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)

In this cross-sectional study, we examined the associations between lipid profiles and menopausal status, age, and obesity in Taiwanese women. The study population, established in 1990-91, consisted of 671 premenopausal and 872 postmenopausal women from the Chin-Shan Community Cardiovascular Cohort (CCCC). The associations of age, body mass index (BMI), and menopausal status with serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apoproteins (Apo) A-1 and B, and lipoprotein (a) [Lp (a)] were evaluated. The results showed that menopause was associated with significant increases in TC, LDL-C, TG, and Apo B levels (all P < 0.001). Total cholesterol, LDL-C, TG, and Apo B levels increased consistently with BMI in middle-aged women, regardless of menopausal status. Among women aged 45-49, menopausal women had significantly higher levels of TC and LDL-C than premenopausal women (P < 0.01). However, TG and Apo B levels were higher in postmenopausal than in premenopausal women aged 50-54 years (P < 0.05). Standardized regression analyses showed all lipid variables, except those of Apo A1 and Lp (a) before menopause and TC, LDL-C, and Lp (a) after menopause, were significantly associated with BMI (all P < 0.01). We conclude serum lipid levels in Taiwanese women are no more strongly associated with menopause and BMI than with age.
Atherosclerosis 2000 Dec
PMID:Effects of menopause and obesity on lipid profiles in middle-aged Taiwanese women: the Chin-Shan Community Cardiovascular Cohort Study. 1116 31

Previous studies have shown that the amyloid localized to the aortic intima may be a biochemical entity different from other forms of localized amyloid. The amyloid fibril protein in one patient studied consisted of an N-terminal fragment of apolipoprotein A-1 (apo A-1). Since this patient was later shown to carry a missense mutation in the apo A-1 gene, leading to a deletion at position 107 of the mature protein, the question remained whether wild-type apo A-1 is amyloidogenic. In autopsy specimens from the thoracic aorta from 69 individuals, intimal atherosclerotic plaque-related amyloid was present in 11 cases (16%) and amyloid outside plaques in 37 cases (54%). The immunoreactivity of amyloid localized to the aortic intima was evaluated with the aid of antisera against N-terminal segments of apo A-1. The amyloid in association with atherosclerotic plaques was positively labelled by immunohistochemistry. The amyloid fibril protein from one patient, previously shown not to carry any mutation in the apo A-1 gene, was purified and shown by amino acid sequence analysis to be of apo A-1 nature. The result shows that wild-type apo A-1 is amyloidogenic and gives rise to a common localized form of amyloid associated with atherosclerosis.
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PMID:Apolipoprotein A-1-derived amyloid in atherosclerotic plaques of the human aorta. 1118 Jan 76

Human lecithin:cholesterol acyltransferase (LCAT) plays a key role in the biogenesis of circulating high-density lipoprotein-cholesterol (HDL-C) and reverse cholesterol efflux. We investigated the molecular defect in the LCAT gene in a family with low levels of HDL-C. The proband, a 53-year-old woman from Oklahoma City, had a HDL-C level of 0.21 mmol/l. The LCAT activity in the proband was 5 nmol/ml/h and cholesterol esterification rate was 54.2 nmol/ml/h, consistent with LCAT deficiency. Analysis of polymerase chain reaction (PCR) amplified subgenomic fragments of LCAT DNA on polyacrylamide gels revealed heteroduplex bands in the proband and three other affected individuals in exon 6. DNA sequence analyses of the proband's LCAT gene identified a 2 base pair deletion (TC) (base pairs 4544-4545, corresponding to amino acid 255) in the heteroduplex allele, thereby converting Pro(260) to a premature stop codon and a predicted truncated protein of 260 amino acids. This is approximately 60% of the length of the normal translated protein. The heterozygous individuals also revealed significant reduction in apolipoprotein A-1 levels compared with the unaffected family members (n=4). The marked reduction in HDL-C in the proband and sibling suggests a dominant effect of this mutation on HDL-C levels. Furthermore, because the deletion results in a heterozygous allele that can be detected by a simple PCR reaction and polyacrylamide gel-size fractionation, it may be possible to rapidly screen susceptible individuals for the presence of this mutation.
Atherosclerosis 2001 May
PMID:A novel TC deletion resulting in Pro(260)-->Stop in the human LCAT gene is associated with a dominant effect on HDL-cholesterol. 1136 5

