Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aim of our study was to assess adherence to the National Cholesterol Education Program Adult-Treatment Panel II (NCEP-ATP II) in patients cared for by General Practitioners (GPs) in an Italian community. The design of the work was cross-sectional cohort study; the base was an unselected cohort of 1,168 patients cared for by GPs and screened at our lipid clinic in 1994-1995 in the Province of Turin (Italy). Blood samples were collected after 12-hr fast to measure plasma levels of total cholesterol, triglycerides, HDL-cholesterol, glucose and thyroid-stimulating hormone (TSH). LDL-cholesterol was calculated using Friedewald's formula. In patients with body mass index (BMI) >30 kg/m2, an oral glucose tolerance test was performed. Blood pressure was measured in all patients, and a baseline ECG or a stress test was performed in those with unknown cardiovascular disease (CVD), then they were classified following the NCEP-ATP II criteria. Primary hyperlipidaemia accounted for 86.9% of the cohort with most patients requiring pharmacological treatment; in 34.4% of the patients, LDL-cholesterol values were > or = 6.46 mmol/l (250 mg/dl) and in 23.7% with established CVD, LDL-cholesterol levels were > or = 5.68 mmol/l (220 mg/dl). In only 7.3% of patients the NCEP treatment goals were achieved, with 1.3% among those in secondary prevention. We observed great discrepancies between clinical practice and international recommendations for the management of hyperlipidaemia.
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PMID:Low adherence of General Practitioners to National Cholesterol Education Program guidelines for the management of hyperlipidaemia. 1110 68

Advanced arterial wall calcification in atherosclerosis imposes a serious rupturing effect on the aorta. However, the mechanism of dystrophic calcification linked to hyperlipidemia, that causes atherosclerosis remains unknown. Emerging morphological and biochemical evidence reveals that calcifiable vesicles may have a role in plaque calcification. To determine whether a high cholesterol diet can induce arterial calcification and produce or activate calcifiable vesicles in aortas, a rabbit model was used. After 2 months of daily high lipid feeding (supplemented with 2% cholesterol and 6% peanut oil), typical atherosclerotic lesions developed. However, the mineral, if present in aortas, was insufficient to be detected by Fourier transform-infrared spectroscopy (FT-IR) or alizarin red staining, indicative of a non-calcifying stage of atherosclerosis. Small segments of thoracic aortas were digested in a crude collagenase solution to release calcifiable vesicles. Vesicles were also isolated from normal aortas as control to consider the possibility that membrane vesicles may be produced by crude collagenase digestion, which could cause the degradation of some cells. Calcifiable vesicles were precipitated at 300,000 x g after subcellular particles were removed by centrifugation at 30,000 x g. Calcifiability of isolated vesicles was then tested using calcifying media containing physiological levels of Ca2+ and Pi and 1 mM ATP. Electron microscopic observations showed that the isolated vesicles were heterogeneous in size and shape and capable of depositing electron dense particles. Fourier transform infrared spectroscopic analysis of the deposited particles revealed the presence of an amorphous mineral phase. The spectroscopic mineral to matrix ratios, related to the amount of mineralization, indicated that vesicles from cholesterol-fed rabbits produced more minerals than control vesicles obtained from the normal aortas. Alizarin red staining for mineral further demonstrated substantially higher calcifiability of the experimental vesicles. A 3-5 h exposure of the vesicles to calcifying media caused significant deposition of 45Ca and 32Pi in a vesicle protein-concentration dependent manner. Similar to previously reported observations with human atherosclerotic aorta vesicles, rabbit vesicles were enriched in ATP-hydrolyzing enzymes including Mg2+- or Ca2+-ATPase and NTP pyrophosphohydrolase that are implicated in normal and pathological calcification. Altogether, these observations suggest that accumulation of the released calcifiable vesicles, as a result of high cholesterol diets, may have a role in dystrophic calcification in hyperlipidemia-related atherosclerosis.
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PMID:Isolation of calcifiable vesicles from aortas of rabbits fed with high cholesterol diets. 1116 22

