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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied 56 patients affected by primary hypercholesterolemia treated with placebo for 1 month and with simvastatin (20 mg/day) or pravastatin (20 mg/day) for 6 months during a double-blind clinical trial. At 1-month intervals we determined the following parameters in the serum: total and HDL cholesterol, triglycerides, and apolipoprotein A-1 and B. At the same time intervals we also determined the cholesterol and phospholipid concentration, the Na+/K+ ATPase activity, and the fluidity of erythrocyte membranes. Our results demonstrated the following modifications in the erythrocyte membranes during simvastatin and pravastatin treatments: (1) an initial increase in cholesterol concentration and in cholesterol/phospholipid molar ratio, with a significant decrease only after 4 months; (2) a similar behavior of membrane fluidity, with an initial decrease and an elevation after 4 months; (3) an increase in the Na+/K+ ATPase activity only after 4 months. We hypothesize that simvastatin and pravastatin not only inhibit the hepatic synthesis of cholesterol, but also modify the cholesterol exchange between plasma and the erythrocyte membrane.
Exp Mol Pathol 1993 Aug
PMID:Effect of hydroxymethylglutaryl-CoA reductase inhibitors on the functional properties of erythrocyte membranes. 826 65

In this study we examined the effect of cholesterol (Diet 2), cholesterol and fish oil (FO) polyunsaturated acid (Diet 3), and polyunsaturated acid (Diet 4) enriched diets upon the acrosome reaction (AR) of New Zealand White rabbit spermatozoa. Male rabbits fed with cholesterol alone or with FO increased their cholesterol and LDL-cholesterol serum levels after 15 days of diet. Ten semen samples were obtained after 2 months of diet. Our results suggest that hypercholesterolemia and hypertriglyceridemia in male rabbits could produce a decreased capacity of sperm AR after 4 h (0%, 0%, and 60% lower than the control), 6 h (0%, 68%, and 44%), or 8 h (58%, 52% and 32%) of incubation in capacitating medium. Another set of experiments were made with lysophosphatidylcholine (LPC), 80 micrograms/ml, and the same pattern of AR was seen. Nevertheless, the high cholesterol and total lipids (TL) levels in serum did not affect the cholesterol levels in seminal plasma (SP) but affect the SP total lipids. The diminished capacity of rabbit sperm to undergo the AR was not reverted by in vitro incubation with the Shinitsky medium for cholesterol depletion (MDC). These results indirectly suggest that the cholesterol/phospholipid ratio in hypercholesterolemic sperm is similar to that of controls and are in agreement with preliminary studies made in our laboratory that evidenced the same cholesterol/phospholipid ratio in rabbit sperm from hypercholesterolemic animals than from controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1993 Jun
PMID:Cholesterol and polyunsaturated acid enriched diet: effect on kinetics of the acrosome reaction in rabbit spermatozoa. 831 22

To determine whether chronic hypercholesterolemia affects sodium inward currents in cardiac myocytes, whole-cell clamp recordings were made in single cardiac myocytes isolated from normo- and hypercholesterolemic rabbits. Modification of the serum cholesterol was accomplished by feeding ten 3-month-old male New Zealand white rabbits with control diet (group I) and ten with 0.5% cholesterol-enriched diet (group II), for 3 months. The serum cholesterol levels of group II were much higher than those of group I (2042 +/- 231 v 82 +/- 9 mg/dl, P < 0.001). The cholesterol-ester and free cholesterol component of cardiac sarcolemma of group II were also significantly higher than those of group I (26.6 +/- 12.4 v 10.8 +/- 4.5 nmole/dl, P < 0.001, and 50.9 +/- 14.8 v 27.5 +/- 6.2 nmole/dl, P < 0.001, respectively). The cell capacitance of hyperlipidemic myocytes seemed larger than that of normolipidemic ones (157.4 +/- 6.4 pF v 103.6 +/- 3.0 pF, P < 0.05). However, the sodium current density on hypercholesterolemic ventricular sarcolemma was significantly lower than that of normolipidemic sarcolemma. This effect was associated with a leftward shift in the inactivation potential and a slowing of the time course of recovery. In conclusion, hypercholesterolemia has important effects on the sodium inward currents in ventricular myocytes, which may be due to a decrease in current density and an alteration in channel functional state.
J Mol Cell Cardiol 1995 Jun
PMID:The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte. 853 Dec 8

