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)

Familial hypercholesterolemia is a metabolic disorder inherited as an autosomal dominant trait characterized by an increased plasma low density lipoprotein (LDL) level. It has been demonstrated that the disease is caused by several different mutations in the LDL receptor gene. Although early identification of individuals carrying the defective gene could be useful in reducing the risk of atherosclerosis and myocardial infarction, the available techniques for determining the number of the functional LDL receptor molecules are not sufficiently accurate. The recent isolation of the LDL receptor gene now makes it possible to use restriction fragment length polymorphisms to study the inheritance of the defective allele in families with familial hypercholesterolemia. In the present study, we report the use of a Pvu II restriction fragment length polymorphism to follow the inheritance of familial hypercholesterolemia in a total of 79 patients from 37 different families. This restriction fragment length polymorphism allowed unequivocal diagnosis in 32.5% of the cases. Furthermore, in the Italians studied, the absence of a polymorphic Pvu II cutting site (P1 allele) was found to be strongly associated with familial hypercholesterolemia.
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PMID:Pvu II polymorphism of low density lipoprotein receptor gene and familial hypercholesterolemia. Study of Italians. 290 55

Familial hypercholesterolemia is characterized by an increase in low density lipoprotein (LDL) cholesterol, tendon xanthomata, and premature atherosclerosis. In homozygotes, phenotypic expression of the disorder is dominated by genotypic variation at the LDL-receptor gene locus, with other influences, like gender, exerting relatively little effect. In contrast, phenotypic variation in heterozygotes is influenced not only by the nature of the underlying gene mutation but also by gender, diet, and other forms of genetic polymorphism, including the apolipoprotein E genotype.
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PMID:Genotypic and phenotypic variation in familial hypercholesterolemia. 291 34

Three males, aged 15, 22, and 25 years, have been followed for Familial hypercholesterolemia (FH) from 1968 and 1976 onward, being treated by plasmapheresis for 2 to 5 years continuously, at 1- to 2-week intervals. Whereas two patients have been continuously treated to date, the third discontinued plasma exchange after 4 years and has been reevaluated 6 years later. Discontinuation of plasma exchange led to progression of atherosclerosis of the carotid arteries documented by duplex scan, whereas one patient exhibited marked regression of former impressive soft plaque-formation and one patient showed no significant change. Two-dimensional computer-analysis suggested a reduction of plaque mass of up to 45% in one patient.
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PMID:Changes of atherosclerosis of the carotid arteries due to severe familial hypercholesterolemia following long-term plasmapheresis, assessed by duplex scan. 313 70

Patients with heterozygous and homozygous Familial Hypercholesterolemia exhibit a high incidence of premature coronary heart disease, presumably due to atheromatous plaque-formation in the coronary arteries. Clinical symptoms develop when the disease has progressed to more severe stages of atherosclerosis. Aim of our study was to visualize and document early atheromatous lesions in the carotid arteries of asymptomatic patients with familial hypercholesterolemia under 30 years of age by Duplex-scan. Of 44 patients, 70% had detectable carotid plaques, while only 12% of the controls were affected. All patients with severe carotid disease had serum cholesterol levels above 350 mg/dl. In the age group 2-20 years, 66% of the patients exhibited plaques. Only 6% of the FH patients 21-30 years had normal carotid arteries. We conclude that the process of atheromatous plaque formation in patients with FH starts early in life, severity of atherosclerosis being a function of both extent and duration of hypercholesterolemia. Duplex-scan examination of the carotid arteries is efficient and precise non-invasive method suitable to visualize this process and, by measuring regression, monitor the efficacy of therapeutic measures.
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PMID:Atherosclerosis of the carotid arteries in young patients with familial hypercholesterolemia. 327 55

