Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present investigation was designed to evaluate whether end-stage cardiac failure in patients affected by dilated cardiomyopathy (DC) was dependent upon extensive myocyte cell death with reduction in muscle mass or was the consequence of collagen accumulation in the myocardium independently from myocyte cell loss. In addition, the mechanisms of ventricular dilation were analysed in order to determine whether the changes in cardiac anatomy were important variables in the development of intractable congestive heart failure. DC is characterized by chamber dilation, myocardial scarring and myocyte hypertrophy in the absence of significant coronary atherosclerosis. However, the relative contribution of each of these factors to the remodeling of the ventricle is currently unknown. Moreover, no information is available concerning the potential etiology of collagen deposition in the myocardium and the changes in number and size of ventricular myocytes with this disease. Morphometric methodologies were applied to the analysis of 10 DC hearts obtained from patients undergoing cardiac transplantation. An identical number of control hearts was collected from individuals who died from causes other than cardiovascular diseases. DC produced a 2.2-fold and 4.2-fold increase in left ventricular weight and chamber volume resulting in a 48% reduction in mass-to-volume ratio. In the right ventricle, tissue weight and chamber size were both nearly doubled. Left ventricular dilation was the result of a 59% lengthening of myocytes and a 20% increase in the transverse circumference due to slippage of myocytes within the wall. Myocardial scarring represented by segmental, replacement and interstitial fibrosis occupied approximately 20% of each ventricle, and was indicative of extensive myocyte cell loss. However, myocyte number was not reduced and average cell volume increased 2-fold in both ventricles. In conclusion, reactive growth processes in myocytes and architectural rearrangement of the muscle compartment of the myocardium appear to be the major determinants of ventricular remodeling and the occurrence of cardiac failure in DC.
J Mol Cell Cardiol 1995 Jan
PMID:The cellular basis of dilated cardiomyopathy in humans. 776 Mar 53

To assess the direct effect of androgen on the development of atherosclerosis, we investigated the effect of androgen and its receptor expression in rat vascular smooth muscle cells (VSMC) isolated from rat aorta. We detected the androgen receptor mRNA in VSMC by reverse transcription of the total RNA coupled with amplification of the resulting cDNA by polymerase chain reaction. Binding studies revealed the presence of a single class of binding sites for testosterone (Kd 7.37 nM, Bmax 10.59 fmol/mg protein) and dihydrotestosterone (DHT; Kd 4.89 nM, Bmax 11.37 fmol/mg protein) in VSMC. Measurement of 5 alpha-reductase activity suggested that testosterone is converted to DHT in VSMC (Km 0.36 microM, Vmax 623 fmol/mg protein/h). Moreover, in the present study, DHT significantly stimulated DNA synthesis of VSMC (120-160% of control). The mitogenic activity of testosterone is much less potent than that of DHT. Considering these results, we concluded that androgen may directly accelerate atherosclerosis by stimulating the proliferation of VSMC.
J Steroid Biochem Mol Biol 1994 Aug
PMID:Androgen receptors, 5 alpha-reductase activity and androgen-dependent proliferation of vascular smooth muscle cells. 804 46

We report the cloning of a 3656-bp cDNA encoding a putative human very low density lipoprotein (VLDL)/apolipoprotein E (ApoE) receptor. The gene encoding this protein was mapped to chromosome 9pter-p23. Northern analysis of human RNA identified cognate mRNAs of 6.0 and 3.8 kb with most abundant expression in heart and skeletal muscle, followed by kidney, placenta, pancreas, and brain. The pattern of expression generally paralleled that of lipoprotein lipase mRNA but differed from that of the low density lipoprotein (LDL) receptor and the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP), which are members of the same gene family. VLDL/ApoE receptor message was not detected in liver, whereas mRNAs for both LDL receptor and LRP were found in hepatic tissue. In mouse 3T3-L1 cells, VLDL/ApoE receptor mRNA was induced during the transformation of the cells into adipocytes. Expression was also detected in human choriocarcinoma cells, suggesting that at least part of the expression observed in placenta may be in trophoblasts, cells which would be exposed to maternal blood. Expression in brain may be related to high levels of ApoE expression in that organ, an observation of potential relevance to the recently hypothesized role for ApoE in late onset Alzheimer disease. Our results suggest that the putative VLDL/ApoE receptor could play a role in the uptake of triglyceride-rich lipoprotein particles by specific organs including striated and cardiac muscle and adipose tissue and in the transport of maternal lipids across the placenta. The findings presented here, together with recent observations from other laboratories, bring up the possibility that a single gene, the VLDL/ApoE receptor, may play a role in the pathogenesis of certain forms of atherosclerosis, Alzheimer disease, and obesity.
Somat Cell Mol Genet 1993 Nov
PMID:Cloning of a cDNA encoding a putative human very low density lipoprotein/apolipoprotein E receptor and assignment of the gene to chromosome 9pter-p23. 812 15

