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)

Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30-300 micrograms/ml), but not native low density lipoproteins (200 micrograms/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 micrograms/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelium evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10(-5) M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease.
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PMID:Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium. 131 34

Cardiovascular disease is a major cause of death. There is evidence that this disease is predicted and its progression influenced by various factors (e.g. hyperlipidaemia). In this review, we consider aspects of platelet structure and function which may explain how this cell type contributes to the pathogenesis of vascular disease. The platelet also contains bioamines (serotonin, 5-HT; histamine) which are potent vasoactive substances. Studies involving patients with peripheral vascular disease (PVD) where abnormalities in platelet function (platelet aggregation and platelet shape change) and in bioamine status (vascular, platelet and plasma bioamine concentrations) are reviewed. We also discuss how platelet activation (in vitro) and plasma lipids influence intraplatelet bioamine status. Finally, we report in vitro evidence of the effect of two drugs prescribed to PVD patients: aspirin and naftidrofuryl. Aspirin is an ineffective inhibitor of 5-HT-induced whole blood platelet aggregation whereas naftidrofuryl is effective in the presence or absence of aspirin. By identifying and altering the factors which contribute to the pathogenesis of atherosclerosis we will be better equipped to prevent, reverse or retard this process.
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PMID:Serotonin, histamine and platelets in vascular disease with special reference to peripheral vascular disease. 134 86

Nephrotic patients with persistent proteinuria also have various lipid abnormalities that may promote atherosclerosis and more rapid progression of renal disease. We aimed to find out whether dietary manipulation can correct the hyperlipidaemia found in these patients. After a baseline control period of 8 weeks on their usual diets, 20 untreated patients with chronic glomerular diseases, stable long-lasting severe proteinuria (5.9 [SD 3.4] g/24 h) and hyperlipidaemia (mean serum cholesterol 8.69 [3.34] mmol/l) ate a vegetarian soy diet for 8 weeks. The diet was low in fat (28% of total calories) and protein (0.71 [0.36] g/kg ideal body weight daily), cholesterol free, and rich in monounsaturated and polyunsaturated fatty acids (polyunsaturated/saturated ratio 2.5) and in fibre (40 g/day). After the diet period the patients resumed their usual diets for 8 weeks (washout period). During the soy-diet period there were significant falls in serum cholesterol (total, low-density lipoprotein, and high-density lipoprotein) and apolipoproteins A and B, but serum triglyceride concentrations did not change. Urinary protein excretion fell significantly. The concentrations of all lipid fractions and the amount of proteinuria tended to return towards baseline values during the washout period. We do not know whether the favourable effect of this dietary manipulation on proteinuria was due to the qualitative or quantitative modifications of dietary protein intake or was a direct consequence of the manipulation of dietary lipid intake.
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PMID:Effect of vegetarian soy diet on hyperlipidaemia in nephrotic syndrome. 134 66

Hyperlipidemia is a major risk factor for atherosclerosis. Early signs of cardiovascular disease can be detected also in asymptomatic patients with hyperlipidemia. Forty-four patients with serum cholesterol greater than 300 mg/dl (7.8 mmol/l) and/or serum triglycerides greater than 500 mg/dl (5.6 mmol/l) and 35 healthy controls had their carotid and iliac arteries examined by echo-Doppler with spectral analysis. Systolic ankle pressure was also measured. A vascular score was calculated: a 0 score was assigned to normal findings and a 1 score for each artery with abnormality at echo-Doppler or Winsor index less than 0.97. The XbaI Restriction Fragment Length Polymorphism of Apo B gene was investigated in all hyperlipidemic patients. Arterial lesions, especially those of internal carotid and iliac arteries, were more frequent (p less than 0.01) in patients with high serum lipids, compared to controls. Patients with lesions were older and had higher serum triglyceride concentrations compared to those without lesions. When divided according to serum triglycerides, patients with concentrations exceeding 200 mg/dl had higher vascular score (p less than 0.02) compared to those with serum triglycerides less than 200 mg/dl. No difference in restriction fragment length polymorphism (XbaI) of Apo B gene was demonstrated in patients with arterial lesions compared to those without lesions. Non-invasive echo-Doppler examination gives useful information on the arterial involvement of hyperlipidemic patients and its use should therefore be implemented, especially when high triglyceride concentrations are present.
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PMID:Early signs of carotid and iliac atherosclerosis in patients with severe hyperlipoproteinemia. 135 42

