mevalonic acid/necrosis

Expression of functionally active thrombomodulin (TM) on the luminal surface of endothelial cells is critical for vascular thromboresistance. TM maintains thrombohemorrhagic homeostasis by forming a complex with thrombin, which subsequently loses its procoagulant properties and instead activates

In the present study we analyzed the mechanisms of simvastatin toxicity for the PC3 human prostate cancer cell line. At 10 microM, simvastatin induced principally apoptosis, which was prevented by mevalonic acid but not by cyclosporin A, the inhibitor of calcineurin and mitochondrial permeability

OBJECTIVE Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the synovial environment is characterized by intense immunological activity. Evidence suggests that statins modulate immune functions and may have a beneficial effect on patients with RA. We investigated whether

Plasminogen activator inhibitor 1 (PAI-1) is an important mediator of atherosclerosis and liver fibrosis in insulin resistance. Circulating levels of PAI-1 are elevated in obese individuals, and PAI-1 messenger RNA is significantly higher in the livers of obese type 2 diabetic individuals than in

The role of hepatic free cholesterol (FC) in nonalcoholic steatohepatitis (NASH) is raised up and the intervention with cholesterol synthesis will be a potential therapeutic target. This study investigated the hepatoprotective effect of mevalonic acid pathway inhibition by Zoledronic acid (ZA) on

BACKGROUND Mevalonate kinase deficiency is a metabolic autoinflammatory syndrome caused by mutations in the MVK gene, mevalonate kinase, the key enzyme in the non-sterol isoprenoid biosynthesis pathway. Two phenotypes of mevalonate kinase deficiency are known based on the level of enzymatic

Pravastatin, a hydrophilic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, has been reported to beneficially affect atherogenesis, plaque stability, and transient myocardial ischemia in significant coronary artery disease by influencing lipid metabolism and by intracellular signaling

Statins block de novo synthesis of cholesterol by inhibiting the enzyme, HMG CoA reductase. The product of this reaction, mevalonic acid, is also a precursor of isoprenoids, molecules required for the activation of signalling G-proteins, such as Ras. Signal transduction pathways involving Ras are

OBJECTIVE 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert potent anti-inflammatory effects that are independent of their cholesterol-lowering action. We have investigated the effects of these drugs on cytokine-stimulated CD40 expression in human cultured

OBJECTIVE To describe biochemical findings and the spectrum of mevalonate kinase (MVK) gene mutations as well as an associated TNFRSF1A low-penetrance variant in a series of patients with clinical features of the hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). METHODS The MVK gene was

It has been shown previously that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, such as compactin, lovastatin, and pravastatin, block cholesterol synthesis, suppress lymphocyte functions, and beneficially affect atherogenesis. Recently, it was reported that compactin and

Recent reports have implicated osteoprotegerin (OPG) in cardiovascular disease processes. Endothelial and smooth muscle cells produce OPG and its expression in these cells is upregulated by inflammatory mediators. Statins, which besides their lipid lowering properties have various vasculoprotective

Bisphosphonates have been known to directly inhibit bone resorption and promote apoptosis in mature osteoclasts. Although bisphosphonates have been recognized as the most effective drugs to treat osteoporosis and bone cancer metastasis, the exact effects and mechanism(s) of bisphosphonates on

BACKGROUND 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may modulate cellular inflammatory functions independent of serum cholesterol. We tested the hypothesis that statins decrease respiratory burst activity of human polymorphonuclear neutrophils (PMN) in response

OBJECTIVE We previously reported that 10 mg/day of simvastatin significantly reduced clinical scores of rheumatoid arthritis (RA) in patients with active RA with hypercholesterolemia. We have also reported that a certain pharmacological concentration of simvastatin, i.e., 0.05-0.1 microM, inhibits