Thalassemic (TM) patients are subjected to peroxidative tissue injury because of continuous blood transfusions. It has been documented that circulating LDL from TM patients show marked oxidative modification, that could represent an event leading to atherogenesis. We investigated in 75 beta-TM patients the levels of oxidized LDL antibody (OLAB) to asses their correlation with total cholesterol, LDL and HDL cholesterol, triglycerides Apo A-1 and Apo B. OLAB/mg chol-LDL is greater in TM patients than healthy controls (p<0.001). No correlation was found between OLAB and age, sex of patients, mean blood consumption, mean serum ferritin, mean transaminases, PT, PTT, and fibrinogen. A significant positive correlation was found between OLAB and triglycerides in TM patients (p<0.001). Also a significant correlation was found between OLAB/mg chol-LDL and level of triglycerides in TM patients, but not with total cholesterol, LDL and HDL chols, Apo A-1 and Apo B. On the contrary in the healthy controls this correlation between OLAB and OLAB/mg chol-LDL versus triglycerides was negative and not significant. High levels of OLAB/mg chol-LDL in patients with beta-thalassemia, in absence of evident signs of atherosclerosis, suggest some regulatory mechanisms on the lipid peroxidation which modulate the deposition of ox-LDL in the macrophages and support the hypothesis that both serum iron and triglycerides are involved in the pathogenesis of LDL oxidation.
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PMID:Oxidized LDL antibodies (OLAB) in patients with beta-thalassemia major. 1222 55

Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterised by the production of autoreactive T cells and autoantibodies that may affect every organ system. It has long been established that there is a close association between cholesterol- rich lipoproteins (such as low-density lipoprotein-cholesterol) and cardiovascular disease in patients with SLE. In this study, we evaluated total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLD-cholesterol, apolipoprotein A-1, apolipoprotein B, and cholesterol-rich serum lipoprotein(a) [Lp(a)], which is accepted to be an independent risk factor for cardiovascular disease and for atherosclerosis, in 24 patients (mean age +/- SD 31.4 +/- 9.7 years, range 16-47, 22 F) with active SLE. Twenty-six healthy age- and sex-matched (mean age +/- SD 29.7 +/- 11.3 years, range 18-49 years, 22 F) subjects were included as a control group. In patients with SLE Lp(a) levels, total cholesterol, triglycerides and VLDL-cholesterol were found to be higher and HDL-cholesterol, apolipoprotein A-1 to be lower than those of controls. In conclusion, because serum Lp(a) levels are significantly higher (P<0.01) in patients with SLE, these patients have a risk of developing cardiovascular disease and atherosclerosis. Patients with SLE should be followed up with this in mind.
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PMID:Serum lipoprotein(a) level and its clinical significance in patients with systemic lupus erythematosus. 1244 39

It is widely believed that HDL protects against atherosclerosis by removing excess cholesterol from arterial cells. Lipid-poor HDL apolipoproteins promote efflux of cholesterol, phospholipids, and other lipophilic molecules from cells by an active process mediated by a cell-membrane transporter called the ATP binding cassette transporter A-1 (ABCA1). ABCA1 either directly or indirectly translocates phospholipids and cholesterol to the cell surface, where they appear to form lipid domains that interact with amphipathic alpha-helixes in apolipoproteins. This interaction solubilizes these lipids and generates nascent HDL particles that dissociate from the cell. Binding of apolipoproteins to ABCA1 may also enhance the activity of this lipid-transport pathway. Thus, the apolipoprotein/ABCA1 pathway efficiently clears cells of excess cholesterol that would otherwise accumulate as intracellular lipid droplets. ABCA1 expression is highly induced by cholesterol loading of cells and is also modulated by sterol-independent mechanisms at both the transcriptional and posttranslational level. Studies of human disease and animal models have shown that both an increased availability of apolipoproteins and an enhanced macrophage ABCA1 activity are atheroprotective. These findings implicate the apolipoprotein/ABCA1 pathway as an important therapeutic target for treating cardiovascular disease.
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PMID:HDL apolipoproteins and ABCA1: partners in the removal of excess cellular cholesterol. 1261 80

