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)

Hyperleptinemia is considered to be one of predictors of early atherosklerosis complications. This stimulated us to investigate differences between leptinemia in persons with accelerated atherosclerosis and leptinemia in probands without atherosclerosis complications. The study also verified whether leptinemia and its relationship to other anthropometric and biochemical parameters can differ in hypolipemic-treated probands and hypolipemic-untreated individuals. We examined 89 probands with accelerated atherosclerosis. The controls were 20 persons without any signs of accelerated atherosclerosis. Probands with accelerated atherosclerosis had a slight hyperglycemia and were slightly obese, but they did not meet criteria of metabolic cardiovascular syndrome. No significant differences between both groups under study were found in terms of anthropometric and biochemical parameters (BMI, % body fat, glycemia, insulin, C-peptide, intact proinsulin, total proinsulin cholesterol, HDL, triglycerides, LDL, homeostatic model of insulin secretion and resistance). Leptin concentration was not different as well. Stratification into males and females showed that women had a significantly higher leptinemia and fat tissue mass. Other biochemical parameters were similar in both groups. We suppose that in individuals without signs of metabolic syndrome, leptinemia does not belong among predictors of accelerated atherosclerosis. The accelerated atherosclerosis persons were then divided into subgroups according to medication (28 probands--pravastatin Lipostat 20, 15 probands--phenofibrate Lipanthyl 200M, 9 probands--simvastatin Zocor 20, 47 probands--no hypolipemic medication). No significant differences between the groups were found in terms of the analysed anthropometric and biochemical parameters, except leptinemia. The pravastatin-medicated probands had a significantly lower leptinemia (significant at 99% significance level) which was evidently sex-related than other patients. The pravastatin-administered persons showed no correlation between leptinemia and body fat mass (in contrast to other groups where such a correlation was highly statistically significant). These findings can be explained by a still unclear effect of pravastatin on insulin metabolism and on other factors involved in leptin synthesis and elimination. Thus, a new therapeutic effect of pravastatin can be supposed. This may account for a highly favourable effect of pravastatin on reduced manifestations of atherosclerosis complications event at a low LDL cholesterol decrease (particularly in persons with metabolic cardiovascular syndrome).
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PMID:[Serum leptin, early atherosclerosis and hypolipidemia (a new, previously undescribed effect of pravastatin, a hypolipemic agent)]. 1042 91

Hypercholesterolemia is associated with accelerated atherosclerosis in transplant recipients. It has been notoriously difficult to treat pharmacologically due to the complex interactions that occur with lipid-lowering drugs and immunosuppressive therapies. The purpose of the current study was to compare the efficacy and safety of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (lovastatin, 20 mg/d) with a fibric acid derivative (gemfibrozil, 600 mg twice a day). We used a randomized, crossover design in 18 solid organ transplant recipients who followed the National Cholesterol Education Program Adult Treatment Guidelines diet for 8 weeks and had persistent elevations of total cholesterol (>240 mg/dL). Each patient received each therapy for a minimum of 8 weeks (mean 14.2 +/- 2.4, range 8-20 weeks). The participants had stable allograft function and were treated with a standard immunosuppressive regimen containing cyclosporine, prednisone, and azathioprine. Lovastatin therapy reduced the mean total cholesterol by 15.5% (271.9 mg/dL to 229.9 mg/dL; p = 0.02) and the mean low-density lipoprotein (LDL) cholesterol by 22.7% (178.2 mg/dL to 137.8 mg/dL; p = 0.07). There were no significant changes in high-density lipoprotein (HDL) cholesterol or triglycerides. Conversely, when these same patients were treated with gemfibrozil, the mean total cholesterol decreased by 7.9% (271.9 mg/dL to 250.5 mg/dL; p = NS) and the LDL cholesterol decreased by 5.1% (178.2 mg/dL to 169.1 mg/dL; p = NS). In addition, the mean triglyceride concentration decreased significantly by 46.1% (234.0 mg/dL to 126.3 mg/dL; p = 0.002) and the mean HDL cholesterol increased 15.4% (48.8 mg/dL to 56.3 mg/dL; p = 0.09). In all patients, the serum creatinine, hepatocellular enzymes, and creatinine phosphokinase remained stable. Lovastatin was discontinued in three patients for myalgias, one patient with unexplained anemia, and one patient with parasthesias. These results suggest that lovastatin and gemfibrozil are both safe and efficacious in transplant patients. However, neither therapy alone completely corrects abnormalities of high LDL cholesterol and low HDL cholesterol in transplant recipients.
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PMID:A crossover comparison of the efficacy and safety of lovastatin and gemfibrozil in the treatment of hyperlipidemic organ transplant recipients. 1042 97

