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)

Cardiovascular disease and osteoporosis together account for most of the morbidity and mortality in our aging population despite significant improvements in treatment. Recently, converging lines of evidence suggest that these 2 diseases share an etiologic factor--that hyperlipidemia contributes not only to atherosclerotic plaque formation, but also to osteoporosis, following a similar biologic mechanism involving lipid oxidation. In vitro studies indicate that lipid products of oxidation promote osteoblastic differentiation of vascular cells and inhibit such differentiation in bone cells. Ex vivo, in vivo, and clinical studies further suggest that lipid-lowering agents reduce both atherosclerotic calcification and osteoporosis. Whether lipid-lowering agents reduce osteoporosis directly or indirectly through lipid reduction remains controversial.
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PMID:Role of lipids in osteoporosis. 1107 36

Endothelial dysfunction and changes in arterial wall morphology including thickening of the tunica intima, excess synthesis of collagenous matrix (fibroblastic intimal thickening) and permanent or dynamic deposition of lipids (fatty streaks) already occur in childhood or adolescence. Definite atherosclerotic plaques in the carotid arteries usually do not manifest themselves before menopause in women or age 40 in men. Obviously, cumulative (long-term) and excessive exposure of the vessel wall to risk factors is required to overcome highly effective defense mechanisms which have not yet been fully investigated. Initiation and early progression of atherosclerosis rely on conventional vascular risk factors such as hyperlipidemia, hypertension, smoking, severe alcohol consumption and chronic infections. Plaque extension is effectively compensated by a focal widening of the vessel, thereby preventing the development of lumen obstruction (vascular remodeling). For stenosis to emerge conventional plaques must convert to complicated plaques characterized by plaque rupture and consecutive atherothrombosis. This process usually starts with small- to medium-sized plaques. Potential determinants of plaque rupture are the composition of the lesion (large lipid-rich core), damage of the fibrous cap (destabilization by chronic inflammation) and hemodynamic stress. According to pathological observations, fissuring of atherosclerotic lesions is a frequent event, while the formation of overlying large thrombi (with progression of stenosis or vessel occlusion) is definitely rare. This conjecture emphasizes the significance of local and systemic thrombus-promoting factors. Actually, the risk profile of advanced atherogenesis in the Bruneck Study was primarily composed of markers of enhanced prothrombotic capacity, attenuated fibrinolysis and clinical conditions known to interfere with coagulation. Almost all subjects with > or =3 procoagulant risk conditions developed carotid stenosis or showed progression of preexisting stenosis during a 5-year period. Increasing insights into the complex biology of arterial atheroma and awareness of the etiologic peculiarities of advanced complicated plaques may serve as a basis for identifying high-risk subjects and for novel vascular prevention strategies with focus on plaque stabilization and antithrombotic/anticoagulant measures.
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PMID:Biology of arterial atheroma. 1109 78

The aim of this review is to present the current knowledge regarding stroke. It will appear in three parts (in part II the pathogenesis, investigations, and prognosis will be presented, while part III will consist of the management and rehabilitation). In the current part (I) the definitions of the clinical picture are presented. These include: amaurosis fugax, vertebrobasilar transient ischemic attack, and stroke (with good recovery, in evolution and complete). The role of the following risk factors is discussed in detail: age, gender, ethnicity, heredity, hypertension, cigarette smoking, hyperlipidemia, diabetes mellitus, obesity, fibrinogen and clotting factors, oral contraceptives, erythrocytosis and hematocrit level, prior cerebrovascular and other diseases, physical inactivity, diet and alcohol consumption, illicit drug use, and genetic predisposition. In particular, regarding the carotid arteries, the following characteristics are analyzed: atheroma, carotid plaque echomorphology, carotid stenosis, presence of ulcer, local variations in surface deformability, pathological characteristics, and dissection. Finally the significance of the cerebral collateral circulation and the conditions predisposing to cardioembolism and to cerebral hemorrhage are presented.
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PMID:Stroke: epidemiology, clinical picture, and risk factors--Part I of III. 1110 23

