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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is evidence that indicates the involvement of environmental and genetic factors in the pathogenesis of post-stroke dementia (PSD). In the present work, we examined different polygenic influences on the risk of PSD in a series of stroke patients. We studied 150 consecutive patients evaluated 3 months after suffering acute strokes. All patients were evaluated with a prospective standard protocol and genotyped for vascular disease-associated polymorphisms in the genes coding for apolipoprotein E (including apoE coding and apoE promoter polymorphisms), angiotensin-converting enzyme (ACE) and alpha-1-antichymotrypsin (ACT). Thirty-two cases (21.3%) resulted in dementia 3 months after the stroke. In patients with PSD, the frequency of apoE epsilon 4 (0.08), ACE-D (0.64), ACT-A (0.62) alleles and apoE gene promoter polymorphisms (-491/A, 0.88; -427/C, 0.02) was similar to that of patients without PSD (apoE epsilon 4: 0.10, p=0.79; ACE-D: 0.56, p=0.36; ACT-A: 0.51, p=0.21; -491/A: 0.86, p=1.00; -427/C: 0.08, p=0.29). Our data indicate that PSD is not associated with the genetic risk factors of vascular dementia (VD) that were studied, and that additional factors may contribute to the pathogenesis of PSD.
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PMID:Apolipoprotein E, angiotensin-converting enzyme and alpha-1-antichymotrypsin genotypes are not associated with post-stroke dementia. 1273 93

Hyperlipidemia promotes the chronic inflammatory disease atherosclerosis through poorly understood mechanisms. Atherogenic lipoproteins activate platelets, but it is unknown whether platelets contribute to early inflammatory atherosclerotic lesions. To address the role of platelet aggregation in diet-induced vascular disease, we studied beta3 integrin-deficient mice (lacking platelet integrin alphaIIbbeta3 and the widely expressed nonplatelet integrin alphavbeta3) in two models of atherosclerosis, apolipoprotein E (apoE)-null and low-density lipoprotein receptor (LDLR)-null mice. Unexpectedly, a high-fat, Western-type (but not a low-fat) diet caused death in two-thirds of the beta3-/-apoE-/- and half of the beta3-/-LDLR-/- mice due to noninfectious pneumonitis. In animals from both models surviving high-fat feeding, pneumonitis was absent, but aortic atherosclerosis was 2- to 6-fold greater in beta3-/- compared with beta+/+ littermates. Expression of CD36, CD40L, and CD40 was increased in lungs of beta3-/-LDLR-/- mice. Each was also increased in smooth muscle cells cultured from beta3-deficient mice and suppressed by retroviral reconstitution of beta3. These data show that the platelet defect caused by alphaIIbbeta3 deficiency does not impair atherosclerotic lesion initiation. They also suggest that alphavbeta3 has a suppressive effect on inflammation, the loss of which induces atherogenic mediators that are amplified by diet-induced hyperlipidemia.
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PMID:Beta3 integrin deficiency promotes atherosclerosis and pulmonary inflammation in high-fat-fed, hyperlipidemic mice. 1274 2

The relative amounts of amyloid beta-protein (A beta) in cerebral blood vessels and parenchyma vary considerably amongst patients with Alzheimer's disease (AD). Although several mechanisms have been proposed to explain this variability, the underlying genetic and environmental determinants are still unclear, as are the functional consequences. Polymorphisms in APOE, the gene for apolipoprotein E (ApoE), influence the risk of developing AD and of deposition of A beta within the brain. We examined the relationship between the APOE genotype and the relative extent of accumulation of A beta as plaques within the cerebral parenchyma and in cortical blood vessels in the form of cerebral amyloid angiopathy (CAA), in autopsy brain tissue from 125 AD cases and from 53 elderly, neurologically normal controls of which 19 had CAA without other neuropathological features of AD. In the AD cases, we also assessed whether the severity of CAA was related to the age of onset and duration of dementia, risk factors for atherosclerotic vascular disease, and histologically demonstrable cerebral infarcts or foci of haemorrhage. The APOE genotype was determined by a standard polymerase chain reaction-based method. Paraffin sections of frontal, temporal and parietal lobes were immunolabelled for A beta and the parenchymal A beta load (total A beta minus vessel-associated A beta) was quantified by computer-assisted image analysis. CAA severity was scored for cortical and leptomeningeal vessels. The relevant clinical data were obtained from the database of the South West Brain Bank. In AD, we found the severity of CAA to be strongly associated with the number of epsilon 4 alleles (P < 0.0001) but the parenchymal A beta load to be independent of APOE genotype. Cases with severe CAA had a lower parenchymal A beta load than had those with moderate CAA (P = 0.003). Neither the severity of CAA nor the parenchymal A beta load correlated with age of onset, duration of disease or age at death, and the severity of CAA also did not correlate with the presence of cerebral infarcts or foci of haemorrhage. These findings indicate that possession of the APOE epsilon 4 allele favours vascular over parenchymal accumulation of A beta in AD. This may influence the pathogenesis of neurodegeneration in epsilon 4-associated AD.
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PMID:APOE epsilon 4 influences the pathological phenotype of Alzheimer's disease by favouring cerebrovascular over parenchymal accumulation of A beta protein. 1278 20