We investigated the influence of lovastatin, simvastatin and pravastatin on proliferation and viability of vascular smooth muscle cells (SMC) in vitro and studied the effects of lovastatin on a mouse SMC line transgenic for a temperature-sensitive mutant of SV40 large T antigen (TAg), known to inhibit the function of p53 and pRb family members. We found that lovastatin and simvastatin inhibited cell proliferation by provoking G0/G1 phase arrest with concomitant depression of the proliferation antigen Ki-67/MIB-1. Lovastatin at high concentrations of 20 micromol/l caused cell death in the presence of serum but not under serum starved conditions, which was verified on the basis of increased DNA strand breaks, decreased DNA content and morphological alterations seen by electron microscopy. Cell death was also found for simvastatin, whereas pravastatin did not exhibit antiproliferative or cytotoxic effects. Mouse SMC transgenic for TAg did not show any impaired sensitivity to the antiproliferative and cell death inducing effect of lovastatin, but both effects could be antagonized by the supplementation of mevalonate. The data indicate that antiproliferative and cytotoxic effects of lovastatin are caused by the using up of products of mevalonate metabolism and do not require the presence of p53 or pRb.
Atherosclerosis 2000 Jun
PMID:Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture. 1085 25

The beneficial effects of statins on the reduction of cardiovascular events has been partly attributed to their anti-inflammatory properties. In the complex of the different pathogenetic events leading to atherosclerosis, recent data suggest a central role of monocyte chemotactic protein-1 (MCP-1), because mice knock-out for MCP-1 or its receptor CC-chemokine receptor 2 were considerably resistant to plaque formation. In this study we investigated the effect of different statins on in vitro and in vivo production of MCP-1. Lovastatin and simvastatin caused a dose-dependent inhibition of MCP-1 production in peripheral blood mononuclear cells exposed to lipopolysaccharide or inactivated Streptococcus hemoliticus and in human endothelial cells exposed to interleukin-1beta. The addition of mevalonate overrode the inhibitory effect of statins indicating that mevalonate-derived products are important for chemokine production. The in vivo anti-inflammatory effect of statins was investigated using the mouse air-pouch model of local inflammation. Lovastatin and pravastatin were orally administered to mice according to a treatment schedule that significantly inhibited the hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity without affecting total blood cholesterol. At the dose of 10 mg/kg, lovastatin and pravastatin reduced by approximately 50% the lipopolysaccharide-induced leukocytes recruitment and the exudate MCP-1 production. In conclusion, statins, by inhibiting mevalonate-derived products, reduced both in vitro and in vivo the production of chemokines involved in leukocyte migration, and this effect is unrelated to their cholesterol-lowering action.
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PMID:Inhibition of monocyte chemotactic protein-1 synthesis by statins. 1090 55

