Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercholesterolemia impairs arteriolar dilatation, but whether the vascular abnormalities accompanying this condition include large artery function is unknown. We addressed this issue in 13 normotensive subjects with familial hypercholesterolemia (serum cholesterol 401.6 +/- 16.9 mg/dl, mean +/- S.E., FHC) and no evidence of atherosclerotic lesions, in whom radial artery (RA) diameter and blood pressure (BP) were measured beat to beat by an echotracking and a Finapres device, respectively. RA compliance (RAC) was derived from the diameter/BP relationship and expressed over the systo-diastolic BP range, both at baseline and after a 12-min brachial artery occlusion. RAC was expressed also as the area under the RAC/BP curve divided for pulse BP. Measurements included maximal forearm blood flow (plethysmography) and minimal forearm vascular resistance (FVR) which were obtained from the values following the 12-min brachial arterial occlusion. Data were collected before and after 6- and 24-month lipid lowering treatment (simvastatin 40 mg/day). Ten age-matched normotensive normocholesterolemic healthy subjects (N) served as controls. Compared to N, baseline RAC was strikingly reduced in FHC (-53.5%, P < 0.01). After ischemia RAC increased significantly and markedly in N (+38.7, P < 0.01), while only a modest and non-significant increase was observed in FHC. Minimal FVR was markedly higher in FHC than in N (3.5 +/- 0.9 vs 1.6 +/- 0.1 units, P < 0.01). In FHC (7 subjects) RAC remained unchanged after 6 months of lipid lowering treatment, but increased markedly (+55.2%, p < 0.05) when treatment was prolonged to 24 months. Lipid lowering treatment also reduced minimal FVR, the effect being significant both after 6 and after 24 months. No changes in RAC and minimal FVR were seen after 6 months in controls. Thus, in subjects with a marked increase in serum cholesterol due to FHC, not only arteriolar dilatation, but also RAC and distensibility are markedly impaired. This impairment can be favourably affected by an effective lipid lowering treatment of long duration.
Atherosclerosis 1996 Aug 02
PMID:Impaired radial artery compliance in normotensive subjects with familial hypercholesterolemia. 883 Sep 37

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by a multitude of low density lipoprotein receptor (LDL-R) mutations. The purpose of the current investigation was to define the spectrum of mutations causing FH in Israel and determine their relative distribution among diverse origin groups. A total of 193 FH families were recruited in Israel, 54 of them through the MED PED (Make Early Diagnosis Prevent Early Death) FH program. Molecular analysis of the LDL-R using single-strand conformation polymorphism (SSCP) or denaturing gradient gel electrophoresis (DGGE) or both has been completed in 95 index cases. This analysis resulted in the identification of 15 LDL receptor mutations, including 7 novel mutations (del 197, C308G, R385W, splice junction mutation of intron 14, del 328, del 502-505, stop 10, del 165), that were present in 49 index cases (52%). The 15 mutations are mapped to three known functional domains of the receptor (7 in the LDL-binding region, 7 in the epidermal growth factor precursor homology region and 1 in the membrane-spanning region). Screening for the identified mutations in the remaining 98 index cases enabled the molecular diagnosis of 31 additional cases. It is therefore concluded that 80 out of 193 index cases (41%) harbor 1 of the 15 mutations described here. Three mutations-del197 (FH-Lithuania), D147H (FH-Sephardic), and stop660 (Lebanese allele)-were found in a total of 66 index cases (34%); these may be regarded as founder mutations in the three respective origin groups. In conclusion, in Israel molecular heterogeneity at the LDL receptor gene locus reflects the ethnic distribution of its origin groups. The results of the present investigation provide valuable diagnostic tools for a subset of the Israeli patients with FH who are at high risk for atherosclerosis and its complications.
 ...
PMID:Molecular genetics of familial hypercholesterolemia in Israel. 888 79

Familial hypercholesterolemia (FH) can cause early disability and death from premature atherosclerotic cardiovascular disease. Patients homozygous for the disease have very high plasma cholesterol, extensive xanthomatosis, and die from atherosclerosis in childhood or early adulthood. Past attempts to improve the prognosis included removal of cholesterol from the circulation by ileal bypass or biliary diversion. Neither treatment was successful. Direct removal by plasmapheresis of low-density lipoprotein (LDL), the primary carrier of cholesterol in plasma, was first performed on an FH homozygous patient in 1966. The treatment was well tolerated and led to rapid diminution of xanthomas. Other experimental treatments included selective LDL apheresis with monoclonal or polyclonal antibody affinity columns. A method for selective LDL apheresis was developed in 1983 by Armstrong, Seidel, and colleagues based on heparin precipitation of LDL at low pH. This method, called HELP, removes all apolipoprotein B-containing lipoproteins including LDL and lipoprotein (a), as well as some fibrinogen. LDL apheresis by HELP is well tolerated; the incidence of side effects is low, and the treatment has been associated with regression of cardiovascular disease. LDL apheresis, rather than liver transplantation, is the treatment of choice for patients with severe, life-threatening hypercholesterolemia which does not respond to diet and drug therapy.
 ...
PMID:Treatment of hypercholesterolemia with heparin-induced extracorporeal low-density lipoprotein precipitation (HELP). 891 17