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

Chitotriosidase, an enzyme involved in the degradation of chitin-containing pathogens with unclear function in humans, has been proposed as a marker of lipid accumulation in macrophages in different lipid-storage diseases, including atherosclerosis. To evaluate (1) if lipid-lowering treatment could modify serum chitotriosidase activity and (2) be useful in monitoring lipid-lowering treatment, we have analyzed this enzyme activity in the participants in the Atozvastatin Versus Bezafibrate in Mixed Hyperlipidemia (ATOMIX) study, a double-blind, comparative, and randomized study comparing the efficacy of atorvastatin and bezafibrate in mixed hyperlipidemia. Because a common genetic deficiency of chitotriosidase modifies serum quitotriosidase activity, this genetic variation was also studied. Seven subjects of 116 (6.03%) were homozygous, and 46 (39.6%) were heterozygous for the defective allele. Mean serum quitotriosidase activity correlated with allele dosage, as it was found to be of 0, 59.8 +/- 52.6 and 81.2 +/- 41.6 nmol/mL/h, in homozygotes for the defective allele, heterozygotes, and homozygotes for the wild-type allele, respectively (P =.0011 for the difference between the last 2 groups). However, this enzyme activity was not found to correlate with lipid levels before and after treatment with either atorvastatin or bezafibrate, and neither with the intensity of the lipid lowering. These results do not support the use of serum chitotriosidase activity as a biologic marker of atherosclerotic plaque modification related to hypolipidemic treatment.
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PMID:Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: effect of the lipid-lowering agents, atorvastatin and bezafibrate. 1128 40

Fluvastatin, the first fully synthetic HMG-CoA reductase inhibitor, has been shown to reduce cholesterol in patients with hyperlipidaemia, to prevent subsequent coronary events in patients with established coronary heart disease, and to alter endothelial function and plaque stability in animal models. Fluvastatin is relatively hydrophilic, compared with the semisynthetic HMG-CoA reductase inhibitors, and, therefore, it is extensively absorbed from the gastrointestinal tract. After absorption, it is nearly completely extracted and metabolised in the liver to 2 hydroxylated metabolites and an N-desisopropyl metabolite, which are excreted in the bile. Approximately 95% of a dose is recovered in the faeces, with 60% of a dose recovered as the 3 metabolites. The 6-hydroxy and N-desisopropyl fluvastatin metabolites are exclusively generated by cytochrome P450 (CYP) 2C9 and do not accumulate in the blood. CYP2C9, CYP3A4, CYP2C8 and CYP2D6 form the 5-hydroxy fluvastatin metabolite. Because of its hydrophilic nature and extensive plasma protein binding, fluvastatin has a small volume of distribution with minimal concentrations in extrahepatic tissues. The pharmacokinetics of fluvastatin are not influenced by renal function, due to its extensive metabolism and biliary excretion; limited data in patients with cirrhosis suggest a 30% reduction in oral clearance. Age and gender do not appear to affect the disposition of fluvastatin. CYP3A4 inhibitors (erythromycin, ketoconazole and itraconazole) have no effect on fluvastatin pharmacokinetics, in contrast to other HMG-CoA reductase inhibitors which are primarily metabolised by CYP3A and are subject to potential drug interactions with CYP3A inhibitors. Coadministration of fluvastatin with gastrointestinal agents such as cholestyramine, and gastric acid regulating agents (H2 receptor antagonists and proton pump inhibitors), significantly alters fluvastatin disposition by decreasing and increasing bioavailability, respectively. The nonspecific CYP inducer rifampicin (rifampin) significantly increases fluvastatin oral clearance. In addition to being a CYP2C9 substrate, fluvastatin demonstrates inhibitory effects on this isoenzyme in vitro and in vivo. In human liver microsomes, fluvastatin significantly inhibits the hydroxylation of 2 CYP2C9 substrates, tolbutamide and diclofenac. The oral clearances of the CYP2C9 substrates diclofenac, tolbutamide, glibenclamide (glyburide) and losartan are reduced by 15 to 25% when coadministered with fluvastatin. These alterations have not been shown to be clinically significant. There are inadequate data evaluating the potential interaction of fluvastatin with warfarin and phenytoin, 2 CYP2C9 substrates with a narrow therapeutic index, and caution is recommended when using fluvastatin with these agents. Fluvastatin does not appear to have a significant effect on other CYP isoenzymes or P-glycoprotein-mediated transport in vivo.
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PMID:Clinical pharmacokinetics of fluvastatin. 1136 92