The reduction of elevated low density lipoprotein (LDL) cholesterol concentrations in patients with Type II hyperlipoproteinemia leads to improved cardiovascular morbidity and mortality. Two agents which may be of value in treating hypercholesterolemia are mevinolin and neomycin. Since these drugs lower cholesterol levels through complementary mechanisms, we evaluated the effects of mevinolin and combined mevinolin-neomycin treatment on plasma lipoprotein concentrations in 21 type II hyperlipoproteinemic patients. Mevinolin reduced total and LDL cholesterol concentrations by 24% and 31% respectively (P less than 0.001) and 81% of the patients reduced their LDL cholesterol levels to less than 200 mg/dl. Although the addition of neomycin to mevinolin treatment further lowered total (5%) and LDL (4%) cholesterol concentrations, it also reduced HDL cholesterol levels (19%) (P less than 0.05). Therefore mevinolin normalizes the plasma lipid concentrations in patients with type II hyperlipoproteinemia and combined mevinolin and neomycin treatment offers no advantage over mevinolin-only therapy. In addition, these findings emphasize the importance of determining the HDL cholesterol level to fully evaluate the effects of hypolipidemic therapy.
Atherosclerosis 1986 Jun
PMID:The effects of mevinolin and neomycin alone and in combination on plasma lipid and lipoprotein concentrations in type II hyperlipoproteinemia. 352 86

The long-term effect of specific LDL plasma immunabsorption on the course of coronary arteriosclerosis was tested in ten patients with familial hypercholesteremia type IIa (seven females, three males; age range 15-57 years). Available were ECG, bicycle ergometry, hemodynamic and angiographic data. These tests were repeated seriatim in the course of the LDL immunabsorption. It was found that exercise tolerance markedly increased, ischemic ST-changes became less marked and the initial hemodynamic parameters remained unchanged. The morphology of the coronary arteries was influenced lastingly: among 22 stenoses only one progressed, there was no further progression in 11 stenoses and regression in ten. When there was generalized arteriosclerosis, progression occurred in two of 79 coronary artery segments, progression was arrested in 56 and regression was noted in 21 of 79 segments. These results demonstrate that specific LDL plasma immunabsorption for the elimination of LDL cholesterol favorably influences the course of coronary arteriosclerosis in patients with familial hypercholeremia type IIa. The findings support the lipid theory of atherosclerosis and coronary arteriosclerosis, at least in this special group of patients.
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PMID:[Regression of coronary sclerosis in familial hypercholesterolemia IIa by specific LDL apheresis]. 353 86

Familial hypercholesterolaemia is caused by genetic defects in the cellular metabolism of cholesterol (C) and is characterized by high levels of low-density lipoproteins (LDL) and premature atherosclerosis. The C is carried in the plasma mainly as an LDL-C complex, and removal of the latter from plasma is highly desirable. This task can be achieved by selective haemoperfusion (HP), thereby eliminating the need for plasmapheresis. Agarose beads (2 per cent agarose, 0.85 to 1.4 mm in diameter) were prepared, and crosslinked with epichlorohydrin. Heparin and/or ethanolamine were subsequently attached. The beads thus obtained were found to be suitable for the removal of LDL-C from the whole blood of hypercholesterolaemic rabbits, using a simple HP technique. A single two-hour HP treatment with a 40 ml column packed with active agarose beads resulted in a 30 per cent decrease in the C plasma level in the experimental animals. Our previous, in vitro, studies with the plasma of hypercholesterolaemic patients showed a high selectivity of the beads for LDL. Yet when used with hypercholesterolaemic rabbits, a relatively high amount of HDL was also removed from the blood. This can be attributed to a significant difference between the structure of human hypercholesterolaemic lipoproteins and that of rabbits. Upon treatment of blood using the active agarose beads, no abnormalities in plasma and blood composition were detected, except for some prolongation of PT. It is to be hoped that this new system will replace the presently used and highly expensive plasmapheresis.
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PMID:Cholesterol removal by haemoperfusion of whole blood in vivo. 356 Oct 33

