoreceptor antibodies who suffered from idiopathic DCM (left ventricular ejection fraction <30%). IA was performed using an adsorber against immunoglobulins (Ig Therasorb, Baxter). During therapy and after 3 months, hemodynamic parameters were monitored using a Swan-Ganz thermodilution catheter. All patients were monitored under clinical and echographical examinations over a period of at least 3 years. RESULTS: During IA hemodynamic measurements show increases in both cardiac and stroke volume index (from 2.0 (S.E.M. 0.16) to 3.0 (S.E.M. 0.32) l min(-1) m(-2), and from 26.1 (S.E.M. 2.63) to 38.9 (S.E.M. 3.56) ml/m2, respectively). Hemodynamic stabilization was observed after the following 3 months (CI 2.6 (S.E.M. 0.14) l min(-1) m(-2), SVI 37.9 (S.E.M. 2.14) ml/m2). After 36 months five patients were still alive. Antibody titers increased in patients who deteriorated. The five patients who are still alive show an increase in left ventricular ejection fraction and no significant increase in antibody titers. CONCLUSION: Immunoadsorption may improve short-term hemodynamics as well as long-term follow-up of patients with severe idiopathic dilated cardiomyopathy. Increase in antibody titers is accompanied by deterioration of cardiovascular function.

Autoantibodies↗
PubMed2004

Plasma fibrinogen levels are associated with a strong family history of myocardial infarction.

Family history of myocardial infarction (MI) is a known risk factor for coronary artery disease (CAD). The aim of the present study was to investigate whether there is a specific risk factor profile for CAD in individuals with a strong family history of MI occurring at any age. The Study of Health in Pomerania is a cross-sectional, population-based study in the north-east of Germany. A random sample was drawn from the population aged 20-79 years. From 3793 subjects with siblings, 34 (0.9%) reported a history of MI in at least one parent and one sibling. We matched these cases with 136 controls (1 : 4 matching for age, sex and presence of sibling). We then compared cases and controls with respect to known risk factors for MI. Subjects with a dual parental and sibling history of MI had higher plasma fibrinogen levels (3.5 versus 3.0 g/l, respectively), and also more often angina pectoris than the matched controls (P < 0.05). Multivariable analysis revealed an independent association between dual parental and sibling history of MI and plasma fibrinogen levels. We conclude that plasma fibrinogen levels may indicate an inheritable risk for CAD in subjects with a strong family history of MI.

Adult↗
PubMed2004

Thyroid function and carotid wall thickness.

Decreased serum TSH levels predict vascular mortality in older people. There is a need to investigate mechanisms that could explain this association. This study was designed to investigate the relationship between thyroid function and the carotid intima-media thickness (IMT). The Study of Health in Pomerania is a population-based survey in Germany. Data from 2086 individuals at least 45 yr old with carotid ultrasound and without known thyroid disorders were analyzed. Twenty-nine participants (1.4%) had elevated serum TSH levels, 300 (14.4%) had decreased serum TSH levels, and 12 (0.6%) participants were hyperthyroid. A linear relationship between thyroid function and IMT was found. The highest IMT values were observed in participants with hyperthyroidism, the lowest in subjects with elevated serum TSH levels (P < 0.01). A multivariable regression analysis identified thyroid function as an independent risk factor for increased IMT. Other risk factors for increased IMT included male gender, advanced age, diabetes mellitus, current smoking, and the use of antihypertensive medication; increased pulse pressure, serum low-density cholesterol, and total cholesterol/high-density lipoprotein ratio; as well as a decreased heart rate and a positive history of myocardial infarction. We conclude that there is an independent association between thyroid function and the IMT of the carotid artery.

Carotid Arteries↗
PubMed2003

Beta1-adrenoceptor antibodies induce apoptosis in adult isolated cardiomyocytes.

