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Angela M Carter

Publications and source records attributed to Angela M Carter.

11 recordsLinked to original sources
PubMed2006

Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study.

The renin-angiotensin system is a key regulator of blood pressure (BP), with inhibitors of angiotensin-converting enzyme (ACE) used clinically to treat hypertension and other cardiovascular conditions. ACE2 is a newly identified member of this system, which converts angiotensin II to angiotensin, and of which the occurrence in plasma has not been investigated. The aim of this study was to determine the heritability of circulating ACE, ACE2, and neprilysin (NEP), which may also be a regulator of BP, in a family study, and to determine covariates that contribute to the variation in plasma activity. ACE, ACE2, and NEP activities were measured in plasma from 534 subjects in the Leeds Family Study using selective fluorogenic substrates. Genetic factors accounted for 24.5%, 67%, and 22.7% of the phenotypic variation in circulating ACE, ACE2, and NEP, respectively. ACE insertion/deletion polymorphism and other measured covariates accounted for 23.8% of variance in circulating ACE. High-density lipoprotein cholesterol was a significant determinant of circulating ACE2. Measured covariates accounted for 17.3% of variation in circulating NEP. ACE and NEP were associated with systolic and diastolic BP in univariate analyses; however, only ACE was independently associated with systolic and diastolic BP after accounting for covariates and shared childhood household.

Adult↗
PubMed2006

Complement C3 and C-reactive protein are elevated in South Asians independent of a family history of stroke.

BACKGROUND AND PURPOSE: Complement components are emerging risk factors for cardiovascular disease. In this study, we examined the relation among C3, C-reactive protein (CRP), factor B, and features of the insulin resistance (IR) syndrome in 143 first-degree relatives of South Asian subjects with ischemic stroke, 141 South Asian controls, and 121 white controls. METHODS: C3, CRP (high-sensitivity assay), and factor B levels were measured by ELISAs, and their relation to features of the IR syndrome were assessed. Data are presented as geometric mean (95% CI). RESULTS: There was no significant difference in the levels of C3 between South Asian relatives (1.25 [1.21, 1.29] g/L) and South Asian controls (1.20 [1.15, 1.24] g/L, P=0.2). Levels in both South Asian groups were significantly higher than in white controls (0.95 [0.92, 0.98] g/L; P<0.001 for both comparisons). These differences remained significant after adjustment for covariates. Similarly, levels of CRP were not different between the 2 South Asian groups, but levels in both South Asian groups, after adjustment for covariates, were significantly higher than in white controls. There was no difference in the levels of factor B among the 3 groups. South Asian subjects with elevated C3 levels clustered risk factors associated with IR to a greater extent than those with high CRP. CONCLUSIONS: These results suggest that South Asians have a greater level of chronic subclinical inflammation than do whites, independent of a family history of stroke. In addition, C3 is more likely to cluster with features of the IR syndrome compared with CRP in South Asians.

Adult↗
PubMed2005

Complement C3 and C-reactive protein levels in patients with stable coronary artery disease.

The aim of this study was to determine whether complement C3 is an indicator of coronary artery disease (CAD). We measured plasma C3 and CRP levels in 278 patients undergoing coronary angiography for typical symptoms of CAD and 269 healthy age and sex matched controls. C3 levels were significantly higher in patients compared with controls (1.15 g/l and 0.92 g/l respectively; p<0.001). In the patient group, C3 levels correlated with BMI, fasting glucose, HbA1c, fibrinogen, CRP and HDL in both men and women. CRP levels were also higher in patients compared with controls (1.14 mg/l and 0.86 mg/l respectively; p=0.005) and correlated with markers of the metabolic syndrome. In a logistic regression model including C3, smoking, hypertension, cholesterol and diabetes, C3 was independently associated with CAD with an odds ratio of 3.20 for a 1 SD increase in C3 levels. In contrast, CRP was not independently associated with CAD in a similar regression analysis. In conclusion, both C3 and CRP plasma levels are elevated in patients with symptoms of CAD. However, C3 seems to be a better indicator of CAD than CRP in this study, suggesting that C3 could be an additional marker for risk stratification in atherosclerosis.

Biomarkers↗
PubMed2005

The application of proteomics to diabetes.

