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)

A Caucasian family of mediterranean origin comprising a patient whose parents were first cousins, his wife and their three children, and his two sisters have been studied. The patient and his two daughters were afflicted with the same corneal opacities and hypoalphalipoproteinaemia. The disease was shown to be transmitted as a non-sex-linked recessive trait. The corneal opacities develop at the end of the second decade of life and consist of numerous minute greyish dots in the entire corneal stroma that give the cornea a misty appearance. Vision slowly deteriorated from 40 years of age. At about 50 years of age, except in one of the two daughters who showed Marfanoid syndrome, the three patients had good general health and no symptoms of atherosclerosis. Biochemical investigations showed hypoalphalipoproteinaemia (with a faint fast-moving HDL band on polyacrylamide gel gradient electrophoresis and small arcs of HDL2 and HDL3 of low mobility determined by agarose gel immunoelectrophoresis), low total cholesterol (3.5-4.9 mmol l-1), slightly decreased cholesteryl ester/total cholesterol ratio (0.52-0.63), extremely low HDL cholesterol (0.20-0.21 mmol l-1), mild hypertriglyceridaemia (1.94-3.80 mmol l-1), and striking deficiency in apo A-I and apo A-II (0.45-0.72, 0.08-0.16 g l-1, respectively). The esterification of HDL cholesterol was low while that of LDL and VLDL was nearly normal. Other laboratory values were normal. The HDL subspecies and major apolipoprotein isoforms have been studied to differentiate FED from Tangier disease, LCAT deficiency, as Apo A-I, A-II, C-II, C-III deficiencies and variants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A 'Fish-eye disease' familial condition with massive corneal opacities and hypoalphalipoproteinaemia: clinical, biochemical and genetic features. 177 23

A study is presented of a 48-year-old female patient and her three siblings with familial hypercholesterolemia. The family members had episodes of cerebral infarction and apparently had atherosclerosis of the internal carotid artery, but no coronary heart disease due to their almost normal level of cholesterol. The laboratory studies of the family members revealed the elevations of serum lipid peroxides, serum lipoprotein(a), leukotriene C4 in blood, the thromboxane B2/6-keto-prostaglandin F1 alpha ratio in plasma and serum hydroxyl radical. Therefore, it is suspected that these factors accelerating atherosclerotic process caused the cerebral infarction. The patient demonstrated corneal opacities, palpebral xanthomas, thickened Achilles tendons, polyneuropathy and the carpal tunnel syndrome. Laboratory studies revealed an elevation in the OKT4/8 ratio, monocyte dysfunction with respect to phagocytosis and chemotaxis, and the presence of the 46XX/45XO mosaic chromosome. Lipid deposits were observed in the Achilles tendon, the transverse carpal ligament, the Schwann's cells and axons of the sural nerve, and in the keratocytes and stroma of the cornea. Following the administration of tocopherol nicotinate and probucol, the patient's serum lipid peroxide normalized and there was improvement in her palpebral xanthomas, thickening of the Achilles tendons and polyneuropathy. We conclude that the lipid deposits in this patient were due to the abnormal oxidative metabolism of low-density lipoprotein and a disturbance of the scavenger pathway due to the monocyte dysfunction.
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PMID:A family of familial hypercholesterolemia with cerebral infarction and without coronary heart disease. An unusual case with corneal opacity, polyneuropathy and carpal tunnel syndrome in the family: therapy with probucol and tocopherol nicotinate. 177 33

Progressive cholesterol deposition frequently occurs in the corneas, tendons, and arteries of those individuals who have hypercholesterolemia. Many investigators have noted histochemical and chemical similarities in the nature of the lipid that accumulates in these tissues. Lipid-soluble dyes have been used to stain hydrophobic lipids such as cholesteryl ester and triglyceride in previous studies of corneal lipid deposits. In this report, deposits of unesterified cholesterol have been detected in the limbal cornea and conjunctiva of hypercholesterolemic rabbits using the fluorescent dye filipin. Whereas, oil red O-stained lipid accumulated both intra- and extracellularly, unesterified cholesterol accumulated extracellularly, similar to its predominant location in tendon xanthoma and atherosclerotic lesions. The source and mechanism by which unesterified cholesterol accumulates in limbal cornea and conjunctiva, tendons, and arteries remains to be determined.
Atherosclerosis 1987 Jan
PMID:Accumulation of unesterified cholesterol in limbal cornea and conjunctiva of rabbits fed a high-cholesterol diet. Detection with filipin. 243 94