Oxidized low density lipoprotein (LDL) has a major impact in the development of atherosclerosis. Risk for oxidative modification of LDL is usually determined indirectly by measuring the capability of LDL to resist radical insult. We compared three different methods quantifying the antioxidative capacity of LDL ex vivo in dyslipidemic patients with coronary heart disease. Plasma samples were obtained from two double-blinded cross-over trials. The duration of all interventions (placebo, lovastatin 60 mg/day, RRR-alpha-tocopherol 300 mg/day and lovastatin + RRR-alpha-tocopherol combined) was 6 weeks. The total radical capturing capacity of LDL (TRAP) in plasma was determined using 2,2-azo-bis(2,4-dimethyl-valeronitrile) (AMVN) -induced oxidation, and measuring the extinction time of chemiluminescence. TRAP was compared to the variables characterizing formation of conjugated dienes in copper-induced oxidation. Also the initial concentrations and consumption times of reduced alpha-tocopherol (alpha-TOH) and ubiquinol in AMVN-induced oxidation were determined. Repeatability of TRAP was comparable to that of the lag time in conjugated diene formation. Coefficient of variation within TRAP assay was 4.4% and between TRAP assays 5.9%. Tocopherol supplementation produced statistically significant changes in all antioxidant variables except those related to LDL ubiquinol. TRAP increased by 57%, the lag time in conjugated diene formation by 34% and consumption time of alpha-TOH by 88%. When data of all interventions were included in the analyses, TRAP correlated with the lag time (r = 0.75, p < 10(-6)), with LDL alpha-TOH (r = 0.50, p < 0.001) and with the consumption time of alpha-TOH (r = 0.58, p < 0.0001). In the baseline data, the associations between different antioxidant variables were weaker. TRAP correlated with the lag time (r = 0.55, p < 0.001) and alpha-TOH consumption time (r = 0.48, p < 0.05), and inversely with apolipoprotein Al (r = -0.51, p < 0.05). Lag time at the baseline did not correlate with ubiquinol or tocopherol parameters, or with any plasma lipid or lipoprotein levels analyzed. Lovastatin treatment did not significantly affect the antioxidant capacity of LDL. In conclusion, TRAP reflects slightly different properties of LDL compared to the lag time. Thus, LDL TRAP assay may complement the other methods used to quantify the antioxidant capacity of LDL. However, TRAP and the lag time react similarly to vitamin E supplementation.
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PMID:Comparison of LDL trap assay to other tests of antioxidant capacity; effect of vitamin E and lovastatin treatment. 1120 90

Freshly solubilized A beta peptides synergistically increase the magnitude of the constriction induced by endothelin-1 (ET-1), via the activation of a pro-inflammatory pathway. We report that mevinolin and mevastatin, two inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase are able to completely abolish the vasoactive properties of A beta in rat aortae. Mevinolin also appears to oppose the increased vascular reactivity to ET-1 induced by interleukin 1-beta and phospholipase A(2) suggesting that statins display some anti-inflammatory properties. We show that freshly solubilized A beta stimulates prostaglandin E(2) and F(2 alpha) production (by 6 and 3.6 times, respectively) in isolated rat aortae and that mevinolin completely antagonizes this effect confirming the anti-inflammatory action of mevinolin ex vivo in rat aortae. In addition, we observed that A beta vasoactivity is not mediated nor modulated by mevalonic acid suggesting that the anti-inflammatory action of the statins are not related to an inhibition of HMG-CoA reductase activity. Differentiated human neuroblastoma cells (IMR32) were used to assess the neurotoxic effect of pre-aggregated A beta by quantifying the release of lactate dehydrogenase (LDH) in the cell culture medium. A beta appears to enhance LDH release by 30% in IMR32 cells, an effect that can be completely opposed by mevastatin. Taken together these data show that statins can antagonize the effect of A beta in different assays and provide new clues to understand the prophylactic action of the statins against Alzheimer's disease.
Atherosclerosis 2002 Apr
PMID:Statins inhibit A beta-neurotoxicity in vitro and A beta-induced vasoconstriction and inflammation in rat aortae. 1188 11

Combined hyperlipidemia (coincident present hypercholesterolemia and hypertriglyceridemia) may contribute to the development of atherosclerosis and coronary artery disease by increasing of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as marker of CAMs. The aim of this study was to determine whether combined hyperlipidemia in overweight adults without clinical evidence of cardiovascular disease, diabetes mellitus or hypertension is associated with increased expression of CAMs. We examined the levels of soluble cell adhesion molecules (sICAM-1, sE-Selectin and sP-Selectin) in blood plasma of overweight adults (n = 36), mean of BMI 27.08 +/- 4.12 kg/m2 with combined hyperlipidemia, with total cholesterol (TC) 7.27 +/- 1.50 mmol/l, LDL cholesterol 4.89 +/- 1.35 mmol/l, HDL cholesterol 1.27 +/- 0.51 mmol/l and triglycerides (TG) 4.08 +/- 2.22 mmol/l before lipid-lowering therapies, and in equal numbers of age, sex and BMI matched controls. Patients with combined hyperlipidemia had significantly higher plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) (298.13 +/- 41.24 ng/ml versus 241.35 +/- 37.48 ng/ml; P < 0.001), sE-Selectin (63.31 +/- 9.48 ng/ml versus 42.16 +/- 14.18 ng/ml; P < 0.001) and sP-Selectin (161.18 +/- 20.85 ng/ml versus 111.54 +/- 26.12 ng/ml; P < 0.001) compared with overweight, non-hyperlipidemic control subjects. Combined hyperlipidemia in adults with overweight is associated with elevated soluble plasma levels of CAMs. We suppose that levels of CAMs in these patients may be determined as a marker for appreciation of their potential atherosclerotic burden.
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PMID:Increasing plasma levels of soluble cell adhesion molecules (sE-Selectin, sP-Selectin and sICAM-1) in overweight adults with combined hyperlipidemia. 1244 98

