Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies.

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs.

Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies.

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be mitochondrial UCPs.

Duration of preceding hypertension is associated with prolonged length of ICU stay.

Background: A substantial proportion of patients suffer prolonged length of intensive care unit stay (PLOS) or prolonged mechanical ventilation (PMV) following coronary artery bypass grafting (CABG). Identifying factors associated with PLOS and PMV would aid in patient risk stratification. We sought to identify the factors associated with PLOS and PMV following CABG.

Higher IL-6 levels but not IL6 -174G>C or -572G>C genotype are associated with post-operative complication following coronary artery bypass graft (CABG) surgery.

Large increases in inflammatory markers, particularly IL-6, occur after cardiac surgery. However, despite interventions to reduce the inflammatory response, great variability still remains which could in part be attributable to genetic predisposition. Since increased IL-6 levels following surgery are also associated with poorer outcome we sought to determine whether baseline and post-operative levels of Interleukin-6 (IL-6) and functional common variants of the Interleukin-6 (IL6) gene are associated with post-operative outcome following coronary artery bypass grafting (CABG).

Rhabdomyolysis with atorvastatin and fusidic acid.

Rhabdomyolysis is a rare but life-threatening complication of statin therapy. A 74-year-old man, treated with atorvastatin, developed rhabdomyolysis after the co-administration of fusidic acid and flucloxacillin. The patient recovered with supportive treatment and subsequently tolerated reintroduction of atorvastatin.

Effect of enalapril and losartan on cytokines in patients with stable angina pectoris awaiting coronary artery bypass grafting and their interaction with polymorphisms in the interleukin-6 gene.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may have anti-inflammatory actions, an effect that could explain some of their beneficial effects on cardiovascular events in clinical trials. Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response and provides a convenient model to examine the effects of such agents. Genetic polymorphisms may be important in influencing the expression of cytokines, such as interleukin-6 (IL-6).

Analysis of common IL-6 promoter SNP variants and the AnTn tract in humans and primates and effects on plasma IL-6 levels following coronary artery bypass graft surgery.

Interleukin-6 (IL-6) is a pro-inflammatory cytokine and major mediator of the acute phase response. Single nucleotide polymorphisms within the 5' flanking region (-597G>A, -572G>C and -174G>C) have previously been associated with increased risk of coronary heart disease and influencing transcription of IL-6 both in vitro and in vivo. In addition to these, a polymorphic AnTn tract is also present in the promoter of IL-6.

Human CRP gene polymorphism influences CRP levels: implications for the prediction and pathogenesis of coronary heart disease.

Objective: C-reactive protein (CRP) concentrations are predictive of cardiovascular disease, and levels are heritable, in part. We identified novel polymorphisms in the CRP gene and assessed their influence on CRP level.

Methods And Results: CRP was measured in 250 male army recruits before and after strenuous exercise and perioperatively in 193 coronary artery bypass graft (CABG) patients.

Cortical bone resorption during exercise is interleukin-6 genotype-dependent.

The objective of this study was to examine the relationship between the interleukin-6 (IL-6) -174 G>C promoter polymorphism and exercise-induced femoral cortical bone resorption. Skeletal response to exercise was assessed in 130 male Caucasian army recruits. Five cross-sectional magnetic resonance images of the right femur were obtained before and after a 10-week period of basic physical training, and changes in cross-sectional cortical area were calculated.

A case of spontaneous coronary artery disease regression.

Coronary angiographic trials have demonstrated that lowering cholesterol can slow the progression of atherosclerosis, limit the formation of new lesions and enhance atherosclerotic regression together with reducing the incidence of clinical events (Waters D, 1996). Spontaneous regression of coronary atherosclerotic lesions is rare. We report the case of a patient with a severe within-stent restenotic lesion whose coronary disease spontaneously regressed 12 months after initial diagnosis, allowing for medical treatment of symptoms rather than repeated intervention.

Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response.

Objective: Cyclooxygenase (COX)-2 is a key regulatory enzyme in the synthesis of prostanoids associated with trauma and inflammation. We investigated the COX-2 gene for functional variants that may influence susceptibility to disease.

Methods And Results: The promoter of COX-2 was screened for variants in healthy subjects by use of polymerase chain reaction-based methods.

The effect of the Interleukin-6-174G > C promoter gene polymorphism on endothelial function in healthy volunteers.

Aims: Atherosclerosis is a chronic inflammatory condition, manifest in its early stages by endothelial dysfunction. Interleukin-6 (IL6) plays a key role in driving this process through stimulation of acute phase protein synthesis. We have examined the effect of the IL6 gene -174G > C promoter polymorphism on endothelial function in a group of healthy subjects.

The effect of fibrinogen genotype on fibrinogen levels after strenuous physical exercise.

We have examined the effect of two beta-fibrinogen gene promoter polymorphisms (-455G>A and -854G>A) on the fibrinogen response to severe exercise in a group of male army recruits undergoing basic training. Fibrinogen was measured pre-training and again serially after severe 48 h final military exercise (FME). Out of 884 subjects, 762 completed training of whom 250 were selected for post-FME study.

Impact of angiotensin converting enzyme inhibition on post-coronary artery bypass interleukin 6 release.

Background: Angiotensin 1 converting enzyme (ACE) inhibitors reduce morbidity and mortality after coronary artery bypass graft surgery (CABG). This benefit may result from an anti-inflammatory action.

Objective: To examine the effect of ACE inhibition on interleukin 6 (IL-6) concentrations after CABG.

Effect of a COL1A1 Sp1 binding site polymorphism on arterial pulse wave velocity: an index of compliance.

-Reduced arterial compliance precedes changes in blood pressure, which may be mediated through alterations in vessel wall matrix composition. We investigated the effect of the collagen type I-alpha1 gene (COL1A1) +2046G>T polymorphism on arterial compliance in healthy individuals. We recruited 489 subjects (251 men and 238 women; mean age, 22.

Interleukin-6 gene -174g>c and -572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery.

Interleukin-6 (IL-6) synthesized in response to diverse stimuli may play an important role in bridging the inflammatory and atherosclerotic processes. The acute-phase response after coronary artery bypass graft surgery (CABG) is associated with the induction and release of cytokines, such as IL-6. We have examined the effect of common polymorphisms in the IL-6 gene promoter (-174G>C, -572G>C, and -597G>A) on IL-6 levels after elective CABG.

Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms.

Background: Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature. In explant culture, aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among aneurysm patients, the circulating concentration of IL-6 appears to be increased.

Methods And Results: We investigated, in 19 patients, whether aneurysm wall was an important source of circulating IL-6.

Prognostic value of negative dobutamine stress echo in women with intermediate probability of coronary artery disease.

Women with an intermediate pretest probability of coronary artery disease represent a significant proportion of patients referred for the investigation of chest pain. Dobutamine stress echocardiography can be used to restratify these patients into a low-risk group without resorting to cardiac catheterization.