In autoimmune hyper- or dislipidemia secondary to a monoclonal antilipoprotein gammapathy, immunoglobulin-lipoprotein (Ig-Lp) complexes are found in the circulating blood. In order to determine their possible significance in common types of hyperlipidemia we compared the Ig-Lp content of sera from 98 healthy blood donors and 155 outpatients from a Lipid Clinic, including 91 cases of hypercholesterolemia (55 familial and 36 non-familial), 15 cases of hypertriglyceridemia, 20 cases of mixed hyperlipidemia and 29 miscellaneous cases. Detection of the Ig-Lp was performed by an ELISA technique with polyclonal affinity purified anti-LDL + HDL as capture antibodies and peroxidase-labeled anti-Ig antibodies specific for IgA, IgG, IgM heavy chains as indicators. Two cases of monoclonal gammapathy (one IgA K and one IgG L) with dislipidemia served as positive controls for the test. IgG, IgA and IgM Lp were found in the sera of the blood donors, in very small quantities when compared with the monoclonal gammapathy cases. All three types of Ig-Lp were also found in the different hyperlipidemic populations studied. When blood donors were compared to hyperlipidemic patients, no difference was observed for IgG Lp. A significant increase in IgM Lp was found in patients with familial hypercholesterolemia (P less than 0.01). An increase in IgA Lp was also found in hypercholesterolemia, familial or not (P less than 0.01), and in patients with corneal arcus (P less than 0.0001), ischaemic disease (P less than 0.01), tendon xanthomas (P less than 0.05) or xanthelasma (P less than 0.05). Furthermore, in a group of 18 paired parents from 9 different families, positive interparent correlations were found for IgM Lp (r = 0.78; P = 0.013) and IgG Lp (r = 0.69; P = 0.038). Therefore IgM Lp may be markers for subpopulations of familial hypercholesterolemia, and IgA Lp markers for the risk of atherosclerotic ischemic disease and deposition of lipids in the cornea. It may be (1) that natural clones of autoanti-lipoprotein antibodies are responsible for the minute quantities of Ig-Lp found in normal people; (2) that the marked development of one of these clones is the cause of autoimmune hyper- or dyslipidemia and xanthomatosis associated with monoclonal gammapathy; (3) that the limited development of a clone produces the Ig-Lp particles found in hypercholesterolemic patients; (4) that there are types of Ig-Lp particles (IgA Lp) that may be harmful for tissues independently of hypercholesterolemia.
Atherosclerosis 1988 Dec
PMID:Immunoglobulin-bound lipoproteins (Ig-Lp) as markers of familial hypercholesterolemia, xanthomatosis and atherosclerosis. 324 Mar 31

The biochemical, clinical, and genetic features were examined in the proband (homozygote) and heterozygotes (n = 17) affected with familial apolipoprotein A-I and C-III deficiency, variant II (previously described as apolipoprotein A-I absence). The proband was a 45-year-old white female with mild corneal opacification and significant three-vessel coronary artery disease (CAD), who died shortly after bypass surgery. Autopsy findings included significant atherosclerosis in the coronary and pulmonary arteries and the abdominal aorta as well as extracellular stromal lipid deposition in the cornea. No reticuloendothelial lipid deposits in the liver, bone marrow, or spleen were noted (unlike Tangier disease). Laboratory features included marked high density lipoprotein (HDL) deficiency and undetectable plasma apolipoproteins (apo) A-I and C-III. The percentage of plasma cholesterol in the unesterified form was normal at 30%. The activity and mass of lecithin:cholesterol acyltransferase (LCAT) were 42% and 36% of normal, respectively, and the cholesterol esterification rate was 43% of normal. Deficiencies of plasma vitamin E and essential fatty acid (linoleic, C18:2) were also noted. Evaluation of plasma lipoproteins and apolipoproteins in 37 kindred members revealed 17 heterozygotes with HDL cholesterol values below the 10th percentile of normal. Of these, all had apoA-I levels more than one standard deviation below the normal mean, and 37.5% had a similar decrease in apoC-III values. Mean (+/- SD) plasma HDL cholesterol, apoA-I, and apoC-III values (mg/dl) in heterozygotes were 54.0%, 62.4%, and 79.2% of normal, respectively. No evidence of CAD was observed in 10 heterozygotes 40 years of age or less; however, CAD was detected in 3 of 7 heterozygotes over 40 years of age, one of whom died at age 56 years of complications of myocardial infarction and stroke. The inheritance pattern in this kindred was autosomal codominant. ApoA-I isolated from a heterozygote had an isoelectric focusing pattern and amino acid composition similar to normal. Utilizing DNA isolated from two obligate heterozygotes, no abnormalities in the apoA-I or apoC-III genes were detected by Southern blot analysis utilizing specific probes following restriction enzyme digestion. The data indicate that familial apolipoprotein A-I and C-III deficiency, variant II, is similar to variant I (described by Norum et al. 1982. N. Engl. J. Med. 306: 1513-1519), but differs at the clinical level (lack of xanthomas), the biochemical level (lack of detectable apoA-I, lower apoA-II level), and at the gene level.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Familial apolipoprotein A-I and C-III deficiency, variant II. 393 6

In order to investigate whether there is a clinical association between Fuchs' endothelial dystrophy of the cornea and atherosclerosis, the prevalence of cardiovascular disease was studied retrospectively in 27 patients with Fuchs' dystrophy and in 27 age- and sex-matched controls. The presence of cardiovascular disease was judged from a patient history of myocardial infarction, angina pectoris or heart insufficiency treated by medicaments and was found in 44% of the group with Fuchs' dystrophy and in 11% of the control group (P less than 0.05). The hypothesis is advanced that there may exist a common endothelial factor of possible significance for the development of corneal endothelial dystrophy, as well as the development of atherosclerotic lesions.
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PMID:Is there an association between Fuchs' endothelial dystrophy and cardiovascular disease? 633 75