beta(1)-Adrenoceptor autoantibodies are present in about 30% of patients suffering from dilated cardiomyopathy. The apoptotic effects mediated by beta(1)-adrenoceptor antibodies remain to be studied. Monoclonal antibodies were raised against a synthetic peptide corresponding to the second extracellular loop of the human beta(1)-adrenoceptor in balb/C mouse, and were characterized by enzyme immunoassay. Purified immunoglobulin G from nonimmunized animals (controls) did not influence the rate of apoptosis. beta(1)-Adrenoceptor antibodies caused a dose-related increase in apoptotic cells: annexin test (dilution 1:2: 21+/-1.1% apoptotic cells vs. 4+/-0.4% apoptotic cells in controls; p<0.01); TdT-mediated dUTP nick end labeling (TUNEL) test (dilution 1:2: 26+/-2% apoptotic cells vs. 10+/-2% apoptotic cells in controls; p<0.01). The effect of the beta(1)-adrenoceptor antibodies was blocked by the antigenic peptide and by the antagonist metoprolol (10 micromol/l). The apoptotic effect induced by isoproterenol was attenuated by the beta(1)-adrenoceptor antibody. After pre-incubation of cardiomyocytes with the protein kinase A inhibitor Rp-Adenosine-3',5'-cyclic monophosphothioate triethylamine (RpcAMPS), beta(1)-adrenoceptor antibody was not capable of inducing an increase of the rate of apoptosis. beta(1)-Adrenoceptor antibodies induced apoptosis in adult rat cardiomyocytes via the protein kinase A cascade.

Adrenergic beta-Agonists↗
PubMed2003

Interaction of CA repeat polymorphism of the endothelial nitric oxide synthase and hyperhomocysteinemia in acute coronary syndromes: evidence of gender-specific differences.

We have recently shown that high CA repeat copy numbers (> or = 34 repeats) in intron 13 of the endothelial nitric oxide (eNOS) gene are associated with excess risk of coronary artery disease. Hyperhomocysteinemia interacts by several mechanisms with the NO system, thereby favoring endothelial dysfunction. Since hyperhomocysteinemia evidently promotes prothrombotic activation, we investigated a possible interaction among hyperhomocysteinemia, the eNOS CA repeat polymorphism, and acute coronary syndromes. The median value of homocysteine in our study population was 9.4 micromol/l. We accordingly determined the relative risk of acute coronary syndromes for homocysteine values higher than 9.4 micromol/l and 9.4 micromol/l or lower in the entire coronary artery disease group, and at different CA repeat cutoff values (34, 35, 36, 37, 38 CA repeats). For the entire coronary artery disease group ( n=1000), homocysteine levels higher than 9.4 micromol/l were not significantly associated with acute coronary syndromes. Although the CA repeat copy numbers were not associated with acute coronary syndromes in the overall group, the relative risk among women with homocysteine higher than 9.4 micromol/l for developing acute coronary syndromes increased nonsignificantly from 0.98 at cutoff 34 CA repeats to 1.68 at 35 CA repeats and significantly to 4.89 at 36 CA repeats, 11.20 at 37 CA repeats, and 18.32 at 38 CA repeats. This effect modification was not observed in men. These data suggest gender-specific gene-environment interaction between the CA repeat eNOS polymorphism and homocysteine in acute coronary syndromes.

Acute Disease↗
PubMed2003

Activation of Akt is essential for acetylcholine to trigger generation of oxygen free radicals.

OBJECTIVES: Acetylcholine (ACh) receptor activation in the heart causes mitochondrial production of reactive oxygen species (ROS) that is dependent on mitochondrial K(ATP) channel opening. Recent data show that Akt (also known as protein kinase B) is phosphorylated at its activation site following exposure to ACh. However, since no reliable Akt inhibitor is available, it has not been possible to determine whether Akt activation is an actual step in the protective pathway. METHODS: Cultured rat vascular smooth muscle cells (A7r5) were transiently transfected with a dominant negative Akt (Akt-AAA), thus inhibiting the ability of ACh in these cells to phosphorylate Akt. Transfected cells were identified by co-transfection of enhanced green fluorescent protein (EGFP). ROS production was determined by incubating the cells for 15 min with 1 mM reduced MitoTracker Red which becomes fluorescent only after reacting with ROS. Cells were then triple-washed to remove any voltage-dependent pool of dye and single cell fluorescence was measured. RESULTS: ACh exposure (2 mM) led to a 1.64+/-0.15-fold increase in the average fluorescence over that seen in untreated cells (P=0.002). A similar increase in ROS production occurred after treatment with either the K(ATP) channel opener diazoxide (DIAZ) or the potassium ionophore valinomycin (VAL). Akt-AAA transfection abolished ACh-induced ROS production, but not increased ROS production after treatment with either DIAZ or VAL. CONCLUSION: Thus, at least in the smooth muscle cell model, Akt phosphorylation is an important step in the signal transduction pathway leading from ACh receptor activation to the generation of ROS. The experiments reveal that Akt is positioned between the receptor and the K(ATP) channel in this model.

Acetylcholine↗