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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a major risk factor for clinically significant atherosclerotic vascular disease in Western Society, although the link between these conditions remains very poorly understood. Recent studies which are reviewed here have demonstrated that major arterial intimal and medial abnormalities occur as a result of hypertension. These include functional changes in endothelial permeability as well as alterations in the endothelial cells themselves with an increase in their turnover and number and distinct changes in morphology. However, endothelial cell loss leading to denudation of the arterial intimal surface appears to be relatively uncommon. Intimal and medial thickening are consistent features of hypertension and result from increases in both cellular and extracellular components. The cells accumulating in the subendothelial space appear to be of both blood-borne and medial origins, although their complete characterization has not been performed as yet. The adherence of blood cells to the endothelial surface appears to be promoted by the presence of hypertension along with their increased entry into the intima through endothelial cell junctions. Medial thickening with hypertension is attributable primarily to increased smooth muscle cell mass, although enhanced deposition of collagen and elastin plays a contributory role. Recent data would indicate that smooth muscle cell hypertrophy rather than hyperplasia is primarily responsible for the greater smooth muscle mass with hypertension. Although elevated DNA content of hypertensive arteries has been demonstrated, such changes may be secondary to a marked increase in cells showing nuclear polyploidy. Prolonged normalization of blood pressure in hypertensive animals can produce considerable regression of arterial changes toward the control state. The changes appear more marked with respect to the cellular rather than the extracellular abnormalities induced by hypertension. In man, little is known about the effects of antihypertensive therapy on the vasculature itself, although clinical complications related to both hemorrhagic or thrombotic strokes are clearly reduced by blood pressure reduction. On the other hand, the influence of treatment on the atherosclerotic process or on the course of coronary artery disease and its complications is not currently understood. The accelerating effect of hypertension on atherosclerosis generally requires a critical level of circulating lipoproteins. Enhanced atherosclerosis is not observed in hypertensive animals without hyperlipoproteinemia or in human subjects with low lipoprotein concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
Exp Mol Pathol 1984 Aug
PMID:Recent advances in molecular pathology. The effects of hypertension on the arterial wall. 638 Oct 89

Hereditary haemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomal dominant vascular disorder which associates epistaxis, mucocutaneous and visceral telangiectases, and recurrent haemorrhage with chronic anaemia and visceral shuntings. Recently, the tumour growth factor (TGF)-beta binding protein endoglin localized to 9q33-34 was identified as responsible for HHT in several large kindreds with pulmonary arteriovenous malformations (PAVMs). Additional linkage studies demonstrated that HHT is a genetically heterogeneous disorder with families unlinked to this region of 9q. In the families in which HHT was not linked to chromosome 9, less PAVMs were present. Furthermore, in one of these families, HHT was found linked to 3p22, where the TGF-beta II receptor is located. In this linkage study, we have analysed DNA from two families, in which HHT was unlinked to chromosome 9q and 3p, and PAVMs were absent, with a series of genetic markers on the centromeric region of chromosome 12. Using two-point linkage analysis, a significant lod score of Zmax = 7.86 at theta = 0.05 was obtained with the D12S85 microsatellite marker.
Hum Mol Genet 1995 May
PMID:A third locus for hereditary haemorrhagic telangiectasia maps to chromosome 12q. 763 56

Corticosteroids used orally and intravenously lead to lung diseases and vascular disorder. To investigate whether enolase levels are also changed by treatment with synthetic steroid dexamethasone (as alteration in the enolase levels have been correlated with lung cancer) we performed the following studies. A cDNA library was prepared from poly(A) mRNA extracted from human lung fibroblast cells. cDNA clone HLE1 containing 1.7 kb insert coding for enolase was isolated. Its identity was confirmed by (a) translation of the hybrid selected mRNA and (b) nucleotide sequence analysis of the insert and comparison with known enolase sequences from other species. The lung enolase is coded by a polypeptide of 458 amino acid residues (mr = 49.5 kD). Nucleotide sequencing and derived amino acid sequence data suggest that the cloned enolase is non-neuronal isoform of enolase (NNE). In lung fibroblast cells, dexamethasone caused remarkable increase in the abundance of the enolase mRNA, which was concentration and time dependent. The induction by dexamethasone required de novo RNA synthesis but not de novo protein synthesis.
Biochem Mol Biol Int 1993 Jun
PMID:Human lung enolase: cloning and sequencing of cDNA and its inducibility with dexamethasone. 768 84

We have investigated the effect of genotypes of apolipoprotein E (ApoE) on the pathologies found in Alzheimer's disease (AD) and its related gene expression in 38 aged human brains obtained from consecutive autopsied cases. ApoE2/3, -3/3, -3/4, and -4/4 were typed in those aged brains, with ApoE3/3 being most prevalent. The AD pathologies were undetectable in ApoE2/3 brains, but were frequently observed in the other ApoE groups. In ApoE3/3 brains, 55%, 34%, and 24% of the cortical sections examined showed senile plaques (SPs), neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA), respectively. In ApoE4/4 brains, the SP formation was significantly higher. The ApoE genotype neither affected ApoE, APP, or tau mRNA level, nor the differential expression of the latter two. These results suggest that ApoE4/4 accelerates and ApoE2/3 decelerates the development of the AD pathologies in the aged brain, but this is not through alterations of the APP and tau gene expression.
Brain Res Mol Brain Res 1995 Mar
PMID:Apolipoprotein E genotype, Alzheimer's pathologies and related gene expression in the aged population. 777 5