In the context of the growing complexity of atherosclerosis, LDL-cholesterol has been gradually revealed to be the main aetiological agent. However, the first clinical trials were not convincing, as they failed to demonstrate a significant improvement of coronary mortality. So-called "regression" trials revealed the need to develop clinical trials in which the primary endpoint is coronary events and no longer intermediate criteria such as the course of coronary disease on coronary angiography. Lovastatin, simvastatin and pravastatin were shown to be effective in the prevention of relapses in coronary patients and in the prevention of coronary events in healthy subjects. In 1999, the prescription for coronary patients should almost always include a statin and the prescription in healthy subjects should include a statin when this subject presents a high risk of coronary events in the years to come.
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PMID:[Primary and secondary prevention of coronary disease by statins]. 1255 37

Selectins are carbohydrate-binding molecules that bind to fucosylated and sialylated glycoprotein ligands, and are found on endothelial cells, leukocytes and platelets. They are involved in trafficking of cells of the innate immune system, T lymphocytes and platelets. An absence of selectins or selectin ligands has serious consequences in mice or humans, leading to recurrent bacterial infections and persistent disease. Selectins are involved in constitutive lymphocyte homing, and in chronic and acute inflammation processes, including post-ischemic inflammation in muscle, kidney and heart, skin inflammation, atherosclerosis, glomerulonephritis and lupus erythematosus. Selectin-neutralizing monoclonal antibodies, recombinant soluble P-selectin glycoprotein ligand 1 and small-molecule inhibitors of selectins have been tested in clinical trials on patients with multiple trauma, cardiac indications and pediatric asthma, respectively. Anti-selectin antibodies have also been successfully used in preclinical models to deliver imaging contrast agents and therapeutics to sites of inflammation. Further improvements in the efficiency, availability, specificity and pharmacokinetics of selectin inhibitors, and specialized application routes and schedules, hold promise for therapeutic indications.
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PMID:The role of selectins in inflammation and disease. 1282 15

Long-term effects of Cholestin (Monascus purpureus rice; red yeast rice) on serum lipids and severity of atherosclerosis were examined in rabbits fed for 200 days on a semi-purified diet containing 0.25% cholesterol. Serum total cholesterol was 25 and 40% lower, respectively, in rabbits fed 0.4 or 1.35 g/kg/day of Cholestin (Monascus purpureus rice; red yeast rice) compared to controls. This treatment also lowered serum LDL cholesterol. This 200-day treatment significantly reduced serum triglycerides and atherosclerotic index (ratio of non-HDL-cholesterol to HDL-cholesterol). Although similar reductions of total, LDL-cholesterol and triglycerides were observed, a parallel group of rabbits fed lovastatin (0.0024 g/kg/day) failed to reduce the index significantly. Apolipoprotein A(1) was increased and apolipoprotein B was reduced in all treatment groups. Severity of atherosclerosis was reduced significantly in all treatment groups. The sudanophilic area of involvement was 80.6% in controls, and reduced significantly; to 30.1% on the low dose of Cholestin (Monascus purpureus rice; red yeast rice), and 17.2% on the high dose. Lovastatin reduced severity of lesions by 89% (sudanophilia) and 84% (visual). Visual grading of lesion severity showed reduction by 38% and 68%.
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PMID:Hypolipidemic and anti-atherogenic effects of long-term Cholestin (Monascus purpureus-fermented rice, red yeast rice) in cholesterol fed rabbits. 1287 12


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