This study was undertaken to study the effects of hyperlipidemia and hypertension on the coronary circulation and on the myocardium of Watanabe heritable hyperlipidemic (WHHL) rabbits. Surgery to induce hypertension by the one-kidney, one-clip technique was performed on the WHHL rabbits at 3 months of age. At 3 and 6 months after surgery, the right and left coronary arteries and the left ventricle and posterior papillary muscle from normotensive and hypertensive animals were assessed. Atherosclerotic involvement was found at the coronary origin in 94% of the arteries evaluated. Lesions were usually confined to the proximal 1-2 mm of the coronary artery. The prevalence of coronary atherosclerosis in the WHHL rabbit was found to be higher than previously reported in rabbits of the same age. Hypertension-induced muscular and vascular changes such as left ventricular hypertrophy, medial thickening of the arteries, and hyaline arteriolosclerosis were found in most of the hypertensive animals. These changes were rarely seen in the normotensive rabbits. Characteristics of ischemia and cell injury such as eosinophilic fibers, fiber vacuolization, and contraction band necrosis were found more often in hypertensive than in normotensive WHHL rabbits. Confluent areas of severe necrosis indicative of myocardial infarction were not found; myocardial damage was diffuse and involved individual cells and small microscopic areas. This model may be valuable in further studies of coronary artery disease and myocardial injury that result from the combination of hypercholesterolemia and hypertension.
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PMID:Effects of hypertension and hyperlipidemia on the myocardium and coronary vasculature of the WHHL rabbit. 138 26

Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by a deficiency in the receptor that clears low density lipoprotein (LDL) from the serum (reviewed in Ref. 1 and 2). Patients with one abnormal LDL receptor allele have moderate elevations in plasma LDL and suffer premature coronary artery disease (CAD). Approximately 5% of all patients under 45 who have had a myocardial infarction carry this trait. Patients with two abnormal LDL receptor genes (homozygous deficient patients) have severe hypercholesterolemia and life-threatening coronary artery disease in childhood. Strategies for treating patients with FH are directed at lowering the plasma level of LDL. In heterozygotes, this is accomplished through the administration of drugs that stimulate the expression of LDL receptor from the normal allele (2). This therapeutic approach is not effective in the treatment of homozygous deficient patients, especially those that retain less than 2% of residual LDL receptor activity. Partial amelioration of hyperlipidemia has been achieved in some homozygous deficient patients by diverting the portal circulation through a portacaval anastomosis (3) and by chronic plasmapheresis therapy (4). A more direct approach has been to correct the deficiency of hepatic LDL receptor by transplanting a liver that expresses normal levels of LDL receptor. Three patients that survived this procedure normalized their serum LDL-cholesterol (5-9). We have used an authentic animal model for FH, the Watanabe Heritable Hyperlipidemic rabbit (WHHL), to develop gene therapies for the homozygous form of FH (10-13). The WHHL rabbit has a mutation in its LDL receptor gene which renders the receptor completely dysfunctional (12) leading to severe hypercholesterolemia, diffuse atherosclerosis, and premature death. The potential efficacy of gene therapy for FH is supported by a series of studies we have performed in the WHHL rabbit in which we have achieved metabolic improvement (14-18). Liver tissue was removed from WHHL rabbits and used to isolate hepatocytes and establish primary cultures. A functional rabbit LDL receptor gene was transduced into a high proportion of hepatocytes using recombinant retroviruses, and the genetically corrected cells were transplanted into the animal from which they were derived. Transplantation of the genetically corrected, autologous hepatocytes was associated with a 30-40% decrease in serum cholesterol that persisted for the duration of the experiment (4 months, Ref. 18). Recombinant derived LDL receptor RNA was detected in liver for at least 6 months. There was no apparent immunological response to the recombinant derived LDL receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ex vivo gene therapy of familial hypercholesterolemia. 139 Oct 38

The improved longevity of heart transplant recipients demands heightened awareness of the long-term complications of the procedure. Between 1979 and 1990, 232 patients received 241 heart transplants at our institution. Accelerated coronary atherosclerosis occurred in 45 (19%) of the 232 patients, typically appearing within 2 years of transplantation, whereas peripheral vascular disease (PVD) appeared in 23 (10%) of the 232 patients, usually within 3 years of transplantation. In the patients with PVD, 13 had occlusive disease, nine had aneurysms, and one patient suffered a vertebral artery dissection. Accelerated coronary atherosclerosis afflicted 12 (52%) of the 23 patients affected by PVD (p < 0.05) and preceded the development of PVD in all 12. Logistic regression analysis revealed risk factors predictive of the development of PVD after transplantation to be a pretransplant history of ischemic cardiomyopathy and posttransplant hypertension and hypertriglyceridemia (p < 0.05), with the presence of more than one risk factor increasing the probability of development of PVD. Those patients thus identified as at risk should be closely monitored for the development of PVD. Aggressive medical management of hypertension and hyperlipidemia in this subpopulation may forestall or prevent the development of peripheral vascular disease after heart transplantation.
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PMID:Peripheral vascular disease in heart transplant recipients. 140 76