Poteomics is the investigation of all the proteins and their various modifications making up a system, be that a cell, tissue or organism. The techniques involved in proteomics allow the global screening of complex samples of proteins and provide qualitative and quantitative evidence of altered protein expression. This lends itself to the investigation of the molecular mechanisms underpinning disease processes and the effects of treatment. This review describes the main techniques of proteomics and how they have begun to be applied to diabetes research.

Adipose Tissue↗
PubMed2005

Inflammation, thrombosis and acute coronary syndromes.

Inflammation plays a central role in the pathogenesis of acute coronary syndromes, the prevalence of which is increased in individuals with diabetes. Monocytes and macrophages, T cells and mast cells contribute to the initiation, development and rupture of atherosclerotic plaques by synthesising a variety of pro-inflammatory cytokines, including interleukin 1beta, interleukin 6 and tumour necrosis factor alpha. Cytokines upregulate endothelial cell adhesion molecules, recruit leukocytes and induce smooth muscle cell migration and proliferation. Cytokines act systemically to initiate the acute phase response, up-regulating proteins involved in inflammation and haemostasis and resulting in a pro-inflammatory and pro-thrombotic state. Expression of tissue factor by inflammatory cells potently induces thrombus formation upon plaque rupture, leading to acute coronary syndromes. Inflammatory biomarkers, including C-reactive protein, complement proteins, interleukin 6 and white blood cell count, predict development of acute coronary syndromes. C-reactive protein has been widely studied and consistently predicts future acute coronary syndrome events.

Acute Disease↗
PubMed2003

Genetic regulation of fibrin structure and function: complex gene-environment interactions may modulate vascular risk.

BACKGROUND: Polymorphisms in the fibrinogen and factor XIII genes are associated with atherothrombotic risk, but clinical studies have produced inconsistent results and laboratory studies have not explained these findings. We aimed to investigate interactions between polymorphisms in the factor XIII and fibrinogen genes, fibrinogen concentrations, and other cardiovascular risk factors in relation to fibrin structure and function. METHODS: We used permeation analysis and electron microscopy to investigate interactions between fibrin structure, factor XIII Val34Leu, fibrinogen Aalpha Thr312Ala, fibrinogen Bbeta Arg448Lys, and fibrinogen concentrations in plasma and purified systems. FINDINGS: Increased fibrinogen concentrations were associated with decreases in permeability, with tighter clot structures in the presence of factor XIII 34Val alleles compared with those in the presence of 34Leu alleles. Findings were confirmed by scanning electron microscopy of fibrin. Similar changes in permeability were noted for Aalpha fibrinogen 312Ala compared with that for 312Thr. INTERPRETATION: Our results show interactions between coding polymorphisms in fibrinogen and factor XIII and fibrinogen concentrations that modify fibrin and explain the apparent paradox between epidemiological studies of factor XIII 34Leu and reported in-vitro effects on fibrin structure and function. We suggest a potential complexity of gene-gene and gene-environment interactions in determining cardiovascular risk.

Aged↗
PubMed2003

Functional analysis of the fibrinogen Aalpha Thr312Ala polymorphism: effects on fibrin structure and function.

BACKGROUND: The fibrinogen Aalpha Thr312Ala polymorphism occurs within the alphaC domain of fibrinogen, which is important for lateral aggregation and factor XIII-induced cross-linking of fibrin fibers. We have previously shown an association of Ala312 fibrinogen with poststroke mortality in subjects with atrial fibrillation and with pulmonary embolism in subjects with venous thrombosis. METHODS AND RESULTS: We studied the properties of clots formed from purified Ala312 and Thr312 fibrinogen and found that Ala312 fibrinogen produces stiffer clots, associated with increased alpha chain cross-linking, as demonstrated by SDS-Page. On electron microscopy analysis, we found larger fiber diameters in the Ala312 clots and observed a lower number of fibers per square micrometer. The number of branch points per square micrometer was similar between genotypes. CONCLUSIONS: Our study shows that Ala312 influences clot structure and properties by increased factor XIII cross-linking and formation of thicker fibrin fibers. These findings may provide a mechanism by which Ala312 fibrinogen could predispose to clot embolization.

Blood Coagulation↗
PubMed2002

Increased fibrinogen levels among South Asians versus Whites in the United Kingdom are not explained by common polymorphisms.