We evaluated the efficacy of murine monoclonal antibodies (MAbs) targeted to the A beta amyloid of Alzheimer's disease for development of procedures for the in vivo identification of amyloid angiopathy (AA). MAbs to A beta were prepared and screened for effectiveness in visualizing AA and neuritic plaques in postmortem AD brain sections. They were assessed again after enzymatic cleavage to produce Fab fragments and after labeling with technetium-99m (99mTc) using a diamide dimercaptide ligand system. Modified and radiolabeled Fab fragments retained activity and specificity toward amyloid-laden blood vessels and neuritic plaques. A highly specific murine MAb, 10H3, was identified and characterized that fulfills criteria necessary for the development of an in vivo diagnostic imaging agent. Toxicity studies in rats showed the MAb to be safe. Biodistribution studies in mice demonstrated desirable properties for use as an imaging agent. Expansion and adaptation of these strategies may provide the methods and materials for the noninvasive analysis of AA in living patients, and permit assessment of the contribution of AA to the clinical and pathological features of AD.
Mol Neurobiol
PMID:Development of an anti-A beta monoclonal antibody for in vivo imaging of amyloid angiopathy in Alzheimer's disease. 788 86

Amyloid plaques, associated with argyrophilic dystrophic neurites, and cerebral amyloid angiopathy (CAA), but no neurofibrillary tangles, were found in the brains of three middle-aged marmoset monkeys that had been injected intracerebrally (ic) 6-7 yr earlier with brain tissue from a patient with early-onset Alzheimer's disease. Such changes were not found in the brains of three age-matched control marmosets. Immunochemically the amyloid plaques and CAA stained with antibody to beta (A4)-protein. The plaques and CAA displayed dichroic birefringence when stained with Congo red and viewed under polarized light. beta (A4)-amyloid plaques and CAA were also found in the brain of one of two marmosets injected ic 6 yr previously with brain tissue from a patient with prion disease with concomitant beta (A4)-amyloid plaques and CAA. An occasional beta (A4)-amyloid plaque was found in the brains of two of four marmosets injected ic > 4.5 yr previously with brain tissue from three elderly patients, two of whom had suspected (but untransmitted) CJD. No beta (A4)-amyloid plaques or CAA were found in six marmosets who were older than the injected animals, in four marmosets that had not developed spongiform encephalopathy (SE) having been injected several years previously with human brain tissue from three younger patients with suspected or atypical prion disease, or in 10 younger marmosets who had undergone various neurosurgical procedures. Seventeen marmosets injected in the same way with brain tissue from patients or animals with SE developed SE 17-49 mo after injection. These results suggest that beta (A4)-amyloidosis is a transmissible process comparable to the transmissibility of SE.
Mol Neurobiol 1994 Feb
PMID:Induction of beta (A4)-amyloid in primates by injection of Alzheimer's disease brain homogenate. Comparison with transmission of spongiform encephalopathy. 808 26

The polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) are a family of low molecular weight organic cations that play essential intracellular regulatory roles in cell growth and differentiation. Consistent with this important function, increases in cellular polyamine contents are necessary for a variety of physiologic and pathologic events in the lung, including development of hypertensive pulmonary vascular disease secondary to chronic alveolar hypoxia. In intact rat lungs, hypoxia depresses ornithine decarboxylase activity, the initial rate-limiting enzyme in de novo polyamine synthesis, and enhances uptake of PUT from the vascular compartment, thus suggesting that increased polyamine transport is the driving mechanism behind hypoxia-induced increases in lung polyamine contents. Cultured bovine pulmonary artery smooth muscle cells (PASMCs) also express a transport system for SPD that is augmented by culture under hypoxic conditions. Because there may be multiple uptake pathways that are relatively selective for specific polyamines, the present study determined whether cultured bovine PASMCs expressed discrete transporters for [14C]PUT, [14C]SPD, and [14C]SPM, and whether they were differentially regulated by hypoxia. [14C]PUT, [14C]SPD, and [14C]SPM transport was examined in PASMCs cultured under "standard" (culture medium PO2: > 100 torr), "normoxic" (culture medium PO2: 50 to 70 torr), or "hypoxic" (culture medium PO2: 18 to 30 torr) conditions. Uptake of all three [14C]polyamines in cells cultured under standard conditions was temperature- and concentration-dependent, exhibited saturation kinetics, and could be modeled by Michaelis-Menten kinetics. In hypoxic PASMCs, values of Vmax for PUT, SPD, and SPM uptake increased by 3-, 2-, and 2-fold, respectively, relative to cells cultured under normoxic or standard incubator conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Feb
PMID:Multiple polyamine transport pathways in cultured pulmonary artery smooth muscle cells: regulation by hypoxia. 811 Apr 72

