Compared effect of immunosuppressive drugs cyclosporine A and rapamycin on cholesterol homeostasis key enzymes CYP27A1 and HMG-CoA reductase.

Hyperlipidaemia, i.e. increase in total cholesterol and triglycerides, is a common side-effect of the immunosuppressive drugs rapamycin (RAPA) and cyclosporine A (CsA), and is probably related to inhibition of the 27-hydroxylation of cholesterol (acid pathway of bile acid biosynthesis).

Effect of HMGCoA reductase inhibitors on cytochrome P450 expression in endothelial cell line.

Endothelial cells and smooth muscle cells are the major cells that constitute blood vessels, and endothelial cells line the lumen of blood vessels. These 2 types of cells also play an integral role in the regional specialization of vascular structure. On the basis of these observations, we designed our study to investigate the effect of various statins on CYP expression in endothelial cells.

Interaction between CYP1A1 T3801C and AHR G1661A polymorphisms according to smoking status on blood pressure in the Stanislas cohort.

Background: CYP1A1, one of the key enzymes in detoxifying toxic components produced during cigarette smoking, is regulated by aromatic hydrocarbon receptor (AHR). A CYP1A1 T3801C polymorphism, associated with a higher CYP1A1 inducibility and enhanced catalytic activity, has been linked to stroke, triple vessel disease and may, therefore, be associated with blood pressure (BP). The relation of the widely studied G1661A polymorphism of the human AHR gene with BP is unknown.

Pharmacogenomics and cardiovascular drugs: need for integrated biological system with phenotypes and proteomic markers.

Personalized medicine is based on a better knowledge of biological variability, considering the important part due to genetics. When trying to identify involved genes and their products in differential cardiovascular drug responses, a five-step strategy is to be followed: 1) Pharmacokinetic-related genes and phenotypes (2) Pharmacodynamic targets, genes and products (3) Cardiovascular diseases and risks depending on specific or large metabolic cycles (4) Physiological variations of previously identified genes and proteins (5) Environment influences on them. After summarizing the most well-known genes involved in drug metabolism, we will take as example of drugs, the statins, considered as very important drugs from a Public-Health standpoint, but also for economical reasons.

Effect of acute and chronic psychostimulant drugs on redox status, AP-1 activation and pro-enkephalin mRNA in the human astrocyte-like U373 MG cells.

In order to approach the astroglial implication of addictive and neurotoxic processes associated with psychostimulant drug abuse, the effects of amphetamine or cocaine (1-100 microM) on redox status, AP-1 transcription factor and pro-enkephalin, an AP-1 target gene, were investigated in the human astrocyte-like U373 MG cells. We demonstrated an early increase in the generation of radical oxygen species and in the formation of 4-hydroxynonenal-adducts reflecting the pro-oxidant action of both substances. After 1 h or 96 h of treatment, Fos and Jun protein levels were altered and the DNA-binding activity of AP-1 was increased in response to both substances.

[Dyslipidaemia and its management after immunosuppressive treatment].

This article summarises the mechanisms responsible for the hyperlipidaemia observed after immunosuppressive treatment. Much progress has been achieved in the treatment of organ transplantation over the last 10 years, in particular because of the use of new immunosuppressive drugs with less nephrotoxicity. However, hypercholesterolaemia and hypertriglyceridaemia persist among many patients, who are thus more likely to develop cardiovascular diseases.

Cytochromes P450 are differently expressed in normal and varicose human saphenous veins: linkage with varicosis.

The expression of cytochrome P450 (CYP) enzymes and cyclo-oxygenases (COX) was investigated in human saphenous veins by reverse transcription-polymerase chain reaction analysis. Non-varicose veins were obtained from patients undergoing aortocoronary bypass grafting, whereas varicose veins were obtained from patients undergoing stripping removal of varicose saphenous veins. In non-varicose veins, CYP1B1, CYP2C, CYP2E1 and CYP4A11 were detected, whereas CYP2J2, CYP3A5, COX-1 and COX-2 were detected almost exclusively in varicose veins.

Pharmacogenomics of drugs affecting the cardiovascular system.

The variability in drug response originates partly from genetics, with possible consequences for drug efficacy, adverse effects, and toxicity. Until now, pharmacogenetics mainly indicated the best known source of variability, that is, the variability caused by drug metabolism. However, simultaneous progress in the knowledge of biochemical targets of drugs and of the human genome, together with the development of new technologies, revealed many new sources of human genetic variation, e.