Considerable evidence of an association between Chlamydia pneumoniae infections and cardiovascular disease has emerged. Animal models using genetically altered mice and hypercholesterolemic rabbits have shown a pathogenic role of C. pneumoniae in accelerating atherosclerotic plaque development. In the present study, we evaluated the effect of chronic C. pneumoniae infection on atherosclerosis in C57BL/6J mice, fed either a regular chow diet or a high fat, high cholesterol diet. Infected animals on an atherogenic diet developed significantly larger lesion areas compared with control mice at 18 weeks (2.5-fold increase; 4177+/-777 vs. 1650+/-808 microm(2); P<0.05) and 24 weeks of age (3.3-fold increase; 14139+/-4147 vs. 4298+/-869 microm(2); P<0.02). This study shows that chronic C. pneumoniae infection accelerates atherosclerotic lesion development in diet induced hypercholesterolemic mice, indicating that C. pneumoniae is a co-risk factor of hyperlipidemia in atherogenesis.
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PMID:Chlamydia pneumoniae infection accelerates hyperlipidemia induced atherosclerotic lesion development in C57BL/6J mice. 1150 Jan 69

Chinese tea and the major health effects include: antimicrobial, anti-ultraviolet radiation, anticancer, lowering blood lipid and glucose, and protecting against coronary heart diseases. In contrast to the extensive studies on the protective effects of tea on cancer, fewer studies on the health effects of tea on cardiovascular diseases (CVD) have been published. This paper summarises the research results on the possible protective effects of tea on CVD available in China. The results from animal studies clearly demonstrated that tea pigments are effective in lowering blood lipid levels and preventing plaque formation in the aorta. However, the evidence of tea pigments in protecting ischemia heart disease (IHD) in humans is less convincing. One large well-designed ecological study reported an inverse correlation between tea drinking and IHD mortality; but the inverse correlation disappeared after controlling possible confounding factors. However, the effects in improving blood lipid levels and rheology biomarkers in hyperlipidemia subjects or CVD patients by tea pigments seem promising. However, these studies were not well-designed, controlled randomized clinical trials. This made the assessment difficult and inconclusive.
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PMID:Candidate foods in the Asia-Pacific region for cardiovascular protection: Oriental tea. 1171 Mar 54

According to contemporary views, the endothelium is not only a barrier separating blood from surrounding tissues, but a dynamic, heterogeneous organ, which possesses many secretory, metabolic and immunologic functions. Endothelial cells produce mediators, which regulate blood flow, influence platelet adhesion and aggregation, coagulation and fibrinolysis and also immunological response. Endothelial dysfunction is defined as an imbalance between vascular relaxing and contracting factors, between procoagulant and anticoagulant mediators or growth-inhibiting and growth-promoting substances. The definition is often confined to dysfunction of the vessel wall tonus control. The endothelial dysfunction frequently proceeds structural changes in vessels, as e.g. atherosclerotic plaque formation, neointima formation and vessel wall remodelling. This dysfunction has been confirmed in systemic hypertension, atherosclerosis, cardiac syndrome X, heart failure, using various invasive and non-invasive techniques. There are pharmacologic and non-pharmacologic methods to modify endothelial functions. It is obligatory to reduce risk factors of atherosclerosis, which lead to endothelial cell damage, i.e. hypertension, hyperlipidemia, cigarette smoking, estrogen deficiency and elevated levels of homocysteine. The role of physical exercise, low-cholesterol diet, discontinuation of smoking is emphasised. Among drugs statins, angiotensin-converting enzyme inhibitors and hormone replacement therapy are considered particularly beneficial. The importance of angiotensin receptor antagonists, endothelin receptor antagonists, L-arginine, growth factors and calcium-channel blockers for the improvement of endothelial function is studied.
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PMID:[Vascular endothelium--function, disorders and clinical modification probes]. 1171 25

Individuals who survive an acute myocardial infarction (MI) have up to a ninefold greater risk of cardiovascular morbidity and mortality compared with the general population. The modification of traditional coronary risk factors, including hypertension, hyperlipidemia, tobacco use, and diabetes mellitus, constitutes one of the cornerstones of management after acute MI. Therapies aimed at reversing the pathophysiologic disorders that lead to endothelial dysfunction, thrombosis, and atherosclerotic plaque instability may improve the prognosis for patients after acute MI. Aggressive risk stratification diagnostic testing can identify patients at the highest risk for adverse events. Prior to hospital discharge, patients should have an evaluation of left ventricular systolic function, an assessment for the risk for residual myocardial ischemia, and a clinical assessment of the risk for serious ventricular arrhythmias. An array of pharmaceutical agents is available for the secondary prevention of MI, including antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors, and statins.
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PMID:Management After Myocardial Infarction. 1179 27


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