This article reviews the pharmacological and clinical aspects of glimepiride, the latest second-generation sulfonylurea for treatment of Type 2 diabetes mellitus (DM). Glimepiride therapy ameliorates the relative insulin secretory deficit found in most patients with Type 2 DM. It is a direct insulin secretagogue; indirectly, it also increases insulin secretion in response to fuels such as glucose. Its action to augment insulin secretion requires binding to a high affinity sulfonylurea receptor, which results in closure of ATP-sensitive potassium channels in the beta-cells of the pancreas. The question has been raised whether insulin secretagogues by acting on vascular or myocardial potassium channels may prevent ischaemic preconditioning, a physiological adaptation that could affect the outcome of coronary heart disease, but there is evidence against this concern being applicable to glimepiride. Glimepiride's antihyperglycaemic efficacy is equal to other secretagogues. It has pharmacokinetic properties that make it less prone to cause hypoglycaemia in renal dysfunction than some other insulin secretagogues, particularly glyburide (also known as glibenclamide in Europe). Its convenient once daily dosing may enhance compliance for diabetic patients who often also require medications for other co-morbid conditions, such as hypertension, hyperlipidaemia and cardiac disease. Glimepiride is approved for monotherapy, for combination with metformin and with insulin. Clinically, its reduced risk of hypoglycaemia makes it preferable to some other insulin secretagogues when attempting to achieve recommended glycaemic control (haemoglobin A(1c) (HgbA(1c)) 7%). Using suppertime neutral protamine Hagedorn (NPH) and regular insulin with morning glimepiride in overweight diabetic patients achieves glycaemic goals more quickly than insulin alone and with lower insulin doses.
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PMID:Clinical review of glimepiride. 1133 17

We have studied the effects of chronic treatment with cromakalim (75 ug kg(-1) per day) and glibenclamide (20 mg kg(-1) per day) in alloxan-induced diabetic rats. Injection of alloxan (60 mg kg(-1)/i.v., single dose) produced a significant increase in the blood pressure, bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypothyroidism and depression in left ventricular developed pressure (LVDP). While glibenclamide significantly prevented alloxan-induced hyperglycemia and hypoinsulinaemia, it failed to alter hypertension, bradycardia, hypertriglyceridaemia and hypercholesterolemia. Treatment with cromakalim-prevented hypertension and bradycardia, but not the hyperglycemia or hypoinsulinaemia. Co-administration of cromakalim with glibenclamide antagonized the effect of glibenclamide on these parameters. Cromakalim treatment also prevented alloxan-induced hypercholesterolemia and hypertriglyceridaemia. It also produced a significant increase in serum T(3) and T(4) levels. Glibenclamide did not significantly alter alloxan-induced hypothyroidism. In conclusion our data suggest that cromakalim and glibenclamide produce some metabolic effects that are either not related to K(ATP) channel modulation or may involve different sub-types of potassium channels. Further glibenclamide when combined with cromakalim may not be beneficial in a condition when diabetes mellitus and hypertension co-exits.
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PMID:Effects of chronic treatment with cromakalim and glibenclamide in alloxan-induced diabetic rats. 1222 Sep 47

Hyperlipidemia represents a major risk factor for development of vascular dysfunction and atherosclerosis. Although the unfortunate role of low-density lipoprotein has been clearly demonstrated, the mechanistic pathways through which triglyceride-derived free fatty acids (FFAs) contribute to vascular disorders are not completely understood. Thus, the present study was designed to elucidate the effects of FFAs on cultured endothelial cells. The Ca(2+) signaling, endothelial nitric oxide synthase (eNOS) activity, and production of superoxide anions (.O(2)(-)) were monitored in cells treated with bovine serum albumin-conjugated FFA. FFA-loaded cells showed enhanced intracellular Ca(2+) release in response to ATP, histamine, or the SERCA inhibitor thapsigargin. This effect corresponded to an overall increase in intracellularly stored Ca(2+). In contrast, autacoid-triggered elevation of cytosolic free Ca(2+) concentration was blunted in FFA-loaded cells due to inhibition of capacitative Ca(2+) entry. In agreement with the reduced Ca(2+) signaling, the Ca(2+)-dependent activity of eNOS was reduced under basal conditions and if cells were stimulated with ATP, histamine, or thapsigargin. The attenuated eNOS activity was associated with.O(2)(-) release in FFA-loaded cells. These data indicate that FFAs significantly affect endothelial Ca(2+) signaling, eNOS activity, and.O(2)(-) release and, thus, might contribute to vascular dysfunction in atherogenesis.
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PMID:Free fatty acid overload attenuates Ca2+ signaling and NO production in endothelial cells. 1271 74