One of the major side-effects of the use of HMG CoA reductase inhibitors for the treatment of hypercholesterolemia is the development of myositis and, in some patients undergoing concomitant immunosuppressive treatment, the development of rhabdomyolysis. Experiments outlined in these studies demonstrate that inhibitors of HMG-CoA reductase activity which differ primary in the substitution of a methyl group for a hydroxyl group have differential effects on both cholesterol levels and cell viability in a striated muscle cell model, the mouse C2-C12 myoblast. Thus, concentrations as high as 200 microM of pravastatin had little effect on total cholesterol level while 25 microM of lovastatin decreased cellular cholesterol by over 90%. Simvastatin and lovastatin decreased viability of C2-C12 myoblasts by nearly 50% at concentrations as low as 1 and 5 microM, respectively, and decreased viability by almost 90% at 10 and 15 microM respectively. However, 300 microM of pravastatin decreased cell viability by less than 50%. The order of potency for the effects on cell viability wassimvastatin>lovastatin>>>pravastatin. The possible relationship between effects on cell viability and the development of myositis is discussed.
J Mol Cell Cardiol 1995 Oct
PMID:Differential sensitivity of C2-C12 striated muscle cells to lovastatin and pravastatin. 857 54

We have identified a rare mutation (T-45C) in the low density lipoprotein (LDL)-receptor gene in a Welsh patient with a clinical diagnosis of heterozygous familial hypercholesterolaemia (FH). The mutation is in the proximal Sp1 binding site in repeat 3 of the 42 bp region of the promoter required for sterol-dependent regulation of transcription, but the substituted nucleotide is not a strongly conserved base in the consensus sequence for Sp1 binding. Normal and mutant promoter fragments (from base -600 to -5) were linked to a luciferase reporter gene, and transient expression in COS cells showed that the mutation reduced transcriptional activity to approximately 43% of normal in the presence, and 25% in the absence of sterols in the medium. Competitive gel-shift mobility assays showed that the mutation reduced the binding affinity for transcription factor Sp1. Analysis of a neutral polymorphism in the LDL-receptor mRNA from the patient's lymphoblasts showed that expression of one allele was reduced. Since Southern blotting of genomic DNA and sequencing of the entire coding region of the LDL-R gene did not reveal any other potential defects, we infer that the T-45 C mutation is the underlying cause of hypercholesterolaemia in the proband.
Hum Mol Genet 1995 Nov
PMID:A mutation (T-45C) in the promoter region of the low-density-lipoprotein (LDL)-receptor gene is associated with a mild clinical phenotype in a patient with heterozygous familial hypercholesterolaemia (FH). 858 90

The effect of dietary MaxEPA (fish oil) supplementation on cholesterol induced hypercholesterolemia in rabbits was investigated. Rabbits were fed 0.1% cholesterol enriched diet for one month and randomly divided into two groups (I and II). Group I was continued on a 0.1% cholesterol rich diet whereas group II in addition to cholesterol supplementation received MaxEPA (2.5 g/kg body weight) per day for a period of two months. B-VLDL-C, LDL-C and total serum peroxide levels (TBARS) were significantly higher in group II animals as compared to group I. No statistical difference was found in the number of hepatic B-VLDL binding sites between group I and II. Microscopic examination of the aorta showed an increase in the number of intimal foam cells in MaxEPA treated group, a result that may be linked to increase in total cholesterol, plasma TBARS and with simultaneous reduced hepatic uptake of B-VLDL.
Biochem Mol Biol Int 1995 Oct
PMID:Effect of MaxEPA (fish oil) on lipoproteins and its receptors in hypercholesterolemic rabbits. 859 89