The present study utilized the monocrotaline (MCT) model of pulmonary hypertension in rats to examine temporal alterations in steady-state levels of basement membrane (BM) component mRNA and deposition of protein using Northern analysis and immunohistochemistry, respectively. MCT (60 mg/kg, subcutaneous) produced sustained increases in lung dry tissue mass by 7 days, right ventricular mass by 14 days, and pulmonary arterial pressure by 21 days after administration. mRNA levels specific for laminin (LM) were elevated as early as 1 day after MCT treatment, while mRNA for all BM components examined except type IV collagen were increased in lungs from MCT-treated rats by day 4. Differences in LM, perlecan (PN), and type IV collagen-specific mRNAs from lung tissue between MCT-treated and control rats disappeared by day 14. In contrast, fibronectin (FN) mRNA remained elevated in lung tissue from MCT-treated rats from day 4 onward. Increases in immunolocalizable FN and LM in the vasculature, and PN and type IV collagen in gas exchange areas, were observed 4 days after MCT treatment compared with controls. These changes generally became more pronounced by 21 days after MCT administration, at which time the parenchyma of MCT-treated rats also demonstrated increases in immunolocalizable FN, LM, and BM-chondroitin sulfate proteoglycan (BM-CSPG). The pulmonary vasculature additionally showed increases in type IV collagen, PN, and BM-CSPG in MCT-treated rats compared with controls by 21 days. These observations suggest that the accumulation of specific BM components in the pulmonary vasculature and parenchyma may contribute to the pathogenesis and maintenance of MCT-induced hypertensive pulmonary vascular disease.
Am J Respir Cell Mol Biol 1993 Oct
PMID:Temporal alterations in specific basement membrane components in lungs from monocrotaline-treated rats. 839 80

Recent advances indicate soluble amyloid beta (A beta) protein is produced constitutively during normal metabolism of the amyloid precursor protein (APP). This has not been directly examined in human brain vascular tissues. Using a panel of well-characterized antibodies, here we show that increased amounts of soluble A beta were found in isolated vascular tissues from AD subjects compared to age-matched controls without significant Alzheimer pathology. Immunocytochemical analyses of isolated vessel preparations showed characteristic transverse patterns of A beta deposits in large vessels with smooth muscle, however, fine A beta deposits were apparent even in capillaries. A proportion of such A beta protein and potentially amyloidogenic carboxyl terminal fragments were released by solubilization and disruption of the vascular basement membrane by collagenase treatments. We further demonstrated by in vitro metabolic labelling that soluble A beta or an A beta-like peptide is associated and produced by cerebral microvessels, meningeal vessels and the choroid plexus isolated postmortem from human as well as rat brain. Compared to those from young rats, cerebral microvessels from aging rats showed increased release of carboxyl terminal fragments of APP and A beta-like peptide. Our observations provide the first direct demonstration that human vascular tissues produce soluble A beta, a product of the secretory pathway in APP processing. Our findings also suggest that aging associated alterations in the basement membranes are a factor in A beta accumulation that results in vascular amyloid deposition, the principal feature of cerebral amyloid angiopathy.
Brain Res Mol Brain Res 1996 Jan
PMID:Production and increased detection of amyloid beta protein and amyloidogenic fragments in brain microvessels, meningeal vessels and choroid plexus in Alzheimer's disease. 871 40

Recombinant mouse (Mus musculus) and rat (Rattus norvegicus) cystatin C were produced by expression in Escherichia coli, isolated and functionally characterized. The mouse and rat inhibitors were both fully active in titrations of papain. Determination of equilibrium constants for dissociation (Ki) for their complexes with the target proteinase, cathepsin B, produced values not largely different from that for human cystatin C (Ki 0.07-0.13 nM). Rabbit antisera against mouse and rat cystatin C were produced and used for improved affinity purification of the recombinant inhibitors. Affinity purified immunoglobulins isolated from the antiserum against mouse cystatin C were used for construction of a sensitive enzyme-linked immunosorbent assay. The assay was used to demonstrate a high degree of immunological cross-reactivity between mouse and rat cystatin C and could be used for cystatin C quantification in mouse and rat tissue homogenates. All tissues analyzed contained cystatin C, with a relative content very similar to that of human tissues. For all species, brain tissue contained the highest cystatin C amounts and liver the lowest, whereas kidney, spleen and muscle tissues were intermediate in content. In the mouse, a notable high cystatin C content in parotid gland tissue was observed. The high degree of similarity in distribution pattern and functional properties for mouse, rat and human cystatin C indicates that a murine model should be relevant for studies of the human disease, hereditary cystatin C amyloid angiopathy.
Comp Biochem Physiol B Biochem Mol Biol 1996 Jul
PMID:Mouse and rat cystatin C: Escherichia coli production, characterization and tissue distribution. 876 Nov 77


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