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Treatment of the disease has contributed dramatically in the long-term survival of the patients and now SLE has become a chronic inflammatory disorder. Present data suggest 5, 10 and 20-year survival rates of 93%, 85% and 68% respectively. Accelerated atherosclerosis and early coronary artery disease have become important causes of death and hospitalisation in SLE patients. Many cardiovascular risk factors can be considered: disease activity (particularly kidney involvement), sedentary life (in nearly 70% of the patients), hyperlipidemia, antiphospholipid antibodies, serum homocysteine and many others. Although traditional risk factors are operative in patients with SLE, the risk for myocardial infarction was increased 8.3 folds after controlling these factors in a study, suggesting that SLE itself was the strongest risk factor for cardiovascular disease. Lipid abnormalities may play a major role in increasing cardiovascular risk in SLE patients who are characterized by elevated triglycerides, very low-density lipoprotein cholesterol (VLDL-C), reduced levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A-1. Anticardioli-pin antibodies may influence lipid levels in SLE; in particular SLE patients with IgG anticardiolipin antibodies had significantly lower HDL-C compared with patients with no anticardiolipin antibodies. Elevation of serum homocysteine is observed in 15% of SLE patients and is significantly associated with the development of stroke and arterial thrombotic events. The antiphospholipid syndrome (APS) is an acquired thrombotic disorder characterised by recurrent venous or arterial thrombosis or recurrent miscarriages, or both, associated with the presence in the serum of IgG or IgM anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC). APS may occur as a primary disorder (PAPS) or associated with connective tissue diseases, mainly systemic lupus erythematosus (secondary APS). Primary and secondary APS are both associated with a significant increase of cardiovascular risk.
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PMID:[Cardiovascular risk factors in systemic lupus erythematosus and in antiphospholipid syndrome]. 1285 54

There are no satisfactory data on circulating concentrations of inflammatory cytokines and their potential relationship with traditional and nontraditional atherosclerosis risk factors in a large healthy young population. The present study was conducted to examine, in 179 healthy families selected from the STANISLAS cohort, the association between interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), orosomucoid, haptoglobin, cell-adhesion molecules (ICAM-1, E-, L- and P-selectin) and lipid parameter concentrations. Age, BMI, white blood cells and tobacco consumption contributed to the variation of IL-6 concentrations. Age and tobacco contributed also to TNF-alpha variation. Taking into account potential covariates, we showed strong positive correlation between IL-6 and both inflammatory markers TNF-alpha and CRP in parents and in offspring (P<0.001). In parents, IL-6 was associated with ICAM-1 and L-selectin (P<0.01), while IL-6 and TNF-alpha predicted E-selectin in offspring only (0.001<P<0.01). Furthermore, IL-6 showed a strong negative relationship with apo A-1 and HDL-cholesterol in females only (P<0.001). This study demonstrated that in a large healthy family population, children included, levels of IL-6 are closely associated with traditional and non-traditional atherosclerosis risk factors. All these data are useful for defining the precise role of cytokines in atherosclerosis mechanisms in physiological conditions.
Atherosclerosis 2003 Oct
PMID:IL-6, TNF-alpha and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort. 1461 8

Biologic therapies involve the utilization of proteins, DNA, antibodies, or other substances derived or synthesized from living tissue for therapeutic effects. There are several biologic therapies in clinical development for the prevention and treatment of atherosclerosis. The most advanced in human trials are apolipoprotein mimetics, which include apolipoprotein A-1 Milano and phospholipid complexes. Infusions of these apolipoprotein mimetics have been demonstrated to reduce atherosclerotic development in both animal models and humans. Autoimmunization to create neutralizing antibodies to cholesteryl ester transfer protein is also in human trials. Gene therapies to reduce low-density lipoproteins and increase high-density lipoproteins are on the horizon, but the ability to safely prolong gene expression in humans will require the development of novel vectors.
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PMID:Biologic therapies for dyslipidemia. 1466 10

Hepatic lipase (HL) plays a role in the metabolism of chylomicron and very low-density lipoprotein remnants, low-density lipoproteins (LDL), and high-density lipoproteins (HDL), which are all implicated in atherosclerosis. Considering the effects of HL on these lipoproteins, it appears that HL has pro- as well as antiatherogenic potential. In line with clinical observations, most effects of HL on lipoprotein metabolism during hypertriglyceridemia may be interpreted as promoting atherosclerosis (formation of small, dense LDL, lowering of HDL levels), whereas most effects during hypercholesterolemia seem to be potentially antiatherogenic (stimulation of reverse cholesterol transport, clearing of intermediate-density lipoprotein). The potential modulation of pro- or antiatherogenics effect of HL by other factors, such as LDL receptor, cholesterol ester transfer protein, lipoprotein lipase, and ATP-binding cassette A-1 activity, is discussed.
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PMID:Hepatic lipase: friend or foe and under what circumstances? 1529 99


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