Determinants of fibrinogen level among South Asians are not established. In 1997-1999, plasma fibrinogen levels and prevalences of the fibrinogen polymorphisms A alpha Thr312Ala, beta-445G/A, and B beta Arg448Lys and correlates were compared among 100 apparently healthy United Kingdom South Asians and 100 age- and sex-matched Whites. Mean fibrinogen levels were higher in South Asians (3.33 g/liter, 95% confidence interval (CI): 3.16, 3.51) than in Whites (2.84 g/liter, 95% CI: 2.72, 2.96) (p < 0.0001), but genotype distributions were similar. B beta Arg448Lys was related to fibrinogen in South Asians (RR (n = 67): 3.22 g/liter, 95% CI: 3.03, 3.43; RK (n = 26): 3.72 g/liter, 95% CI: 3.65, 4.11; KK (n = 7): 3.07 g/liter, 95% CI: 2.53, 3.72) (p = 0.04) and Whites (p = 0.06). beta-455G/A was related to fibrinogen in Whites (GG (n = 56): 2.68 g/liter, 95% CI: 2.56, 2.86; GA (n = 37): 2.97 g/liter, 95% CI: 2.79, 3.17; AA (n = 5): 3.22 g/liter, 95% CI: 2.85, 3.65) (p = 0.02) and South Asians (p = 0.07). After adjustment for age, gender, body mass index, hypertension, cholesterol, triglycerides, smoking, A alpha Thr312Ala, and beta-455G/A, fibrinogen levels remained significantly higher in South Asians (3.56 g/liter, 95% CI: 3.35, 3.77) than in Whites (3.03 g/liter, 95% CI: 2.85, 3.22) (p < 0.0001). These findings suggest that increased fibrinogen levels among South Asians versus Whites are not due to differences in the prevalence of genetic polymorphisms that encode for fibrinogen.

Adult↗
PubMed2002

Factor XIII A-subunit concentration predicts outcome in stroke subjects and vascular outcome in healthy, middle-aged men.

There is growing evidence for a role of factor XIII (FXIII) in vascular disease. FXIII measures were determined in (i) a nested case-control study from the Second Northwick Park Heart Study of 63 men with myocardial infarction (MI) and 124 age-matched controls and (ii) in a case-control study of 475 subjects with acute stroke and 461 controls followed up for 54 months for mortality. In both studies, measures of FXIII A- and B-subunit antigen, FXIII activity and prothrombin fragments (F1 + 2) were made. An in vitro model was used to investigate the effects of thrombin activity on FXIII A- and B-subunit antigen levels. In study 1, patients clinically free of coronary artery disease who later developed MI had lower adjusted FXIII A-subunit levels at recruitment (129.2%vs 113.3%, P = 0.007). In study 2, stroke patients with large vessel disease had lower A-subunit antigen levels (102.1%vs 127.2%, P < 0.001), but higher F1 + 2 levels (0.941%vs 0.753%, P < 0.05), than subjects with small vessel disease. Levels of FXIII A-subunit (100%vs 117%, P < 0.0001) were lower and F1 + 2 higher (1.020%vs 0.702%, P < 0.0001) in stroke patients who had died compared with those still alive at the end of the follow-up period. Low concentrations of FXIII A-subunit antigen predicted vascular outcome in otherwise healthy subjects and relate to both size of infarct and poor post-stroke survival in patients with acute ischaemic stroke. Low in vitro concentrations of FXIII A-subunit antigen wererelated to increased thrombin generation and, thus, increased risk of thrombotic events.

Aged↗
PubMed2002

Prothrombin G20210A is a bifunctional gene polymorphism.

The G20210A polymorphism has been shown to alter the efficiency of prothrombin mRNA processing. Here we show that the G20210A mutation also alters prothrombin mRNA stability. Three-fold more prothrombin protein and mRNA were produced in NIH-3T3 cells transfected with the prothrombin cDNAs containing the 20210A variant compared to cells expressing the 20210G variant. mRNA stability assays using chimeric globin transcripts harboring the G or A variant of the 97 nt prothrombin 3'-UTR indicated that the 20210G variant conferred greater instability to the globin reporter transcript than the A variant in transfected HepG2 cells. Both variants of the prothrombin 3'-UTR were shown to provide binding sites for a number of cellular proteins including HuR, an RNA binding protein associated with mRNA stability. Our results indicate that the G20210A is a bifunctional polymorphism, as it not only alters the efficiency of mRNA processing, but also the decay rate of prothrombin mRNA.

3' Untranslated Regions↗