Cholesteryl ester storage disease, caused by the loss of lysosomal acid ester hydrolase (EC 3.1.1.13), has been previously associated with hyperlipidemia and premature atherosclerosis. We identified a 23-month-old female with cholesteryl ester storage disease and characterized the plasma lipids and lipoproteins in the proband and her family. These studies illustrate several important points about this disease. First, a high index of suspicion is required to diagnose this disease since the major physical manifestation of the disorder, mild hepatomegaly, is subtle. Second, the Type II hyperlipoproteinemia in the proband is paralleled by a reduction in the concentration of high density lipoproteins. Third, analysis of the plasma lipids and lipoproteins in family members revealed both Type II and Type IV hyperlipoproteinemia with an inheritance pattern similar to that of familial combined hyperlipoproteinemia. Fourth, the parents and brother of this patient had 50% normal fibroblast acid ester hydrolase activity. These results raise the possibility that deficiency of the lysosomal acid ester hydrolase may be linked to familial combined hyperlipoproteinemia and that this enzyme deficiency may be more common than previously appreciated.
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PMID:Characterization of plasma lipids and lipoproteins in cholesteryl ester storage disease. 399 99

Lipid metabolism was studied in 312 males and females of young, middle, elderly and senile ages with dyscirculatory Stage I and II encephalopathy induced by atherosclerosis, arterial hypertension, or their combination. The control group was composed of 216 clinically healthy age-matched subjects. Marked hyperlipidemic shifts in the form of hypertriglyceridemia (HTG), hypercholesterolemia (HC) and hyperbetalipoproteinemia (HBL) were found in patients of both sexes under 45 years of age: HC and marked HTG were significantly more frequent in males. In middle-aged patients marked HTG was more common in males and HC in females. Elderly and senile patients as compared with young and middle-aged ones were characterized by a low cholesterol coefficient of atherogenicity and high levels of high density lipoproteins with antiatherogenic action. The most frequent type of hyperlipidemias in patients of all age groups was IIa, Types IIb and IV were observed less commonly.
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PMID:[Features of lipid metabolism in patients of different sexes and ages with dyscirculatory encephalopathy]. 407 26

Familial hypercholesterolaemia (FH) is a dominantly inherited error of metabolism characterised by a raised plasma low-density lipoprotein (LDL) concentration, xanthomas of skin and tendons, and a tendency to premature heart disease due to atherosclerosis of the coronary arteries. The clinical and biochemical abnormalities are more marked in homozygotes than in heterozygotes. Other biochemical changes include an increased concentration of very-low-density lipoprotein (VLDL) remnants and of a minor subfraction of high-density lipoproteins. Measurement of plasma lipoprotein turnover shows reduced fractional rates of catabolism of LDL and VLDL remnants, and increased production of LDL. Similar abnormalities are found in Watanabe rabbits, an inbred strain carrying a mutation similar to that responsible for FH. Cultured cells from human and animal tissues express surface receptors with high binding affinity for LDL. Binding of LDL to LDL receptors is followed by endocytosis and lysosomal digestion of the lipoprotein. Cultured cells from FH heterozygotes express only half the normal number of LDL receptors; those from homozygotes have little or no receptor activity and are therefore unable to degrade significant amounts of LDL by the LDL-receptor pathway. The LDL receptor has been isolated from cell membranes; it has a molecular weight of about 160 kd. Several different mutant forms of the receptor have been identified in the cells of FH homozygotes. The LDL-receptor pathway for the catabolism of LDL accounts for at least 1/3 of the total LDL catabolised by normal human subjects in vivo and almost none of that catabolised by FH homozygotes. Deficiency of LDL receptors accounts for the increased plasma concentrations of LDL and VLDL remnants in FH. The increased plasma concentration in these lipoproteins is the cause of deposition of lipid in xanthomas and arterial wall, but the mechanism by which lipoprotein enters the cells in which lipid accumulates is not yet understood.
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PMID:The metabolic basis of familial hypercholesterolemia. 630 34


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