Endothelial FOS expression and pre-eclampsia.

Objective: To study gene expression profiles in human endothelial cells incubated with plasma from women who developed pre-eclampsia and women with normotensive pregnancies.

Design: A case-control study.

Setting: A longitudinal nested case-control study within three maternity units.

Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes.

B-type natriuretic peptide predicts postoperative cardiac events and mortality after elective open abdominal aortic aneurysm repair.

Objective: The aim of this study was to determine if a single preoperative B-type natriuretic peptide (BNP) level correlated with perioperative cardiac events, cardiac death, and all-cause mortality in elective open abdominal aortic aneurysm (AAA) repair in the short term, intermediate term, and long term.

Methods: A prospective, 2-year multicenter observational cohort study in the three vascular units in Glasgow was performed. All patients who were admitted for elective open AAA repair were recruited.

Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes.

The aim of the present study was to determine whether the endothelial dysfunction associated with CAD (coronary artery disease) and T2D (Type 2 diabetes mellitus) is concomitant with elevated mtROS (mitochondrial reactive oxygen species) production in the endothelium and establish if this, in turn, regulates the activity of endothelial AMPK (AMP-activated protein kinase). We investigated endothelial function, mtROS production and AMPK activation in saphenous veins from patients with advanced CAD. Endothelium-dependent vasodilation was impaired in patients with CAD and T2D relative to those with CAD alone.

Integrase-deficient lentiviral vectors mediate efficient gene transfer to human vascular smooth muscle cells with minimal genotoxic risk.

We have previously shown that injury-induced neointima formation was rescued by adenoviral-Nogo-B gene delivery. Integrase-competent lentiviral vectors (ICLV) are efficient at gene delivery to vascular cells but present a risk of insertional mutagenesis. Conversely, integrase-deficient lentiviral vectors (IDLV) offer additional benefits through reduced mutagenesis risk, but this has not been evaluated in the context of vascular gene transfer.

Proteomics in hypertension.

Proteomics, the study of the proteins making up the proteome, has emerged in recent years as an important tool in several different fields of medical research for early disease detection, for assessment of response to treatment and for unravelling underlying pathophysiological mechanisms. Although the majority of patients with hypertension are treated in a similar manner, the causes underlying the condition are diverse, and often poorly understood. Genetic studies have implicated several different candidate genes, but it may be that examination of the 'downstream' products of genes, the proteins, will help to improve understanding of the link between the environmental and genetic effects that contribute towards development of hypertension.

Proteomics in hypertension and other cardiovascular diseases.

Hypertension is a major cardiovascular risk factor with a multifactorial pathogenesis, including genetic and environmental factors. In addition to hypothesis-driven strategies, unbiased approaches such as genomics, proteomics, and metabolomics are useful tools to help unravel the pathophysiology of hypertension and associated organ damage. During development of cardiovascular disease the key organs and tissues undergo extensive functional and structural changes that are characterized by alterations in the amount and type of proteins that are expressed.

Urinary proteomics to support diagnosis of stroke.

Accurate diagnosis in suspected ischaemic stroke can be difficult. We explored the urinary proteome in patients with stroke (n = 69), compared to controls (n = 33), and developed a biomarker model for the diagnosis of stroke. We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry.

Risk stratification scores in elective open abdominal aortic aneurysm repair: are they suitable for preoperative decision making?

Objectives: Risk indices help quantify the risk of cardiovascular events and death prior to making decisions about prophylactic AAA repair. This paper aims to study the predictive capabilities of 5 validated indices.

Design And Methods: A prospective observational multi-centre cohort study from August 2005 to September 2007 in Glasgow recruited 106 consecutive patients undergoing elective open AAA repair.

Implementation of proteomic biomarkers: making it work.

While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification.

Genetics and hypertension: is it time to change my practice?

Recent advances in genotyping technology and in particular a number of large-scale genome-wide association studies have helped to unravel the genetic basis of hypertension. Although our knowledge is still far from being complete it is important to ask how genetic findings could be translated to clinical practice. In a first step we summarize the strategies to dissect the genetics of hypertension from candidate gene studies to genome-wide association studies and recent sequencing experiments.

Early pregnancy soluble E-selectin concentrations and risk of preeclampsia.

Objective: Circulating biomarkers of endothelial dysfunction and inflammation are elevated in late pregnancy in women with preeclampsia. We examined plasma levels of inflammatory cytokines and adhesion molecules in early pregnancy, to assess their ability to predict preeclampsia.