Familial hypercholesterolemia was the first genetic disorder recognized to cause myocardial infarction. Patients with homozygous familial hypercholesterolemia have rapidly progressive coronary atherosclerosis with angina pectoris, myocardial infarction, or sudden death at a young age. Selective apheresis on dextran sulfate cellulose columns reduces mortality and may induce regression of coronary lesions. These patients have both increased levels and prolonged circulation residence time of low-density lipoprotein (LDL), which is not removed by cellular receptor. LDL oxidation may play a pivotal role in atherogenesis. LDL undergoes oxidation before being taken up by macrophages and then transformed into arterial wall foam cells. The aim of this study was to investigate LDL oxidation in eight homozygous patients with familial hypercholesterolemia during repeated LDL apheresis. LDL lipid peroxidation, estimated by conjugated-diene absorbance at 234 nm, lipid peroxides, and malondialdehyde showed an increased resistance against oxidation after repeated LDL apheresis. This phenomenon was also observed in the oxidative indexes of protein moiety of LDL (apolipoprotein-B100 fragmentation, trinitrobenzenesulfonic acid reactivity, and electrophoresis agarose mobility). Similarly, cholesteryl esterification was decreased after LDL apheresis. Thus selective LDL apheresis not only decreases the pool of LDL, but it also induces changes that render LDL less susceptible to oxidation. This phenomenon might contribute to reduce coronary atherosclerosis and thus mortality of these particular patients.
 ...
PMID:Decreased low-density lipoprotein oxidation after repeated selective apheresis in homozygous familial hypercholesterolemia. 914 82

Familial hypercholesterolemia is a disorder of lipoprotein metabolism characterized by elevated cholesterol, low-density lipoprotein cholesterol, xanthomas and early onset atherosclerosis. Tendinitis and arthritis have been reported in patients with familial hypercholesterolemia. A report is presented of a 9-year-old girl with an acute arthritic attack who was diagnosed as homozygote familial hypercholesterolemia with hypercholesterolemic arthritis.
 ...
PMID:Arthritis in a patient with homozygous familial hypercholesterolemia. 924 2

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of serum low density lipoprotein (LDL) cholesterol and premature coronary atherosclerosis. In order to elucidate the influence of abnormal glucose metabolism on the development of coronary artery disease (CAD) in FH patients, we examined the prevalence of CAD and characteristics of lipoprotein abnormalities in patients with heterozygous FH who were accompanied by diabetes mellitus (DM) or impaired glucose tolerance (IGT). The subjects of the present study were 150 patients with heterozygous FH, all over 40 years of age. Oral glucose tolerance tests demonstrated that 15 patients had DM and 27 had IGT. The combination of DM or IGT with FH was associated with a further increase in the prevalence of CAD (DM:IGT:normal glucose tolerance (N), 87:59:43%). Furthermore, the prevalence of the stenoses in the distal coronary arteries was significantly higher in the DM group than in the N group, while there was no significant difference in the prevalence of proximal and middle lesions. Serum triglyceride levels were significantly higher in the DM and IGT groups than in the N group (P < 0.01, DM versus N group; P < 0.01, IGT versus N group), while total cholesterol levels were not significantly different. When lipoproteins were analyzed by polyacrylamide gel electrophoresis, the frequency of midband appearance, which implies an increase in remnant lipoproteins, was significantly higher in the DM and IGT groups than in the N group (DM:IGT:N, 87:72:29%, P < 0.01, DM versus N group; P < 0.01, IGT versus N group). Ultracentrifugation analysis of lipoproteins revealed that intermediate density lipoprotein cholesterol was increased in DM and IGT groups compared with the N group. These data suggest that abnormal glucose metabolism may accelerate the development of CAD in FH patients due to an increase in atherogenic remnant lipoproteins in addition to high concentration of LDL. Special attention should be paid in the treatment of FH patients with impaired glucose metabolism, to avoid the advancement of coronary atherosclerosis.
Atherosclerosis 1997 Jul 11
PMID:Characteristics of coronary artery disease and lipoprotein abnormalities in patients with heterozygous familial hypercholesterolemia associated with diabetes mellitus or impaired glucose tolerance. 924 58