A prospective controlled study on the benefits of pharmacists' individualized counseling on drug compliance, cholesterol concentration reduction, attainment of National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) low-density lipoprotein cholesterol (LDL-C) goals, and patient satisfaction was carried out in a private community hospital in Hong Kong. All patients who were newly prescribed with lipid-lowering drugs for primary prevention were included. The patients in the individualized counseling group received "intense" counseling and follow-up of cholesterol concentration by a pharmacist for 3 months. The control group received routine counseling. Fifty patients completed the study (26 in the individualized group, 24 in the control group). Compliance was assessed, and those patients who achieved 75% compliance were defined as compliers. In the individualized group, 76.9% were compliers compared with 41.7% in the control group (p < 0.01). The individualized group achieved 28.3%, 27.7%, and 26.1% reduction in total cholesterol, LDL-C, and triglycerides, respectively, compared with 15.3%, 16.3%, and 10.6% in the control group (p < 0.05 for all). Also in the individualized group, 80.8% achieved the ATP III LDL-C goals compared to 58.3% in the control group (p < 0.05). Of patients in the individualized group, 85% felt that the pharmacist counseling service could improve their disease management. The study demonstrated that pharmacists' individualized counseling, together with the assessment of cholesterol concentrations, had positive impacts on the management of hyperlipidemia, including improved drug compliance, better treatment endpoints, and patient satisfaction.
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PMID:Benefits of individualized counseling by the pharmacist on the treatment outcomes of hyperlipidemia in Hong Kong. 1514 71

Cardiovascular disease (CVD) in the developed countries continues to grow at an epidemic proportion. There are a significant number of young adults with no clinical evidence of CVD, but who have two or more risk factors that predispose them to CV events and death. Many of these risk factors are modifiable, and by controlling these factors, the CVD burden can be decreased significantly. Recent statistics have shown that, if all major forms of CVD were eliminated, the life expectancy would rise by almost 7 years. Hence it is imperative that primary prevention efforts should be initiated at a young age to avert decades of unattended risk factors. Hyperlipidemia has been linked to CVD almost a century ago. Since then various clinical trials have not only supported this link, but have also shown the CV benefits in aggressively treating patients with hyperlipidemia. In this generation, we have various therapeutic agents that are capable of reducing the elevated lipid levels. With drugs like statins, we are able to reduce the risk of CVD by about 30% and avoid major adverse events. Newer drugs are being researched and introduced in the treatment of hyperlipidemia in humans. These can be used in combination therapy resulting in optimal levels of lipids. The new National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATP III) guidelines have come as a wake-up call to clinicians about primary prevention of CVD through strict lipid management and multifaceted risk management approach in the prevention of CVD.
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PMID:Optimal management of hyperlipidemia in primary prevention of cardiovascular disease. 1556 19

Mitochondrial dysfunction contributes to a number of human diseases, such as hyperlipidemia, obesity, and diabetes. The mutation and reduction of mitochondrial DNA (mtDNA) have been suggested as factors in the pathogenesis of diabetes. To elucidate the association of cellular mtDNA content and insulin resistance, we produced L6 GLUT4myc myocytes depleted of mtDNA by long term treatment with ethidium bromide. L6 GLUT4myc cells cultured with 0.2 mug/ml ethidium bromide (termed depleted cells) revealed a marked decrease in cellular mtDNA and ATP content, concomitant with a lack of mRNAs encoded by mtDNA. Interestingly, the mtDNA-depleted cells showed a drastic decrease in basal and insulin-stimulated glucose uptake, indicating that L6 GLUT4myc cells develop impaired glucose utilization and insulin resistance. The repletion of mtDNA normalized basal and insulin-stimulated glucose uptake. The mRNA level and expression of insulin receptor substrate (IRS)-1 associated with insulin signaling were decreased by 76 and 90% in the depleted cells, respectively. The plasma membrane (PM) GLUT4 in the basal state was decreased, and the insulin-stimulated GLUT4 translocation to the PM was drastically reduced by mtDNA depletion. Moreover, insulin-stimulated phosphorylation of IRS-1 and Akt2/protein kinase B were drastically reduced in the depleted cells. Those changes returned to control levels after mtDNA repletion. Taken together, our data suggest that PM GLUT4 content and insulin signal pathway intermediates are modulated by the alteration of cellular mtDNA content, and the reductions in the expression of IRS-1 and insulin-stimulated phosphorylation of IRS-1 and Akt2/protein kinase B are associated with insulin resistance in the mtDNA-depleted L6 GLUT4myc myocytes.
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PMID:Depletion of mitochondrial DNA causes impaired glucose utilization and insulin resistance in L6 GLUT4myc myocytes. 1576 7

