Biomedical subjects

Anna Tavridou

Publications and source records attributed to Anna Tavridou.

5 recordsLinked to original sources

PubMed2006

Pharmacological characterization in vitro of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis.

We investigated the effects of EP2306 and EP2302, two novel 2-biphenylmorpholine derivatives, on squalene synthase activity in rabbit and human liver microsomes, lipid biosynthesis, low-density lipoprotein (LDL) receptor expression and LDL protein uptake as well as apoB secretion in HepG2 cells. Both EP2306 and EP2302 inhibited squalene synthase activity dose-dependently. In rabbit liver microsomes, the IC50 values were 33 microM for EP2306 and 0.6 microM for EP2302 whereas in human liver microsomes, they were 63 microM for EP2306 and 1 microM for EP2302. Both EP2300 compounds inhibited cholesterol production by HepG2 cells dose dependently with IC50 values of 13.3 microM for EP2306 and 3 microM for EP2302. Furthermore, both EP2300 compounds and simvastatin significantly reduced triglyceride synthesis and apoB secretion and increased LDL receptor expression and LDL uptake in HepG2 cells. In summary, we have shown that EP2300 compounds are potent inhibitors of squalene synthase activity in rabbit and human liver microsomes and also they are effective inhibitors of cholesterol and triglyceride biosynthesis in HepG2 cells. These results suggest that EP2306 and EP2302 might prove to be useful for lipid-lowering and treatment of atherosclerosis in vivo.

Animals↗

PubMed2005

Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a common endocrinopathy of women of reproductive age, is associated with the early appearance of multiple risk factors for cardiovascular disease, such as abdominal obesity, dyslipidemia, and diabetes mellitus. However, premature atherosclerosis of the carotid artery has not yet been demonstrated in young women with PCOS. Measurement of carotid intima-media thickness (IMT) is considered an easy and reliable index of subclinical atherosclerosis, which is predictive of subsequent myocardial infarction and stroke. To evaluate the cardiovascular risk of PCOS and the participation of the hyperandrogenemic and metabolic pattern, we measured carotid IMT by B-mode ultrasound as well as hormonal and several cardiovascular disease-associated parameters in 75 young women with PCOS and 55 healthy, age- and body mass index-matched women. The PCOS women had significantly increased carotid IMT (0.58 vs. 0.47 mm, P < 0.001) and abdominal adiposity; higher levels of androgens, insulin, homeostasis model assessment score of insulin sensitivity, and total and low-density lipoprotein-cholesterol; and significantly lower levels of SHBG and high-density lipoprotein-cholesterol. In the studied population (n = 130), PCOS status, age, body mass index, and parental history of coronary heart disease were strong positive predictors of carotid IMT, whereas dehydroepiandrosterone sulfate was a strong negative predictor. In PCOS patients lower delta4-androstenedione and high-density lipoprotein-cholesterol levels were additionally strong positive predictors of carotid IMT, whereas in control women only total cholesterol was the additional positive predictor of carotid IMT. In conclusion, young women with PCOS have an early increase of cardiovascular risk factors and greater carotid IMT, both of which may be responsible for subclinical atherosclerosis. The hyperandrogenemic phenotype of the syndrome may attenuate the consequences of the dysmetabolic phenotype on the vascular wall.

Adolescent↗

PubMed2004

Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) in vitro and in vivo.

The oxidation of low-density lipoprotein (LDL) is an important event in the development of atherosclerosis. In the present study, the antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) were studied. Both compounds inhibited dose-dependently the in vitro oxidation of LDL induced by copper ions. EP2306 and EP2302 increased significantly the lag phase of the oxidation reaction at 0.1 and 10 microM, respectively, whereas they reduced the rate of the reaction at 1 and 10 microM, respectively. This inhibitory effect was not due to a free radical scavenging or copper-chelating activity of EP2300 compounds. Moreover, EP2306 and EP2302 inhibited 12-lipoxygenase activity dose-dependently with IC50 values of 454 and 318 microM, respectively, but had no effect on 15-lipoxygenase activity. In hyperlipidaemic rabbits treated with EP2306 for 4 weeks, there was a decrease in thiobarbituric acid-reactive substance (TBARS) levels and a significant increase in total peroxyl radical-trapping potential (TRAP) levels as compared to control animals. The present data suggest that EP2300 compounds are effective inhibitors of copper-mediated LDL oxidation in vitro. Moreover, EP2306 acts as an antioxidant in hyperlipidaemic rabbits, a property which could be beneficial in reducing atherosclerosis.

Animals↗

PubMed2004

Atorvastatin and simvastatin decrease the uptake of acetylated low-density lipoprotein by human monocytes.

Several lines of evidence indicate that HMG-CoA reductase inhibitors, calcium channel blockers, and angiotensin-converting enzyme inhibitors exert anti-atherogenic effects in vitro and in vivo. In the present study, we determined the effect of members of the above classes of drugs on the uptake of modified low-density lipoprotein (LDL) by U937 cells (human monocytic cell line), a key event in the progression of atherosclerosis. U937 cells were treated with drugs and subsequently the uptake of fluorescent acetylated LDL was assessed by flow cytometry. The HMG-CoA reductase inhibitors, atorvastatin and simvastatin (1-30 mumol/l), but not calcium channel blockers or angiotensin-converting enzyme inhibitors, inhibited the uptake of modified LDL by monocytes. Therefore, atorvastatin and simvastatin may slow down the progression of atherosclerosis by inhibiting the formation of foam cells.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Phosphorylase regulates the association of glycogen synthase with a proteoglycogen substrate in hepatocytes.

Changes in the glucosylation state of the glycogen primer, glycogenin, or its association with glycogen synthase are potential sites for regulation of glycogen synthesis. In this study we found no evidence for hormonal control of the glucosylation state of glycogenin in hepatocytes. However, using a modified glycogen synthase assay that separates the product into acid-soluble (glycogen) and acid-insoluble (proteoglycogen) fractions we found that insulin and glucagon increase and decrease, respectively, the association of glycogen synthase with an acid-insoluble substrate. The latter fraction had a higher affinity for UDP-glucose and accounted for between 5 and 21% of total activity depending on hormonal conditions. Phosphorylase overexpression mimicked the effect of glucagon. It is concluded that phosphorylase activation or overexpression causes dissociation of glycogen synthase from proteoglycogen causing inhibition of initiation of glycogen synthesis.

Animals↗