Epidemiological studies from the last decade have begun to produce evidence that the perceived joint occurrence of vascular disease and Alzheimer's disease (AD), both common elderly disorders more often believed to occur by chance due to their high prevalence, may now actually have a more pathological significance. The following review discusses some of this evidence and the implications for cognitive decline and the development of AD and how a well-known cardiovascular risk factor gene, the apolipoprotein E (APOE) gene, plays a significant role in the molecular genetics of AD. It also introduces and discusses recent and compelling evidence for the involvement of another well-known cardiovascular risk factor gene, the angiotensin-converting enzyme (ACE1) gene, in the pathogenesis of AD. This role is suggested in terms of recent molecular genetic association evidence implicating the ACE1 insertion/deletion (indel) polymorphism, a more recent large haplotype study that greatly extends the ACE1 indel evidence and incorporates knowledge accrued from previous cardiovascular disease-focused ACE1 haplotype studies. Finally, this paper discusses very recent biological evidence that further supports a role for ACE1 and hypothesises a number of readily testable mechanisms by which the ACE1 enzyme and other components of the renin-angiotensin-aldosterone system may be implicated in increased risk and/or the progression of AD.
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PMID:The renin-angiotensin-aldosterone system and Alzheimer s disease? 1280 89

Although mice deficient in various genes are providing greater insight into the mechanisms of restenosis after angioplasty, there have been limitations with murine models not simulating human vascular disease. To develop a more clinically applicable model of primary atherosclerosis and restenosis following angioplasty of the primary lesion, we fed apolipoprotein E-deficient mice a Western diet and occluded the left common carotid artery for 2 days. Three weeks after flow was restored, the temporarily occluded carotids demonstrated atherosclerotic lesions containing foam cells, cholesterol clefts, necrotic cores, and fibrous capsules. The atherosclerotic carotids in other animals underwent angioplasty with a beaded probe, resulting in plaque and medial layer disruption. Three weeks after angioplasty, although there was significant neointimal lesion formation, the luminal narrowing did not change significantly secondary to overall vessel enlargement (positive remodeling). Neointimal lesions were composed of smooth-muscle cells and extracellular matrix observed adjacent to the original atherosclerotic plaques. Similarly, even at 3 months after the angioplasty the lumen was maintained despite greater neointimal lesion formation caused by progressive positive remodeling. This new murine model of primary atherosclerosis and postangioplasty intimal hyperplasia and remodeling mimics the human disease pattern of postangioplasty intimal hyperplasia. Used in transgenic animals, this model will likely facilitate understanding of the mechanisms of restenosis in humans.
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PMID:A model of primary atherosclerosis and post-angioplasty restenosis in mice. 1287 96

Historically, studies of atherosclerosis and vascular disease have been performed in larger animal species, other than small rodents. Published information on vascular dissection in mice, because of the technical challenges it presents, has been limited. However, with the advent of transgenic technology, such procedures are becoming more commonplace. In particular, mice in which genes such as LDL or apolipoprotein E have been 'knocked-out' have recently provided powerful small animal models for such work. The methodology presented provides a clear, accurate, and detailed description for removing the entire mouse aorta for further analysis in atherogenic investigations. Thus, our article likely will provide a useful guide to those new to this technique, and for researchers undertaking similar studies, and the technique could be adapted to other species easily.
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PMID:Vascular microdissection, perfusion, and excision of the murine arterial tree for use in atherogenic disease investigations. 1451 May 26

Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways. Elevated plasma homocysteine (hyperhomocysteinemia) is associated with occlusive vascular disease. Whether homocysteine per se or a coincident metabolic abnormality causes vascular disease is still an open question. Animals with genetic hyperhomocysteinemia have so far not displayed atheromatous lesions. However, when methionine-rich diets are used to induce hyperhomocysteinemia, vascular pathology is often observed. Such studies have not distinguished the effects of excess dietary methionine from those of hyperhomocysteinemia. We fed apolipoprotein E-deficient mice with experimental diets designed to achieve three conditions: (i) high methionine intake with normal blood homocysteine; (ii) high methionine intake with B vitamin deficiency and hyperhomocysteinemia; and (iii) normal methionine intake with B vitamin deficiency and hyperhomocysteinemia. Mice fed methionine-rich diets had significant atheromatous pathology in the aortic arch even with normal plasma homocysteine levels, whereas mice fed B vitamin-deficient diets developed severe hyperhomocysteinemia without any increase in vascular pathology. Our findings suggest that moderate increases in methionine intake are atherogenic in susceptible mice. Although homocysteine may contribute to the effect of methionine, high plasma homocysteine was not independently atherogenic in this model. Some product of excess methionine metabolism rather than high plasma homocysteine per se may underlie the association of homocysteine with vascular disease.
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PMID:The atherogenic effect of excess methionine intake. 1465 34

In recent years, it is becoming apparent that genes may play an important role in the development of late-onset Alzheimer's disease (LOAD), and genetic studies could unravel new clues. Based on a growing vascular hypothesis for the pathogenesis of LOAD and other dementias, there is increasing interest for environmental and genetic vascular factors. Polymorphisms in different susceptibility genes already implicated in vascular disease risk are now also being suggested as possible genetic markers for increased risk of developing LOAD; however, many of these studies have shown conflicting results. Thus far, the apolipoprotein E (APOE) gene seems to be the only vascular susceptibility factor that is agreed to play a role in the multifactorial pathogenesis of AD although emerging genetic and biological evidence is now strengthening the case for additional inclusion of angiotensin I-converting enzyme 1 (ACE1) into this category. This review will focus on the current knowledge on genetic and nongenetic vascular factors likely to be involved in LOAD, with special emphasis placed on the APOE and ACE1 genes.
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PMID:Vascular risk and genetics of sporadic late-onset Alzheimer's disease. 1471 17

A 74-year-old woman had a history over 25 years of endarterectomy of both renal arteries, iliac venous thrombosis, pulmonary embolism, left internal carotid artery endarterectomy, coronary angioplasty, aortocoronary bypass grafting, occlusion of the right axillary artery, lower-limb claudication due to common iliac artery aneurysm, external iliac artery stenosis, multiple femoral artery stenoses, bifurcational stent grafting, occlusion of the left brachial artery and the right external iliac artery, and stroke. Assessment of the risk-factor profile revealed an absence of classic risk factors but the presence of the factor V Leiden mutation, the methylenetetrahydrofolate reductase AI298C mutation, the HFE C282Y mutation, plasminogen activator inhibitor-1 gene mutation, the -455 G/A fibrinogen gene polymorphism, the epsilon3/epsilon4 apolipoprotein E -675 4G gene polymorphism, and hyperhomocysteinemia. This case shows that severe, generalized, occlusive vascular disease may be due to the combination of various genetic risk factors for atherosclerosis and venous thromboembolism.
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PMID:Risk-factor profile in severe, generalized, obliterating vascular disease. 1474 32

To explore the clinical effects of inflammation associated with vascular deposits of the amyloid beta peptide (A beta), we analyzed 42 consecutive patients with pathologically diagnosed cerebral amyloid angiopathy (CAA) for evidence of an inflammatory response. Inflammation with giant-cell reaction surrounding amyloid-laden vessels was identified in 7 of the 42 cases. The clinical symptoms in each of the seven were subacute cognitive decline or seizure rather than hemorrhagic stroke, the primary clinical presentation in 33 of 35 patients with noninflammatory CAA (p < 0.001). Inflammatory CAA also was associated with radiographic white matter abnormalities, significantly younger age at presentation, and a marked overrepresentation of the apolipoprotein E epsilon 4/epsilon 4 genotype (71% vs 4%, p < 0.001). Of the six inflammatory CAA patients with available follow-up information, five demonstrated clinical and radiographic improvement after immunosuppressive treatment. The syndrome of CAA-related perivascular inflammation appears to represent a subset of CAA with clinically distinct symptoms that may respond to immunosuppressive treatment. These data add to evidence that inflammation against A beta can cause vascular dysfunction, a potential mechanism for the toxic response recently observed in clinical trials of A beta immunization.
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PMID:Clinical manifestations of cerebral amyloid angiopathy-related inflammation. 1475 29


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