.ur current model for cholesterol transport is summarized in Figure 10. In this figure we have put together the various steps in cholesterol transport that were described previously in this review. Under normal conditions, cholesterol metabolism and transport are well regulated. If the transport system is overloaded for a long time, however, hypercholesterolemia caused mainly by increased plasma LDL may develop in several species, including humans. Under such circumstances reverse transport of cholesterol may also fail, giving rise to deposits of cholesterol. Tissue macrophages may be responsible for this lipid accumulation, because receptor-mediated (adsorptive) endocytosis of lipoprotein-associated cholesterol in these cells is not under negative-feedback control. The deposits are mainly found in tissues poorly supplied with blood and lymph: the skin, tendons, the cornea, and arteries. Overload of cholesterol transport may be the result of too much fat and cholesterol in the diet, giving rise to cholesterol-rich lipoproteins from the gut and to increased production of liver (formula; see text) VLDL, which in humans ends up as LDL. In many individuals, however, no hypercholesterolemia is seen, even after eating large amounts of a "western" diet for decades; others may develop increased LDL on a relatively "prudent" diet. Obviously many of the factors and mechanisms in cholesterol transport are influenced by genetic factors. Although studies of several inborn errors of lipid metabolism have given information about some mechanisms, the quantitatively more important differences in genetic patterns, which determine whether or not a western diet will result in hyperlipidemia, are not well known. Perhaps studies of different forms of apoB and apoE and of HDL subgroups and hyper-alpha-lipoproteinemia will explain why certain individuals develop hypercholesterolemia and premature atherosclerosis. All the recent information related to cholesterol metabolism and transport gives rise to new questions. There are many problems of interest for future research: What are the metabolic differences between the apoB produced in the liver and that produced in the gut? To what extent is the protein moiety of LDL modified in the plasma of blood and lymph and in interstitial tissue? Are such modifications important to whether LDL uptake goes through the classic LDL pathway or through the macrophage (i.e., scavenger?) pathway? Are some changes in apoB important for liver recognition of LDL?(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transport of cholesterol. 636 11

Extracts of fresh senile human peripheral cornea with varying degrees of arcus were prepared by soaking minced tissue in buffered saline/EDTA. Apolipoprotein B was, at most, an occasional feature of these extracts; interactions involving glycosaminoglycans were not evident; and the lipid composition, particularly of the cholesterol ester fraction, was also not consistent with a recent origin from plasma components and particularly form low density lipoprotein. Assuming this origin, substantial secondary changes must follow insudation, involving protein loss and lipid reesterification, as is described for lipid deposits forming intracellularly at other sites. The manner of these changes in deposit forming extracellularly in the avascular peripheral cornea is not clear.
Atherosclerosis
PMID:Lipid-protein constituents of human corneal arcus. 728 55

Ophthalmological examination was made for 447 hypercholesterolemic middle-aged Eastern Finnish men participating in the Kuopio Atherosclerosis Prevention Study (KAPS) in order to evaluate the prevalence of corneal arcus, its risk factors, and possible association with atherosclerosis. The degree of atherosclerosis was assessed by ultrasonographic examination of carotid and femoral arteries. Corneal arcus in either eye was observed in 51.4% of the participants. Old age and high LDL cholesterol concentration were associated with the presence of corneal arcus. Corneal arcus had a close relationship with ultrasonographically assessed atherosclerosis.
Cornea 1993 Mar
PMID:Association of corneal arcus with ultrasonographically assessed arterial wall thickness and serum lipids. 850 Mar 21

Schnyder's crystalline corneal dystrophy (SCCD) is an autosomal dominant eye disease characterized by a bilateral clouding of the central cornea, arcus lipoides and/or visible crystalline deposits of cholesterol in the stroma. There is accumulation of phospholipid, unesterified cholesterol and cholesterol ester in the corneal stroma; this is believed to be due to an imbalance in the local factors affecting lipid/cholesterol transport or metabolism. The cellular mechanism of abnormal lipid transport and metabolism in SCCD is of interest due to its potential involvement in atherosclerosis, and its implications for the pathogenesis of cerebrovascular, coronary and peripheral vascular disease as well as corneal opacification. To determine the chromosomal location of the SCCD locus, genome-wide linkage analysis has been performed in two large Swede-Finn kindreds recently identified in central Massachusetts. After analysing 300 microsatellite markers > 90% of the genome was excluded from linkage to the SCCD locus. We now report the chromosomal assignment of the gene for SCCD in both families to be 1p34.1-p36; the maximum multipoint lod-score was 8.48 in the interval between D1S214 and D1S503. From haplotype analysis, the SCCD locus lies in the 16 cM interval between markers D1S2663 and D1S228. Several candidate genes for SCCD have been localized to the 1p34.1-p36 interval.
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PMID:The gene for schnyder's crystalline corneal dystrophy maps to human chromosome 1p34.1-p36. 889 5


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