Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of eicosapentaenoic acid (EPA) on serum lipoprotein (a) (Lp(a)) and other lipid levels in patients with vascular disease were examined. The serum levels of Lp(a), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) were measured in 24 patients with vascular disease. An elevated serum Lp(a) level (39 +/- 22 mg/dl) was noted in 9 patients, elevated total cholesterol level (263 +/- 31 mg/dl) in 12 patients, elevated triglyceride level (240 +/- 98 mg/dl) in 10 patients and elevated LDL level (651 +/- 88 mg/dl) in 6 patients before administration of EPA. EPA (1,800 mg/day) was given to these patients for long periods ranging from 6 to 24 months. The serum levels of Lp(a), TC, TG and LDL were lowered significantly (p < 0.05) after EPA administration for 12 and 18 months, for 6, 12, 18 and 24 months, for 18 months and for 12 and 18 months, respectively. These findings indicated that long-term administration of EPA may lower Lp(a) and serum lipids, which is beneficial for patients with various arterial diseases in terms of preventing progression of the disease.
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PMID:The long-term effect of eicosapentaenoic acid on serum levels of lipoprotein (a) and lipids in patients with vascular disease. 922 17

Although the mechanism by which lipoprotein(a) [Lp(a)] contributes to vascular disease remains unclear, consequences of its binding to the vessel surface are commonly cited in postulated atherogenic pathways. Because of the presence of plasminogen-like lysine binding sites (LBS) in apo(a), fibrin binding has been proposed to play an important role in Lp(a)'s vascular accumulation. Indeed, LBS are known to facilitate Lp(a) fibrin binding in vitro. To examine the importance of apo(a) LBS in Lp(a) vascular accumulation in vivo, we generated three different apo(a) cDNAs: (a) mini apo(a), based on wild-type human apo(a); (b) mini apo(a) containing a naturally occurring LBS defect associated with a point mutation in kringle 4-10; and (c) human- rhesus monkey chimeric mini apo(a), which contains the same LBS defect in the context of several additional changes. Recombinant adenovirus vectors were constructed with the various apo(a) cDNAs and injected into human apoB transgenic mice. At the viral dosage used in these experiments, all three forms of apo(a) were found exclusively within the lipoprotein fractions, and peak Lp(a) plasma levels were nearly identical (approximately 45 mg/dl). In vitro analysis of Lp(a) isolated from the various groups of mice confirmed that putative LBS defective apo(a) yielded Lp(a) unable to bind lysine-Sepharose. Quantitation of in vivo Lp(a) vascular accumulation in mice treated with the various adenovirus vectors revealed significantly less accumulation of both types of LBS defective Lp(a), relative to wild-type Lp(a). These results indicate a correlation between lysine binding properties of Lp(a) and vascular accumulation, supporting the postulated role of apo(a) LBS in this potentially atherogenic characteristic of Lp(a).
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PMID:Lipoprotein(a) vascular accumulation in mice. In vivo analysis of the role of lysine binding sites using recombinant adenovirus. 929 16

Lipoprotein (a) [Lp(a)] is a LDL-like particle linked to an apo-lipoprotein (a) which has high sequence homology with plasminogen that gives Lp(a) thrombogenic properties in addition to atherogenic capacity. Many epidemiological studies have shown that a high plasma level of Lp(a) is a risk factor for coronary, cerebral and peripheral atherosclerosis. Out of thirteen prospective studies, ten have confirmed this result. The negative results from the three remaining studies were probably due to either inadequate storage of the samples or preventive drug treatment given to the patients during the studies. This review of the literature clearly demonstrates the relationship between Lp(a) and atherosclerosis and the need to measure Lp(a) in order to better evaluate the risk of atherosclerotic vascular disease especially in patients with a hyper LDLemia, an early cardio- or cerebrovascular disease or a family history of atherosclerosis.
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PMID:[Lipoprotein (a), a cardiovascular risk factor: importance of its determination in current clinical practice]. 966 19

Recent evidence indicates a potential role for the plasmin/plasminogen activator system in the prevention of atherosclerotic vascular disease. Fibrin deposition is a common histologic feature of the tissues of mice that are genetically deficient in one or more key components of the fibrinolytic system. Cell surface receptors may support fibrinolytic surveillance in both intravascular and extravascular locations by stimulating the efficiency plasmin generation and by protecting plasmin from its inhibitors. In vitro studies suggest that the endothelial cell receptor, annexin II, which independently binds both plasminogen and t-PA, could play a key role in the process. Binding of plasminogen to annexin II is specifically inhibited in the presence of excess concentrations of the atherogenic LDL-like particle Lp(a). Similarly, t-PA binding to annexin II is blocked by homocysteine, a sulfhydryl-containing amino acid that is associated with atherogenesis and that directly derivatizes the t-PA binding domain of annexin II. Elucidation of the precise role of annexin II in fibrinolytic surveillance, however, will await in vivo study.
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PMID:Modulation of annexin II by homocysteine: implications for atherothrombosis. 980 20

Coronary artery disease is a leading cause of death in France. Some of its risk factors are well identified such as age, smoking, high blood pressure and dyslipidemia, but some others such as lipoprotein (a) (Lp(a)) are still under investigation. Lp(a) is an LDL-like particle to which is linked an apolipoprotein (a). The latter shows a high sequence homology with plasminogen that gives Lp(a) thrombogenic properties in addition to its atherogenic capacity. Many epidemiological studies have shown that a high plasma level of Lp(a) is a risk factor for coronary, cerebral and peripheral atherosclerosis. Out of thirteen prospective studies, ten have confirmed this result. The negative results from the three remaining studies were probably due to either the inadequate storage of the samples or the preventive drug treatment given to the patients during the studies and to the lack of standardization of Lp(a) assays. More over it has been shown that beside high plasma Lp(a) level, the presence of a low molecular weight Apo(a) isoform is also related to a higher incidence of coronary artery disease. This review of the literature clearly demonstrates the relationship between Lp(a) and atherosclerosis, and the need to measure Lp(a) in order to better evaluate the risk of atherosclerotic vascular disease especially in patients with a hyper LDLemia an early cardio- or cerebrovascular disease or a family history of atherosclerosis. Management of patients with high Lp(a) concentrations should be directed at minimizing all other risk factors for atherosclerotic disease.
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PMID:[Lipoprotein(a): risk factor for atherosclerotic vascular disease important to take into account in practice]. 1021 Jul 42

We measured the serum lipid profile, together with plasma fibrinogen and serum lipoprotein(a) (Lp[a]), glucose, bilirubin, and albumin levels in 491 patients (310 men) who were referred for the management of primary dyslipidemia. All these variables have been shown to predict vascular events. The patients were not taking lipid-lowering drugs; hypertension was present in 156 (31.7%) of them. Of the hypertensive patients, 52 (33%) were not receiving any treatment to control their blood pressure. This omission was not due to a lower prevalence of established vascular disease. The treated hypertensives were divided into three groups according to their treatment: 62 were taking lipid-hostile antihypertensives (beta-blockers, thiazides), 37 were taking lipid-neutral antihypertensives (angiotensin converting enzyme inhibitors, Ca-channel blockers, angiotensin II receptor blockers, indapamide sustained release), and five were taking lipid-friendly antihypertensives (doxazosin). Lipid-hostile antihypertensive drugs were associated with a significantly higher fibrinogen concentration when compared with untreated hypertensives or those taking lipid-neutral/lipid-friendly drugs (median values: 383, 353, and 336 mg/dL, respectively; P < .01). Lipid-neutral/lipid-friendly antihypertensive drugs were associated with lower Lp(a) levels when compared with untreated hypertensives (median values: 22 and 45 mg/dL, respectively; P < .05). The serum bilirubin level was significantly lower in the untreated hypertensives when compared with normotensives or the treated hypertensives. There were no significant differences in lipids, glucose, or albumin among the groups of hypertensives or normotensives. The influence of antihypertensive drugs on additional cardiovascular risk factors should be considered when selecting medication to reduce blood pressure.
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PMID:Effect of hypertension and its treatment on lipid, lipoprotein(a), fibrinogen, and bilirubin levels in patients referred for dyslipidemia. 1041 64

Genetic risk factors implicated in stroke are reviewed. There is evidence that family history of vascular disease is an independent risk factor for stroke. Twin studies demonstrated that there is a genetic component for stroke. I review the possible pathogenetic relevance of several vascular risk factors, namely dyslipoproteinemia, Lp(a), ApoE, homocystein, and prothrombotic states. Finally, I carry out an overview of genetic monogenic disorders manifesting with embolic stroke, thrombotic stroke or hemorrhagic stroke. This review corroborates that there are many genetic risk factors of stroke, though further studies will be necessary to establish whether or not these factors are pathogenetically independent from acquired factors.
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PMID:[From the genetics to the prevention of stroke]. 1069 59

It is well recognized that blood lipoprotein A [Lp(a)] levels constitute an important risk factor for atherosclerotic vascular disease. In some populations, mainly Caucasian, Lp(a) levels and coronary heart disease (CHD) risk are determined by the pattern of apolipoprotein a [apo(a)] polymorphism. It is currently unclear if these observations apply to other populations and ethnic groups. The aim of the current study is to determine to what extent known apo(a) polymorphisms associate with development of CHD in a Kuwaiti Arab population. Serum Lp(a) levels were measured by enzyme-linked immunosorbent assay and apo(a) isoforms determined by a high-resolution sodium dodecyl sulphate/agarose gel electrophoresis with immunoblotting in two groups of Kuwaiti subjects: healthy controls (n = 140) and subjects with CHD (n = 140). Blood lipids and anthropometric parameters were also determined in these subjects by standard methods. Serum Lp(a) levels were greater in those with CHD than in those in the healthy group (P < 0.001). There was no consistent trend in the pattern of serum Lp(a) levels found with specific apo(a) isoforms in either group of subjects. There was, therefore, no simple relationship between the isoform pattern (and number of kringle-IV repeats) and serum Lp(a) concentration, unlike in certain other populations. Additionally, almost identical proportions of subjects in either group had single-banded (homozygous, approximately 70%), double-banded (heterozygous, approximately 23%) and no-band (null, approximately 7%) phenotypes. The distribution of the five identified isoforms (F, S1, S2, S3 and S4) also was almost identical for both groups of subjects, whether homozygous or heterozygous, and whether classified into fast-moving (F, S1 and S2) or slow-moving (S3 and S4) isoforms. We conclude that the frequency and pattern of distribution of apo(a) phenotypes did not differ significantly between healthy control Kuwaiti Arab subjects and those with CHD. It is thus unlikely that an individual's apo(a) phenotype can predict both serum Lp(a) level and risk for CHD, irrespective of race and/or ethnic grouping.
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PMID:Apo(a) isoforms do not predict risk for coronary heart disease in a Gulf Arab population. 1081 52

