Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intra-abdominal fat mass, or central adiposity, and cardiovascular risk are strongly correlated. Adipose tissue is an endocrine organ that secretes hormones and cytokines influencing appetite, energy metabolism, and atherosclerosis. Rimonabant is the first selective blocker of the cannabinoid-1 receptor in development for the treatment of obesity, diabetes mellitus typ 2, and cardiometabolic risk factors. This article provides an review of efficacy of rimonabant the first selective blocker of the cannabinoid-1 receptor.
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PMID:[Positive influence on cardiovascular risk factor by blocking the endocannabinoid system]. 1859 56

Cardiovascular mortality remains the first cause of death worldwide. This high mortality rate is directly associated with the increase of cardiovascular risk factors such as: obesity, hypertension, diabetes and hypercholesterolemia. Current tight management and new pharmacological treatment of cardiovascular risk factors decrease the cardiovascular mortality rate in general population. However, insulin resistance, hypo-adiponectinemia and inflammatory factors persist and are linked with atherosclerosis. Additional therapeutic solutions are needed. Rimonabant, a CB1-blocker brings novel perspective to manage several cardiovascular risk factors. Unfortunately, Rimonabant has been withdrawn from the market. Therefore, it has not been possible to assess in long term its efficacy on cardiovascular mortality.
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PMID:[Nutrition-obesity. Rimonabant and cardiovascular risk factors]. 1921 25

Acyl coenzyme A:cholesterol acyltransferase (ACAT) catalyzes the intracellular synthesis of cholesteryl esters (CE). Both ACAT isoforms, ACAT1 and ACAT2, play key roles in the pathophysiology of atherosclerosis and ACAT inhibition retards atherosclerosis in animal models. Rimonabant, a type 1 cannabinoid receptor (CB1) antagonist, produces anti-atherosclerotic effects in humans and animals by mechanisms which are not completely understood. Rimonabant is structurally similar to two other cannabinoid receptor antagonists, AM251 and SR144528, recently identified as potent inhibitors of ACAT. Therefore, we examined the effects of Rimonabant on ACAT using both in vivo cell-based assays and in vitro cell-free assays. Rimonabant dose-dependently reduced ACAT activity in Raw 264.7 macrophages (IC(50)=2.9+/-0.38 microM) and isolated peritoneal macrophages. Rimonabant inhibited ACAT activity in intact CHO-ACAT1 and CHO-ACAT2 cells and in cell-free assays with approximately equal efficiency (IC(50)=1.5+/-1.2 microM and 2.2+/-1.1 microM for CHO-ACAT1 and CHO-ACAT2, respectively). Consistent with ACAT inhibition, Rimonabant treatment blocked ACAT-dependent processes in macrophages, oxysterol-induced apoptosis and acetylated-LDL induced foam cell formation. From these results we conclude that Rimonabant is an ACAT1/2 dual inhibitor and suggest that some of the atherosclerotic beneficial effects of Rimonabant are, at least partly, due to inhibition of ACAT.
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PMID:Rimonabant is a dual inhibitor of acyl CoA:cholesterol acyltransferases 1 and 2. 2060 60

Biomarkers and imaging trials have often been used as guideposts in the development of drugs for atherosclerosis. This article explores the role of biomarkers and imaging trials in the development of 4 drugs: rimonabant, torcetrapib, ezetimibe, and niacin. Rimonabant, a selective cannabinoid-1 receptor, causes weight loss and exerts favourable effects on lipid biomarkers. An intracoronary ultrasound study showed no effect for the primary but significant benefit for the secondary end point. A large clinical outcomes trial was halted when it became apparent that the drug caused serious psychiatric side effects, including suicide. Torcetrapib, a cholesteryl ester transfer protein inhibitor, lowers low-density lipoprotein (LDL) cholesterol and induces a marked increase in high-density lipoprotein (HDL) cholesterol. However, a large clinical outcomes trial was halted very prematurely due to a 58% increase in all-cause mortality. Neutral imaging studies were reported later. Ezetimibe lowers low density lipoprotein cholesterol but did not reduce carotid intima-media thickness, and there is as yet no clinical trial evidence that it reduces cardiovascular events after a decade on the market. Niacin exerts favourable effects on lipid biomarkers and has shown regression of atherosclerosis in small carotid imaging trials, but did not reduce events in a recent clinical trial that was stopped early due to a lack of efficacy. In summary, favourable effects on lipid biomarkers often do not translate into clinical benefit, and imaging trials, which focus on a narrow measurement of atherosclerosis, are also often not helpful.
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PMID:Utility of biomarkers and imaging in the development of drugs for the treatment of coronary atherosclerosis. 2262 47