Methods: In a prospective longitudinal study, 2600 women with singleton pregnancies and no history of hypertension were recruited at their antenatal hospital (booking) visit at gestational week 12-16.

Role of microRNAs 99b, 181a, and 181b in the differentiation of human embryonic stem cells to vascular endothelial cells.

MicroRNAs (miRNAs) are short noncoding RNAs, which post-transcriptionally regulate gene expression. miRNAs are transcribed as precursors and matured to active forms by a series of enzymes, including Dicer. miRNAs are important in governing cell differentiation, development, and disease.

Association of central and peripheral pulse pressure with intermediate cardiovascular phenotypes.

Objective: We assessed the relationship between pulse pressure and intermediate cardiovascular phenotypes in a middle-aged cohort with high prevalence of hypertension.

Background: It has been suggested that central pulse pressure (cPP) is a better predictor of cardiovascular outcome than peripheral pulse pressure (pPP), particularly in the elderly. Yet, it is unclear if cPP provides additional prognostic information to pPP in younger individuals.

Blood pressure loci identified with a gene-centric array.

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples.

A pilot study on the effect of short-term consumption of a polyphenol rich drink on biomarkers of coronary artery disease defined by urinary proteomics.

Polyphenol rich diets have been associated with a reduced risk of cardiovascular disease. We examined the effect of a polyphenol rich (P-R) drink on biomarkers assessed by urinary proteomics. Thirty nine middle aged and overweight subjects were randomized to P-R drink (n = 20) or placebo (n = 19) in addition to their normal diet.

Peripheral arterial tone: assessment of microcirculatory function in pregnancy.

Objective: Endothelial dysfunction is known to play a key role in the pathogenesis of preeclampsia, but the majority of methods for its detection are too invasive to be used in pregnancy. In this study we report a novel method - peripheral arterial tonometry (PAT) - for examining microcirculatory function in pregnancy.

Methods: One hundred and eighty women with at least two risk factors for preeclampsia were examined at gestational weeks 16 and 28; 80 women were examined at 6-9 months postnatally.

Urinary proteomics in the assessment of chronic kidney disease.

Purpose Of Review: Urinary proteomics has emerged as an approach that could deliver relevant clinical information. In this review, we aim at highlighting the recent developments, especially with respect to clinical implementation. We review several of the recent publications reporting on larger cohorts, focusing on those that aim at qualification and/or validation of urinary proteomics biomarkers.

Urinary proteomics in cardiovascular disease: Achievements, limits and hopes.

Cardiovascular disease (CVD) is the major cause of mortality and morbidity worldwide. Diagnosis of CVD and risk stratification of patients with CVD remains challenging despite the availability of a wealth of non-invasive and invasive tests. Clinical proteomics analyses a large number of peptides and proteins in biofluids.

Association of (pro)renin receptor gene polymorphism with blood pressure in Caucasian men.

The renin-angiotensin system is a major regulatory system of cardiovascular and renal function. Recently, (pro)renin receptor [(P)RR] was identified as new component of the renin-angiotensin system. The IVS5+169C>T polymorphism of the (P)RR gene was shown to be associated with blood pressure (BP) in Japanese men, but no data are available for Caucasians.

Serum phosphate and outcome at one year after deceased donor renal transplantation.

Traditional risk factors do not adequately explain the increased prevalence of cardiovascular disease in renal patients. This study considered a "non-traditional" risk factor, serum phosphate and outcome in renal transplant recipients. Data from 377 patients who received a first deceased donor renal transplant between January 1, 1999, and December 31, 2008, were recorded; 10% (n=38) had diabetes, 16.

Reduction in basal nitric oxide activity causes albuminuria.

Objective: The barrier function of the glomerular filter has been studied for decades. Albuminuria reflects a malfunction of this barrier, and in animals dysfunctional endothelial nitric-oxide (NO) synthase results in albuminuria. We aimed to analyze the importance of NO for the glomerular barrier function in humans.

Urinary proteomics for prediction of preeclampsia.

Preeclampsia is a major determinant of fetal and maternal morbidity and mortality. We used a proteomic strategy to identify urinary biomarkers that predict preeclampsia before the onset of disease. We prospectively collected urine samples from women throughout pregnancy.

Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.

Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.

Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants.