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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is more common among African Americans than Americans of European descent. However, the genetic etiology has not been defined. Similarly, lipoprotein (Lp) (a), an independent risk factor for cardiovascular disease, is higher among African Americans. To explore the relationship between Lp (a) and hypertension, we measured the blood pressure of transgenic mice expressing apolipoprotein(a), the unique protein moiety of lipoprotein(a). As controls, we also determined blood pressure for apoE deficient mice, low density lipoprotein-receptor (LDL-R) deficient mice, and wild type C57Bl/6 mice. Apo(a) expression was not associated with hypertension. Surprisingly, LDL-R deficient mice exhibited male-associated hypertension. This observation could explain the higher incidence of atherosclerosis in male LDL-R deficient mice and human familial hypercholesterolemia (FH) patients. LDL-R deficient mice were more sensitive to photochemically induced cerebral stroke. However, this hypersensitivity was only modestly associated with sexual dimorphism. The presented data suggest that LDL-R deficiency results in hitherto unrecognized changes in the vascular tone.
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PMID:Male-associated hypertension in LDL-R deficient mice. 964 16

The human plasma lipoprotein Lp(a) has gained considerable clinical interest as a genetically determined risk factor for atherosclerotic vascular diseases. Numerous (including prospective) studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke and peripheral atherosclerosis. Lp(a) consists of a large LDL-like particle to which the specific glycoprotein apo(a) is covalently linked. The apo(a) gene is located on chromosome 6 and belongs to a gene family including the highly homologous plasminogen. Lp(a) plasma concentrations are controlled to a large extent by the extremely polymorphic apo(a) gene. More than 30 alleles at this locus determine a size polymorphism. The size of the apo(a) isoform is inversely correlated with Lp(a) plasma concentrations, which are non-normally distributed in most populations. To a minor extent, apo(a) gene-independent effects also influence Lp(a) concentrations. These include diet, hormonal status and diseases like renal disease and familial hypercholesterolemia. The standardisation of Lp(a) quantification is still an unresolved problem due to the enormous particle heterogeneity of Lp(a) and homologies of other members of the gene family. Stability problems of Lp(a) as well as statistical pitfalls in studies with small group sizes have created conflicting results. The apo(a)/Lp(a) secretion from hepatocytes is regulated at various levels including postranslationally by apo(a) isoform-dependent prolonged retention in the endoplasmic reticulum. This mechanism can partly explain the inverse correlation between apo(a) size and plasma concentrations. According to numerous investigations, Lp(a) is assembled extracellularly from separately secreted apo(a) and LDL. The sites and mechanisms of Lp(a) removal from plasma are only poorly understood. The human kidney seems to represent a major catabolic organ for Lp(a) uptake. The underlying mechanism is rather unclear; several candidate receptors from the LDL-receptor gene family do not or poorly bind Lp(a) in vitro. Lp(a) plasma levels are elevated over controls in patients with renal diseases like nephrotic syndrome and end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus mainly result from insufficient sample sizes in numerous studies. Large studies and those including apo(a) phenotype analysis have come to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In non-insulin-dependent diabetics Lp(a) is not elevated. Several rare disorders, such as LCAT and LPL deficiency, as well as liver diseases and abetalipoproteinemia are associated with low plasma levels or lack of Lp(a).
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PMID:Genetics and metabolism of lipoprotein(a) and their clinical implications (Part 1). 1006 65

We selected 247 subjects from 29 large familial hypercholesterolemia (FH) kindreds from 550 probable FH subjects in Emilia Romagna (Italy) on the basis of LDL-cholesterol plasmatic levels and family trees, in order to define the best diagnostic criteria for heterozygous patients. Familial hypercholesterolemia is a monogenic disease of cholesterol metabolism inherited as an autosomal dominant trait and characterised by early cardiovascular disease. A low xanthomas and xanthelasmas prevalence was found (8.6%); coronary heart disease (CHD) death occurs very frequently in heterozygous males (72% of all deaths; mean age at death 52 years), while in females the primary cause of death was thrombotic stroke (55%; mean age 69 years). Total cholesterol (TC) mean values were 389.8 (m) and 373.3 mg/dl (f) for FH trait carriers, and 223.3 (m) and 228.8 (f) for healthy relatives. No age-related change in TC was found in heterozygotes, while unaffected relatives of FH families showed mean TC and LDL-C values, and a TC frequency distribution and a TC age-related increasing trend similar to the expected values for the Italian population. The TC frequency distribution curve appeared bimodal, with a mid-point between heterozygous and homozygous FH modal values of 280 mg/dl. To identify the FH patients, the final FH heterozygosity risk was evaluated in an unselected free-living population (from 0.07 to 0.8%, respectively, for TC between 265-274 and 295-304 mg/dl) and in hypercholesterolemic families (31 to 83%, and the same TC classes). Our conclusion is that the clinical picture is rarely pathognomonic, while the FH heterozygosity final risk evaluation and the 280 mg/dl cut-off point can be used to guide the practical clinical diagnosis and to select the patients destined for B-E receptor activity evaluation.
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PMID:A suggestion for familial hypercholesterolemia (FH) heterozygosity clinical diagnosis based on epidemiological observations in a large Italian population. 1085 74

Atherosclerosis is the commonest lesion of blood vessels and is responsible for life-threatening events such as myocardial infarction and stroke. In the last two decades a series of excellent studies unraveled biochemical mechanisms that provided the background for a theory of atherogenesis. This theory is centered on foam cells and on free radical-mediated modification of low density lipoprotein (LDL). Foam cells are the main cell type of atherosclerotic lesions and originate from monocytes migrated from blood and from smooth muscle cells of the arterial wall. Foam cells are engulfed of lipids taken from LDL. Paradoxically, accumulation of LDL in developing foam cells does not occur via the classic LDL receptor. Incubation of macrophages with even very high concentrations of LDL does not appreciably increase cholesterol content. Chemically modified LDL easily enter the cells of atherosclerotic plaque via an unregulated receptor, the scavenger receptor. The most studied chemical modification of LDL is that induced by free radicals.
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PMID:The oxidant stress hypothesis of atherogenesis. 1183 91

We have used a rat model of focal cerebral ischemia to investigate changes in gene expression that occur during stroke. To monitor these changes, we employed representational difference analysis-polymerase chain reaction (PCR). A total of 128 unique gene fragments were isolated, and we selected 13 of these for quantitative reverse transcriptase-PCR analysis. Of these 13 genes, we found seven that were differentially expressed. Four of these genes have not previously been implicated in stroke, and include neuronal activity regulated pentraxin (Narp), cysteine rich protein 61 (Cyr61), Bcl-2 binding protein BIS (Bcl-2-interacting death suppressor), and lectin-like ox-LDL receptor (LOX-1). We demonstrated differential expression of each gene by quantitative PCR analysis, and in the case of LOX-1, we further confirmed differential expression by in situ hybridization. LOX-1 expression is induced greater than ten fold at the core lesion site, and is essentially localized to the ipsilateral half of the brain. LOX-1 appears to be expressed in a non-neuronal cell type, and it does not appear to be expressed in vascular endothelial cells within the brain. This suggests that LOX-1 may serve a novel function in the brain.
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PMID:Identification of differentially expressed genes induced by transient ischemic stroke. 1200 27

Lipoprotein (LP) metabolism plays a pivotal role in atherogenesis. Breakdown of triglyceride (TG) rich lipoproteins, both of exogenous--chylomicrones and endogenous--very low density lipoproteiny (VLDL) produces remnant lipoproteins after repeated action of lipoprotein lipase (LPL). Atherogenity of remnant lipoprotein has been proved. Also atheroprotective high density lipoproteins (HDL) are produced from surface of TG rich lipoproteins during their lipolysis. Protective role of HDL particles in atherogenesis is manifested by reverse cholesterol transport from all extrahepatic cells to the liver including cells of the arterial wall. Plasma concentration of atherogenic low density lipoproteins (LPL) is regulated by the production rate of VLDL in the liver on the one hand and their utilization by selective LDL receptors (mainly in the liver) on the other hand. Number of functioning LDL receptors is regulated genetically (gene for own LDL receptor and gene for both ligands--apoprotein B and apoprotein E) and also by environmental factors. Diet low in saturated fat and cholesterol and rich in dietary fibres increases number of LDL receptors and consequently decreases LDL cholesterol concentration. Monocytes entering arterial wall when intravasal and then subendothelial concentration of LDL is increased absorb LDL and predominantly oxidized LDL by scavenger receptors. During this repeated process they are changed to macrophages, residual macrophages and foam cells. Production of foam cells represents a starting point in atherogenesis but their high presence is typical also for advanced vulnerable atherosclerotic lesions, which are prone to rupture producing clinical complication--myocardial infarction and stroke.
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PMID:[Lipid metabolism in atherogenesis]. 1269 88

The recent focus on emerging cardiovascular risk factors, such as C-reactive protein, homocysteine, and small, dense low-density lipoprotein (LDL), may give the false impression that the current approach to the assessment of cardiovascular disease risk fails to identify a large section of the high-risk population. On the contrary, the new guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) propose classifying an enormous number of individuals, including people with any form of atherosclerotic disease, diabetes, and a combination of major risk factors, into the category of high risk (>20% likelihood of a major coronary event or stroke in 10 years). Considering the widespread prevalence of the metabolic syndrome-a high-risk condition characterized by mild hypertension, mild dyslipidemia, hyperglycemia, and visceral obesity-we may be faced with the challenge of implementing aggressive risk reduction therapies in as much as 30% of the adult US population. From the point of view of risk assessment, a practical approach is to follow the NCEP guidelines (ie, place patients with diabetes and those with atherosclerotic complications in the highest risk category), apply the Framingham calculation to determine risk in people with common risk factors, and initiate early intervention in people who have familial hypercholesterolemia (LDL cholesterol >200 mg/dL) or a family history of early cardiovascular disease. The emerging risk factors may be useful for further stratifying risk in individuals with intermediate risk and the presence of risk factors not included in the Framingham calculation.
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PMID:A practical approach to risk assessment to prevent coronary artery disease and its complications. 1286 51

Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lpa) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lpa levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low-density lipoprotein (LDL) apheresis was performed over 95.6 +/- 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein a (Lpa), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side-effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement in general well-being and increased performance were experienced by 44 of 45 patients. The present data demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia resistant to maximum conservative therapy is very effective and safe even in long-term application.
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PMID:Low-density lipoprotein apheresis: an overview. 1288 19

Ever more unexpected roles for the LDL receptor gene family in a variety of cellular signaling pathways continue to emerge. Three recent studies now add another function to this collection. By interacting with active tissue-type plasminogen activator, LDL receptor-related protein appears to control permeability of the blood-brain barrier, vascular tone, and the expression of MMPs. All of these parameters impact upon postischemic infarct size following stroke. These novel findings are discussed in the context of known mechanisms of signaling by the LDL receptor family.
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PMID:LRP: a bright beacon at the blood-brain barrier. 1461 54

Antiphospholipid syndrome is considered to be a cause of an acquired hypercoagulable state leading to stroke and transient ischemic attack. Antiphospholipid antibodies (aPL) comprise a heterogeneous group of autoantibodies. Among them, lupus anticoagulant (LA) and beta 2-glycoprotein I dependent anticardiolipin antibody (beta 2-GPI aCL) are important and commonly measured. Recently, LA has been considered to be closely related to phosphatidylserine anti-prothrombin antibody. APL is an independent risk factor for first-ever ischemic stroke and a prognostic marker of recurrent stroke. The precipitating factors for the occurrence of stroke are the presence of beta 2-GPI-dependent aCL, a GPL aCL level of more than 40, and the simultaneous presence of lupus anticoagulant. Several mechanisms are believed to be involved in the thrombotic process in patients with antiphospholipid antibodies. Human activated protein C functions as a potent anticoagulant in human plasma by inhibiting the activity of coagulation cofactors Va and VIIIa. Activation of protein C is impaired in patients with aPL. Recently, the presence of aPL has been considered to be contributory factor for the development of atherosclerotic lesions. Transgenic mouse lacking the LDL receptor develop accelerated arteriosclerosis upon immunization with beta 2-GPL Several therapeutic options are available for the prevention of ischemic stroke in patients with aPL, such as antiplatelet, anticoagulant, and immunosuppressive therapy. The rate of recurrence in patients undergoing antiplatelet and anticoagulation combination therapy was found to be lower than that in patients receiving other forms of therapy. The WARSS-APASS collaborative study showed that there was no difference in the recurrence rate between aPL patients receiving antiplatelet or anticoagulation therapy alone. APL has been investigated in other neurological disorders such as multiple sclerosis, chorea, migraine and convulsion. The association of aPL with multiple sclerosis remains debatable. APL could be a contributory factor for the development of convulsion, but not for migraine.
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PMID:[Neurological aspects in antiphospholipid syndrome]. 1515 54


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