The development of the nephrotic syndrome is associated with a lipid profile characterized by increased total and low density lipoprotein cholesterol. Although total high density lipoprotein (HDL) values may be in the normal range, there is frequently abnormalities of HDL subclasses, with reduction of the mature HDL2 subfraction. While these lipid changes may be considered a risk for atherosclerosis, they revert to normal with remission of the nephrotic syndrome. However, with chronic nephrotic range proteinuria, these abnormalities persist and may also be associated with increased levels of lipoprotein (a), increased levels of very light density lipoprotein and further reductions in HDL. These factors could all contribute to greater risk for atherosclerosis. Although coronary artery disease is frequently seen in patients with end-stage renal disease, and many uncontrolled studies in patients with chronic nephrotic syndrome have suggested an increased prevalence of cardiovascular disease, no prospective studies to evaluate relationship between lipid abnormalities and cardiac disease have been performed in patients with the nephrotic syndrome. Recent experimental data have also suggested a relationship between hyperlipidemia and progressive renal injury. Unfortunately, human epidemiological data are incomplete in correlating lipid changes with renal disease in patients with chronic nephrotic syndrome. No therapeutic trials have tested whether or not pharmacologic interventions will benefit either the cardiac or renal disease that ensues in patients with chronic persistent nephrotic syndrome. Thus, considerably more data are needed to help clarify this important area.
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PMID:Is the aggressive management of hyperlipidemia in nephrotic syndrome mandatory? 140 64

The purpose of this thesis is to investigate the feasibility of using angiographic methods to study, in vivo, fluid mechanical phenomena believed to influence the development and localization of atherosclerotic lesions, in particular, separated flow. This involved developing a method to recognize separated flow by digital analysis of cineangiography films, testing this method both with model measurements and in a clinical material, and a detailed analysis of certain methodological problems. In addition, methods have been developed to measure the tortuosity of arteries, a phenomenon which may, according to fluid mechanical theory, promote the occurrence of separated flow. In a glass model of an arterial bifurcation, a pump generated a pulsatile flow resembling that in large arteries. Using LDV (laser Doppler velocimetry) as a reference method, three velocity profiles in the symmetry plane of the model were recorded. During diastole, extensive separated flow was demonstrated in the larger branch of the bifurcation. The flow was then cineradiographed during injection of contrast medium, and the image sequence was transferred to an image analysis workstation. Treating the image sequence as a set of time-intensity curves, time parameters representing the arrival time of the contrast agent were computed. In the resulting parametric images, zones of delayed filling were identified and found to correspond to the separated flow. Viscosity was measured for seven radiographic contrast media and, as expected, the highest values were found for the largest molecules. For iohexol and ioxaglate, which were studied in detail, a linear relation to temperature and a quadratic relation to concentration were found. Whole-blood viscosity was measured for 5 healthy volunteers at high and low shear rates, before and after mixing with contrast agents in varying proportions. At low shear, viscosity decreased, while at high shear, it increased with increasing contrast concentration. The conclusion was that modern contrast media, despite their higher viscosity, seem to affect blood rheology less than older agents. In a study of the imaging characteristics of the digitization equipment for cinefilms, the resolution proved comparable to that of an entirely digital system, while the noise level was higher. Algorithms for the correction of variations in exposure and geometric distortion are also presented. The method for analysis of cinefilms, tried in the model study, was applied, with slight modifications, to a material of 26 patients with hyperlipidemia and slight or moderate atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiographic methods for the study of fluid mechanical factors in atherogenesis. 141 24

The Program on the Surgical Control of the Hyperlipidemias (POSCH) provided the clearest and the most convincing evidence supporting the beneficial effects of cholesterol lowering in hypercholesterolemic survivors of a myocardial infarction. In POSCH, 78 of the 838 patients (9.3%) were women, with 32 randomized to the diet-control group and 46 to the diet plus partial ileal bypass surgery-intervention group. At 5 years, the mean per cent change from baseline was -23.9% for total plasma cholesterol (p < 0.0001), -36.1% for low-density lipoprotein cholesterol (p < 0.0001), and +8.5% for high-density lipoprotein cholesterol (p = not significant). Because of the small number of women, no statistically significant changes in clinical event rates were observed between the control and the surgery groups. A comparison of 162 coronary arteriography film pairs in the POSCH women, between baseline and 3, 5, 7, and 10 years, consistently showed less disease progression in the surgery group (p = 0.013 for combined assessments of the baseline to the longest follow-up film). Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men, and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate end points for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates, we conclude that the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression. The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women.
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PMID:Women in the POSCH trial. Effects of aggressive cholesterol modification in women with coronary heart disease. The POSCH Group. Program on the Surgical Control of the Hyperlipidemias. 141 88


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