Search results for "Hydroxymethylglutaryl CoA Reductases"
showing 9 items of 9 documents
HMG-CoA reductase promotes protein prenylation and therefore is indispensible for T-cell survival.
2017
AbstractStatins are a well-established family of drugs that lower cholesterol levels via the competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). In addition, the pleiotropic anti-inflammatory effects of statins on T cells make them attractive as therapeutic drugs in T-cell-driven autoimmune disorders. Since statins do not exclusively target HMGCR and thus might have varying effects on different cell types, we generated a new mouse strain allowing for the tissue-specific deletion of HMGCR. Deletion of HMGCR expression in T cells led to a severe decrease in their numbers with the remaining cells displaying an activated phenotype, with an increased pro…
Acute Myocardial Infarction and Proinflammatory Gene Variants
2007
We identified four genetic risk sets for acute myocardial infarction (AMI) from information on functional gene variants that favor inflammation or modulate cholesterol metabolism: IL6 -174 G/C, TNF -308 G/A, IL10 -1082 G/A, SERPINA3 -51 G/T, IFNG +874 T/A, HMGCR -911 C/A, and APOE ε2/3/4; 316 patients and 461 healthy subjects, all Italian. Putative risk alleles are shown underlined. The sets were identified using grade-of-membership analysis. Membership scores in the sets are automatically generated for individuals. The ''low intrinsic risk'' set had alleles that downregulate inflammation and cholesterol synthesis (IL6, TNF, ILl0, HMGCR). ''AMI across a broad age range'' carried multiple pr…
Up-regulation of an N-terminal truncated 3-hydroxy-3-methylglutaryl CoA reductase enhances production of essential oils and sterols in transgenic Lav…
2007
Spike lavender (Lavandula latifolia) essential oil is widely used in the perfume, cosmetic, flavouring and pharmaceutical industries. Thus, modifications of yield and composition of this essential oil by genetic engineering should have important scientific and commercial applications. We generated transgenic spike lavender plants expressing the Arabidopsis thaliana HMG1 cDNA, encoding the catalytic domain of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR1S), a key enzyme of the mevalonic acid (MVA) pathway. Transgenic T0 plants accumulated significantly more essential oil constituents as compared to controls (up to 2.1- and 1.8-fold in leaves and flowers, respectively). Enhanced expression …
[The ketogenic diet: an underappreciated therapeutic option?].
2011
Obesity is reaching epidemic proportions in Western countries and is a strong risk factor for cardiovascular disease. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Although there is a common agreement about the concept that exercise and diet are two key factors for the control of body weight, the ideal amount and type of exercise and also the ideal diet for weight control are still under debate. A widely accepted nutritional regime is the Mediterranean diet that has evident health benefits although less attention has been paid to see if the effects are due to other lifestyle factors which may contribute t…
Effects of peroxisome proliferator-activated receptor alpha activation on pathways contributing to cholesterol homeostasis in rat hepatocytes
2004
International audience; Peroxisome proliferator-activated receptor alpha (PPARa) activation by fibrates controls expression of several genes involved in hepatic cholesterol metabolism. Other genes could be indirectly controlled in response to changes in cellular cholesterol availability. To further understand how fibrates may affect cholesterol synthesis, we investigated in parallel the changes in the metabolic pathways contributing to cholesterol homeostasis in liver. Ciprofibrate increased HMG-CoA reductase and FPP synthase mRNA levels in rat hepatocytes, together with cholesterogenesis from [14C] acetate and [3H] mevalonate. The up-regulation observed in fenofibrate- and WY-14,643-treate…
Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids
2005
Dietary vegetable oils and fish oils rich in PUFA (polyunsaturated fatty acids) exert hypocholesterolaemic and hypotriglyceridaemic effects in rodents. The plasma cholesterol-lowering properties of PUFA are due partly to a diminution of cholesterol synthesis and of the activity of the rate-limiting enzyme HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase). To better understand the mechanisms involved, we examined how tuna fish oil and individual n−3 and n−6 PUFA affect the expression of hepatic FPP synthase (farnesyl diphosphate synthase), a SREBP (sterol regulatory element-binding protein) target enzyme that is subject to negative-feedback regulation by sterols, in co-ordination …
The diabetogenic action of statins — mechanisms and clinical implications
2015
Treatment with statins has transformed primary and secondary prevention of cardiovascular disease (CVD), including thrombotic stroke. Evidence-based data demonstrate the benefits and safety of statin therapy and help to guide clinicians in the management of populations at high risk of CVD. Nevertheless, clinical trials, meta-analyses and observational studies highlight a 10-12% increase in new-onset diabetes mellitus (NODM) among patients receiving statins. The risk further increases with intensive therapy and among individuals with known risk factors for NODM. Mechanisms underpinning this effect are not yet fully understood; however, Mendelian randomization studies suggest that they are re…
Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes.
2001
The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activities of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7α-hydroxylase, and ACAT, the major enzymes involved in cholesterol metabolism, were determined in macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and lipoprotein cholesterol contents were also examined. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups had higher serum, LDL-HDL1, and H…
Role of the cyclic AMP-dependent pathway in free radical-induced cholesterol accumulation in vascular smooth muscle cells.
2000
We have previously reported that free radical-treated vascular smooth muscle cells (SMC) lead to cholesterol accumulation in vitro. In the current study, we investigated the effects of oxidative stress on cyclic AMP concentration and cAMP-dependent enzymes involved in cholesterol homeostasis in A7r5 cells. Under our conditions of a mild oxidative stress, namely with no change in cell viability, we found that free radicals, initiated using azobis-amidinopropane dihydrochloride (AAPH), resulted in a dose-dependent decrease in cellular cAMP which was opposed by vitamin E preincubation. Although the addition of adenylate cyclase activators (carbacyclin and forskolin) increased cAMP levels it di…