The risk factor, Lipoprotein(a), [(Lp(a)], has been measured in numerous clinical studies by a variety of immunochemical assay methods. It is becoming apparent that for many of these assays antibody specificity towards the apolipoprotein(a) [apo(a)] repetitive component [the kringle 4-type 2 repeats] and apo(a) size heterogeneity can significantly affect the accuracy of serum Lp(a) measurements. To address this issue, we investigated whether our current in house Lp(a) [Mercodia] assay showed such bias compared to a recently available assay [Apo-Tek], claiming to possess superior capability for isoform-independent measurement of Lp(a). Levels of Lipoprotein(a) by both Apo-Tek and Mercodia assays correlated inversely with apo(a) isoform sizes. No significant differences were observed between assays in ranges of Lp(a) concentration within each isoform group. The Mercodia assay exhibited similar isoform-independent behaviour to that of Apo-Tek for the quantitation of serum Lipoprotein(a). Essentially identical results were obtained by the two methods, suggesting that Mercodia assay's capture monoclonal antibody also (as is the case for Apo-Tek) does not recognize the kringle 4-type 2 repetitive domain of apo(a). Correlation of Lp(a) concentrations in patient specimens between Apo-Tek and Mercodia assays showed good agreement, although an overall higher degree of imprecision and non-linearity was noted for the Apo-Tek procedure. A change-over to the Apo-Tek assay would therefore not improve on our current assessment of risk contribution from Lp(a) for atherosclerotic vascular disease in individuals with measurable levels of circulating Lipoprotein(a).
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PMID:Evaluation of a new apolipoprotein(a) isoform-independent assay for serum Lipoprotein(a). 1088 41

The new therapeutic options available to clinicians treating dyslipidaemia in the last decade have enabled effective treatment for many patients. The development of the HMG-CoA reductase inhibitors (statins) have been a major advance in that they possess multiple pharmacological effects (pleiotropic effects) resulting in potent reductions of low density lipoproteins (LDL) and prevention of the atherosclerotic process. More recently, the newer fibric acid derivatives have also reduced LDL to levels comparable to those achieved with statins, have reduced triglycerides, and gemfibrozil has been shown to increase high density lipoprotein (HDL) levels. Nicotinic acid has been made tolerable with sustained-release formulations, and is still considered an excellent choice in elevating HDL cholesterol and is potentially effective in reducing lipoprotein(a) [Lp(a)] levels, an emerging risk factor for coronary heart disease (CHD). Furthermore, recent studies have reported positive lipid-lowering effects from estrogen and/or progestogen in postmenopausal women but there are still conflicting reports on the use of these agents in dyslipidaemia and in females at risk for CHD. In addition to lowering lipid levels, these antihyperlipidaemic agents may have directly or indirectly targeted thrombogenic, fibrinolytic and atherosclerotic processes which may have been unaccounted for in their overall success in clinical trials. Although LDL cholesterol is still the major target for therapy, it is likely that over the next several years other lipid/lipoprotein and nonlipid parameters will become more generally accepted targets for specific therapeutic interventions. Some important emerging lipid/lipoprotein parameters that have been associated with CHD include elevated triglyceride, oxidised LDL cholesterol and Lp(a) levels, and low HDL levels. The nonlipid parameters include elevated homocysteine and fibrinogen, and decreased endothelial-derived nitric oxide production. Among the new investigational agents are inhibitors of squalene synthetase, acylCoA: cholesterol acyltransferase, cholesteryl ester transfer protein, monocyte-macrophages and LDL cholesterol oxidation. Future applications may include thyromimetic therapy, cholesterol vaccination, somatic gene therapy, and recombinant proteins, in particular, apolipoproteins A-I and E. Non-LDL-related targets such as peroxisome proliferator-activating receptors, matrix metalloproteinases and scavenger receptor class B type I may also have clinical significance in the treatment of atherosclerosis in the near future. Before lipid-lowering therapy, dietary and lifestyle modification is and should be the first therapeutic intervention in the management of dyslipidaemia. Although current recommendations from the US and Europe are slightly different, adherence to these recommendations is essential to lower the risk of atherosclerotic vascular disease, more specifically CHD. New guidelines that are expected in the near future will encompass global opinions from the expert scientific community addressing the issue of target LDL goal (aggressive versus moderate lowering) and the application of therapy for newer emerging CHD risk factors.
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PMID:Current, new and future treatments in dyslipidaemia and atherosclerosis. 1092 30


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