Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoandrogenemia in men and hyperandrogenemia in women are associated with increased risk of coronary artery disease but also with visceral obesity, insulin resistance, low high-density lipoprotein (HDL) cholesterol, elevated triglycerides, low-density lipoprotein (LDL) cholesterol and plasminogen activator inhibitor (PAI-1). These gender differences and confounders render the precise role of endogenous androgens in atherosclerosis unclear. Exogenous androgens, on the other hand, induce both apparently beneficial and deleterious effects on cardiovascular risk factors by decreasing serum levels of HDL-C, PAI-1 (apparently deleterious), Lp(a), fibrinogen, insulin, leptin and visceral fat mass (apparently beneficial) in men as well as women. However, androgen-induced declines in circulating HDL-C should not automatically be assumed to be pro-atherogenic, since it may reflect accelerated reverse cholesterol transport instead.Short-term application of supraphysiological doses of exogenous T can reduce the severity and frequency of angina pectoris and improve the electrocardiographic signs of myocardial ischaemia; long-term effects have not been investigated. Nonetheless, interpretations of the effects of pharmacological doses of androgens on arterial compliance and flow-mediated dilatation in particular must be treated with circumspection also because at physiological concentrations, beneficial, neutral, and detrimental effects on vascular reactivity can be observed.Testosterone exerts 'pro-atherogenic' effects on macrophage function by facilitating the uptake of modified lipoproteins and an 'anti-atherogenic' effect by stimulating efflux of cellular cholesterol to HDL. In the majority of animal experiments, exogenous testosterone exerted neutral or beneficial effects on the development of atherosclerosis. In conclusion, the overall effect of administration of testosterone on cardiovascular-disease risk is difficult to assess because androgens have such an extraordinary array of effects in vivo. When dealing with a complex multifactorial condition such as CAD, it is premature to assume that clinical benefits can be derived from manipulation of the sex steroid milieu - even when these assumptions are based on biologically plausible mechanisms or, indeed, on cross-sectional risk-factor observational data. Neither needs the therapeutic use of testosterone in men be restricted by concerns regarding cardiovascular side effects.
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PMID:Testosterone and atherosclerosis. 1291 31

Patients with rheumatoid arthritis (RA) have a two to five times increased risk of developing premature cardiovascular disease that shortens life expectancy by 5-10 years. Traditional risk factors known to promote and accelerate the progression of atherosclerotic lesions however, are often absent in patients with RA. Many similarities have emerged between the paradigm of inflammation in the pathogenesis of atherosclerosis and the well-established mechanisms of inflammation in the pathogenesis of RA. Hence it is intriguing to speculate that inflammation in RA is not confined to the joints but also present in the vessel wall. Indeed, low-grade inflammation and endothelial dysfunction play pivotal roles in the initiation, progression and propagation of the atherosclerotic process. While the healthy endothelium prevents adhesion of mononuclear cells, the defence mechanisms cease under the influence of cardiovascular risk factors and inflammation and they express adhesion molecules (selectins, vascular adhesion molecule-([VCAM-]1, intercellular adhesion molecule-[ICAM-]1) that promote the adherence of monocytes. This expression is induced by pro-inflammatory cytokines such as interleukin-(IL-)1beta and tumor necrosis factor-(TNF-)alpha, by C-reactive protein (CRP), and CD40/CD40 ligand interactions. As all of these factors are present at increased levels in the systemic circulation in RA, it appears possible that they might impact the endothelium as well. Further similarities include proteolytic enzymes such as matrix metalloproteinases (MMPs) that play a role in joint destruction as well as in destabilization and rupture of vulnerable atherosclerotic plaques. In addition, coagulation factors such as increased levels of tissue factor (TF), van Willebrand factor (vWF) and plasminogen activator inhibitor-(PAI-)1 are important in both, RA and CAD. Endothelial dysfunction has shown to correlate with cardiovascular prognosis in several studies, which indicates its clinical relevance. Endothelial function measurement is performed in the coronary or peripheral circulation (by venous occlusion plethysmography or flow-mediated dilation). Recent studies have demonstrated impaired endothelial function in patients with RA, already at early stages of the disease. Similar results are found in patients with systemic lupus erythematosus (SLE), indicating that inflammation per se may impair altering vascular function. This and more evidence supports the notion that inflammation plays a pivotal role in vascular dysfunction and may by these mechanisms explain at least part of the excess morbidity and mortality observed in RA and SLE. In light of the growing evidence of increased cardiovascular morbidity and mortality mostly independent of traditional risk factors, treatment strategies in RA should not only aim at relieving symptoms and inhibiting joint destruction but should have a beneficial effect on the vasculature to reduce cardiovascular events. Indeed, an improvement in endothelial function in RA was recently demonstrated by anti-TNF-alpha therapy and statins. Whether and to what degree the effects of anti-inflammatory strategies to improve endothelial function, which although clinically well established is still a surrogate, translate into clinical benefit for our patients with rheumatologic diseases needs to be determined in large-scale clinical trials some of which are now already under way.
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PMID:[Rheumatoid arthritis, inflammation, and atherosclerosis]. 1559 72