A brief rapid pacing has been shown to protect rabbit heart against global myocardial ischaemia induced by subsequent longer pacing. We studied whether pacing-induced preconditioning was reproducible in experimental hypercholesterolaemia. In conscious rabbits with an implanted right ventricular electrode and left ventricular polyethylene catheters, pacing of 500 bpm over 20 min induced an intracavitary ST-segment elevation of 3.2 +/- 0.41 mV, shortened ventricular effective refractory period and increased left ventricular end-diastolic pressure from prepacing 105 +/- 3.9 ms and 4.0 +/- 0.93 mmHg to post-pacing 62 +/- 6.4 ms and 27.9 +/- 7.2 mmHg, respectively. A 10-min preconditioning pacing followed by a 5-min interval markedly attenuated these test pacing-induced ischaemic changes. Rabbits were fed a cholesterol-enriched diet over 4, 8 and 12 weeks, responded to a 5- or 10-min pacing with ischaemic changes of the same degree as did controls to a 10- or 20-min pacing, respectively. A 4-week diet elevated total serum cholesterol from 1.7 +/- 0.4 to 24.1 +/- 2.9 mmol/l without apparent atherosclerotic lesions in the thoracic aorta assessed by Oil-Red O staining and planimetry, but it abolished protection induced by a 5-min preconditioning pacing. A 12-week diet increased serum cholesterol and lesion surface area to 26.9 +/- 3.2 mmol/l and 89.6 +/- 6.4%, respectively, and continued to block preconditioning. When these animals were refed normal chow over additional 6 weeks, serum cholesterol level dropped to 2.6 +/- 0.80 mmol/l with no change in atherosclerotic lesions, the preconditioning effect, however, recovered. We conclude that hypercholesterolaemia blocks preconditioning irrespective of the development of atherosclerosis.
J Mol Cell Cardiol 1995 Dec
PMID:The loss of pacing-induced preconditioning in atherosclerotic rabbits: role of hypercholesterolaemia. 882 77

We investigated the relationship between the development of hypercholesterolemia in rabbits and cholesteryl ester transfer protein (CETP) activity secretion by their perfused livers. Two inbred strains of rabbits were compared which differ markedly in their hypercholesterolemic response to dietary cholesterol. Feeding a high-cholesterol (0.3%) diet, increased plasma and liver cholesterol level in the two strains, the increments being 15 mM and 30 mumol/g greater in the hyperresponders, respectively. The high-cholesterol diet caused an about 2-fold increased hepatic secretion of CETP activity, but there was no difference between the two rabbit strains. Feeding a lower amount of dietary cholesterol (0.08%) also caused higher cholesterolemic (2 mM) and hepatocholesterolic (28 mumol/g) responses in hyper- than in hyporesponsive rabbits. The activity of hepatic CETP secretion was not increased by the low-cholesterol diet, and there was no difference between hypo- and hyperresponsive rabbits. Cholesterol feeding increased plasma CETP activity by 90% in both rabbit strains, but there was no difference between the strains. Our combined data suggest that with increasing plasma cholesterol levels hepatic CETP secretion may be increased in a parabolic manner, reaching its maximum rate for before plasma cholesterol concentrations are maximal. There were no differences in hepatic CETP activity secretion of plasma CETP activity levels between the genetically different strains of hypo- and hyperresponsive rabbits.
Comp Biochem Physiol B Biochem Mol Biol 1996 Aug
PMID:CETP activity in liver perfusates and plasma from rabbits hypo- or hyperresponsive to dietary cholesterol. 884 May 15

In this review, a rationale is presented for how hypercholesterolemia, hypertension, diabetes mellitus, end-stage renal disease, renal dialysis, and prolonged stress can all lead to atherosclerosis, ischemic heart disease, and stroke. The data indicate that Mg deficiency caused either by poor diet and/or errors in Mg metabolism may be a missing link between diverse cardiovascular risk factors and atherosclerosis. Data from our laboratories and others indicate that reduction in extracellular and intracellular free Mg ions (Mg2+) can induce an entire array of pathophysiological phenomena known to be important in atherogenesis, that is, vasospasm, increased vascular reactivity, elevation in [Ca2+]i, formation of proinflammatory agents, oxygen radicals, platelet aggegation, reduction in cardiac bioenergetics, cardiac failure, oxidation of lipoproteins, gender-related modulation of endothelial-derived relaxing factor/NO, changes in membrane fatty acid saturation, changes in membrane plasmalogens and N-phospholipids (suggesting changes in intracellular phospholipid signals), and probably transcription factors.
Cell Mol Biol Res 1995
PMID:Magnesium and cardiovascular biology: an important link between cardiovascular risk factors and atherogenesis. 886 81

The standard laboratory diet administered to sand rat (Psammomys obesus) induces the following physiological and immunological changes: hyperglycemia and hypercholesterolemia involving mainly the free fraction of cholesterol, with an elevation of high-density-lipoprotein levels and a decrease in B and T splenic lymphocyte proliferation in the presence of different mitogens PHA-P, Con A and LPS. These results demonstrate the important modification that could be induced in sand rat by the standard laboratory diet as compared with natural diet, and thus the sand rat (P. obesus) appears to be an interesting model for studies on experimental diabetes mellitus.
Cell Mol Biol Res 1995
PMID:Nutritional influences on in vitro splenic lymphocyte proliferation in Psammomys obesus (Rodentia Gerbillidae). 886 85


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