Familial hypercholesterolemia is a common autosomal dominant condition characterised by increased low density lipoprotein cholesterol, tendon xanthomas and premature atherosclerosis. Ultrasonography is the diagnostic tool of choice for the detection of tendon xanthomas in the Achilles tendon, demonstrated by the presence of hypoechoeic nodules or an increase in the antero-posterior diameter. It can also be used in screening and clinical follow-up of patients with familial hypercholesterolemia.
 ...
PMID:Tendon xanthoma in familial hypercholesterolemia--a clinical and ultrasonographic study. 926 55

Familial hypercholesterolemia (FH) is characterized by an increased level of LDL cholesterol, tendon xanthomas and an elevated risk of premature coronary artery disease (CAD). FH is caused by different mutations in the low density lipoprotein receptor (LDLR) gene or by a G to A mutation in exon 26 of the apolipoprotein B gene causing familial defective apolipoprotein B-100 (FDB). To compare the phenotypic expression of either defect, we studied 83 patients (76 heterozygous and 7 homozygous persons) with LDLR defects and 33 heterozygous FDB patients from Germany. We took into account other risk factors for CAD. In contrast to earlier studies, our patients where prospectively ascertained from the lipid clinic and tested for the G-A mutation. The average total cholesterol level in plasma was 413.7 mg/dl in LDLR patients and 321.8 mg/dl in FDB patients. Patients with LDLR defects had a significantly higher risk of myocardial infarction, coronary artery bypass graft, positive coronary angiography, atherosclerotic plaques in the carotid arteries and CAD (p<0.01) than patients with FDB. CAD was present in 33% and plaques in the carotid arteries in 82% of the patients with LDLR defects. No patient with FDB had severe CAD, while only 52% had plaques in the carotid arteries (p<0.05). Thus in our study, hypercholesterolemia and premature atherosclerosis were more common in LDLR patients than in FDB patients. We believe that the striking difference in CHD incidence is not sufficiently explained by the higher LDL levels in LDLR patients. A possible explanation may be that in LDLR patients, the metabolism of low density lipoproteins, intermediate density lipoproteins and very low density lipoproteins is disrupted, whereas in FDB patients there is only disruption in apo B-containing LDL.
 ...
PMID:Familial hypercholesterolemia and familial defective apolipoprotein B-100: comparison of the phenotypic expression In 116 cases. 936 Sep 38

Familial hypercholesterolemia (FH) is an autosomal-dominant inherited disorder characterized by high serum low-density lipoprotein (LDL)-cholesterol concentrations, xanthoma formation, and premature atherosclerosis. Homozygous individuals die of vascular disease as children or young adults; heterozygous persons are at high risk for premature cardiovascular death. Mutations in the LDL-receptor gene are responsible for FH. We studied 49 members of a consanguineous Syrian kindred containing 6 homozygous individuals from the same pedigree. Half of the homozygotes had giant xanthomas, while half did not, even though their LDL-cholesterol concentrations were elevated to similar degrees (> 14 mmol/l). Heterozygous FH individuals from this family were also clearly distinguishable with respect to xanthoma size. We performed DNA analysis and were successful in identifying a hitherto not described mutation in this family's LDL receptor. DNA sequence analysis of the LDL-receptor gene revealed a T to C substitution at nucleotide 1,999 in codon 646 of exon 14. We next conducted a segregation analysis, which suggests that a susceptibility gene may explain the formation of giant xanthomas in this family. We raise the hypothesis that the appearance of giant xanthomas in this FH family is controlled by a second gene acting in an autosomal-dominant or recessive fashion. Elucidation of this 'xanthoma' gene may shed additional light on LDL-cholesterol deposition.
 ...
PMID:A xanthomatosis-susceptibility gene may exist in a Syrian family with familial hypercholesterolemia. 941 89

Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in the low density lipoprotein (LDL) receptor gene. Currently, diagnosis of heterozygous FH relies on clinical phenotype; however, the use of clinical criteria for the diagnosis of heterozygous FH does not always permit unequivocable diagnosis of the disease. Molecular diagnosis of FH is clinically valuable especially in regions where founder mutations exist or where polygenic hypercholesterolemia is prevalent. In this paper we report the identification of a novel mutation, a cytosine to guanine substitution, at codon 152 in exon 4 of the LDL receptor gene in a Nova Scotian family clinically diagnosed with heterozygous FH. The mutation creates a recognition sequence for the restriction endonuclease BsrI, and can be readily detected by BsrI restriction analysis of a 160 bp amplicon spanning the mutation. This analysis was used to show that the mutation segregated with the disease in this family and is the probable cause of FH in this kindred.
Atherosclerosis 1998 Jan
PMID:A novel mutation in Exon 4 of the low density lipoprotein receptor gene resulting in heterozygous familial hypercholesterolemia associated with decreased ligand binding. 954 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>