Lipoprotein abnormalities are present in a high proportion of renal transplant patients. It is accepted that dyslipidemia is associated with atherosclerosis and in the progression of renal disease. Lipid abnormalities may also play a significant role in the development of chronic allograft nephropathy. Sirolimus was found to have an antiatherosclerotic effect in the apolipoprotein E-knockout mice model of hyperlipidemia through its antiproliferative effects. As lipid-mediated renal injury is important in the pathogenesis of glomerulosclerosis which shares common pathogenic mechanisms with atherosclerosis, in this study we have tested the hypothesis that sirolimus prevents lipid-mediated renal injury through the modulation of cholesterol homeostasis of mesangial cells and its anti-inflammatory effects on macrophages. We demonstrated that sirolimus reduced lipid accumulation, as measured by oil red O staining in human mesangial cells (HMCs). Using real-time PCR, we screened the mRNA expression of lipoprotein receptors. Sirolimus significantly suppressed LDL and VLDL receptors and CD36 gene expression. It also increased cholesterol efflux from HMCs by increasing peroxisome proliferator-activated receptor-alpha (PPARalpha), PPARgamma, liver X receptor-alpha, and ATP binding cassette A1 (ABCA1) gene expression. Sirolimus overrode the suppression of cholesterol efflux and ABCA1 gene expression induced by the inflammatory cytokine IL-1beta. Furthermore, sirolimus significantly inhibited inflammatory cytokines IL-6 and TNF-alpha production in macrophages. These data suggest that sirolimus may prevent cellular cholesterol accumulation even in the presence of hyperlipidemia and inflammation, by regulating both cholesterol homeostasis and inflammatory responses.
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PMID:Effects of sirolimus on mesangial cell cholesterol homeostasis: a novel mechanism for its action against lipid-mediated injury in renal allografts. 1576 38

Lipid abnormalities play an important part in raising the cardiovascular risk in diabetic subjects. The main components of diabetic dyslipidemia are increased plasma triglycerides, low concentration of high-density lipoprotein cholesterol, preponderance of small, dense low-density lipoprotein, and excessive postprandial lipemia. Small, dense low-density lipoprotein, the elevation in remnant triglyceride-rich lipoprotein particles, and the low high-density lipoprotein are the most powerful atherogenic components. The coexistence of these three factors strongly aggravates the lipid accumulation in the arterial wall and the formation of atherosclerotic plaques. The position of diabetes in cardiovascular risk assessment has been recently reviewed in the Harmonized Clinical Guidelines on Prevention of Atherosclerotic Vascular Disease. In general, patients with diabetes carry a high risk for cardiovascular disease, but the absolute risk varies depending on the type of diabetes, age, and population baseline risk. The Adult Treatment Program III (ATP III) and the American Heart Association have designated diabetes as a high-risk condition and recommended intensive risk-factor management. Concerning therapeutic targets, both ATP III and the American Diabetes Association (ADA) guidelines have identified low-density lipoprotein cholesterol as the first priority of lipid lowering, and the optimal level was set at less than 2.6 mmol/L (100 mg/dL). There is strong evidence, coming from landmark secondary prevention studies, that LDL lowering in people with diabetes is associated with significant clinical benefits. The benefits of statin therapy in type 2 diabetics can no longer be questioned. Ongoing clinical trials will help clarify the question of whether increasing high-density lipoprotein cholesterol with fibrates in the presence of low low-density lipoprotein levels (lower than 3.4 mmol/L, or 130 mg/dL) will be more beneficial than statin therapy alone. The new paradigms in risk-reduction therapies for type 2 diabetic subjects are focused on cardiovascular disease prevention, rather than only on glucose or lipid control. Therapeutic lifestyle changes are considered primary therapies for hyperglycemia and coexisting metabolic syndrome, which can be diagnosed in more than half of type 2 diabetes subjects. New perspectives of lipid management in type 2 diabetes should take into account that insulin resistance, increased lipolysis, and overproduction of large, buoyant, very low density lipoprotein particles are at the base of diabetic dyslipidemia. Accordingly, drugs acting in the regulatory steps of very low density lipoprotein assembly should be developed. Activation of peroxisome proliferator activated receptor alpha (PPARalpha), as occurs with fibrates, lowers free fatty acids (FFAs) and triglyceride levels. PPARgamma agonism, as demonstrated by the thiazolidinediones, increases triglyceride lipolysis, FFA transport, and conversion of FFAs to triglycerides. As separate activation of PPARalpha and PPARgamma improves lipid metabolism, the development of new drugs integrating PPARalpha and PPARgamma activity (PPAR-alpha/gamma agonists) is a promising line that may further improve insulin resistance, FFA metabolism, and consequently, atherogenic diabetic dyslipidemia.
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PMID:Statins and diabetes. 1586 14


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