Calcium is a second messenger responsible for regulating a wide range of cellular processes. It is normally presented as brief spikes even in non-excitable cells. The necessity of limiting the period of calcium stimulation to brief bursts may depend upon the fact that prolonged elevation of calcium can be toxic. It can act on endonucleases in the nucleus to trigger programmed cell death. It will be argued that non-lethal effects of elevated calcium can lead to a variety of pathological conditions including hypertension, atherosclerosis, transformation, malignant hyperthermia and possible neural disorders such as spreading depression and manic-depressive illness.
Mol Cell Endocrinol 1994 Jan
PMID:The biology and medicine of calcium signalling. 814 20

The study of polymorphisms of human apolipoprotein AI/CIII/IV gene cluster in the Moscow population was carried out using of methods of polymerase chain reaction and restriction. Polymorphisms of apolipoprotein AI/CIII/AIV gene cluster detected with SacI, PstI, PvuII, MspI have been investigated to search for their possible relation to the following quantitative lipid parameters: total cholesterol, HDL cholesterol, triglycerides, apolipoproteins AI, apolipoproteins B. It has been determined that in groups of individuals with increased cholesterol level the frequencies of uncommon alleles at the MspI, SacI, PvuII sites were significantly higher than in controls. Our results show that in groups with increased triglyceride level the frequency of uncommon alleles at the MspI and SacI sites was higher than in controls. Individuals with elevated apolipoprotein B and ratio of apolipoproteins B/AI > 1 have significantly higher frequency of uncommon alleles at the SacI and PvuII sites and uncommon alleles at the PvuII site, respectively. There was no statistically significant correlation between polymorphism at PstI site and lipid level variation. It has been established, by constructing DNA haplotypes, that the presence of particular haplotypes containing an uncommon allele at the PvuII and SacI sites, PvuII and MspI sites, MspI and SacI sites, PvuII and PstI sites, SacI and PstI sites is associated with lipid disorders, and may be associated with development of atherosclerosis.
Mol Biol (Mosk)
PMID:[Connection of polymorphic alleles of the gene cluster AI/CIII/AIV with disturbed lipid metabolism]. 814 52

The vasoactive peptides endothelin-1 (ET-1) and angiotensin-II (AII) have been implicated in chronic hypertension and may play important roles in related vascular diseases such as restenosis and atherosclerosis. Using a rat aortic smooth muscle (RASM) cell model, both ET-1 and AII induced concentration-dependent delayed increases in DNA synthesis relative to that in the serum-deprived controls. Stimulation of DNA synthesis was maximal at 100 nM for each peptide. All treatment of RASM cells resulted in a greater mitogenic effect (4- to 7-fold) than that observed for ET-1 (3-fold). When added in the presence of AII, ET-1 had a supplemental effect on DNA synthesis (5- to 10-fold above control). Although RASM cells expressed both ETA and AT1 receptors, radioligand binding experiments indicated that approximately 10-fold as many AT1 receptors as ETA receptors were present. In signal transduction studies, ET-1 and AII each elicited concentration-dependent increases in the intracellular Ca2+ concentration. ET-1 and AII also stimulated phosphoinositide metabolism and phosphorylation of a specific substrate for protein kinase-C. The release of total inositol phosphates in response to ET-1 and AII was concentration dependent and inhibited by the ETA receptor-selective antagonist BQ-123 and the AT1 receptor-selective antagonist losartan, respectively. In addition, tyrosine phosphorylation of 120- and 75-kilodalton proteins as well as the mitogen-activated protein kinases p44mapk and p42mapk was observed within 5 min of the addition of either ET-1 or AII. Taken together, these data indicate that ET-1 and AII may promote smooth muscle cell growth through common intracellular signaling mechanisms.
Mol Endocrinol 1994 Feb
PMID:Endothelin-1 and angiotensin-II stimulate delayed mitogenesis in cultured rat aortic smooth muscle cells: evidence for common signaling mechanisms. 817 Apr 71

Some peculiarities of the transcription of human genes with variable number of absolute tandem repeats in the coding region are discussed. The data on the association between short alleles of the apo(a) gene and atherosclerosis are analyzed. Data are described concerning the possible role of the MUC1 gene product, episialin, in carcinogenesis. The possible causes of the polydispersity of apo(a) and mucin gene transcripts are analyzed. It is supposed that RNA polydispersity is the result of the transcription of the repeat. The possible association between repeat transcription and recombination is discussed. The same inverse relationship is noted between the allele length (number of repeats) and the transcription level of the full gene for apo(a) and MUC1 genes. The possible role of the length of VNTR genes as risk factors of human pathogenesis is discussed.
Mol Biol (Mosk)
PMID:[Human genes, containing varying numbers of absolute tandem repeats in the coding area: the possible role in pathogenesis]. 818 60

Inbred mouse strains vary in susceptibility or resistance to dietary induced atherosclerosis. To investigate the effect of polyunsaturated fat feeding on postprandial serum cholesterol levels, in C57BL/67 (B6) and BALB/cJ inbred mice, we fed by stomach gavage previously fasted mice, a mixture containing 30% sunflower oil, 5% cholesterol, 2% sodium cholate and 0.5% choline chloride. The most significant difference in serum cholesterol levels between B6 and BALB/cJ mouse strains was observed at 2 h postfeeding. Susceptible B6 strain mice had a 41% postprandial increment in serum cholesterol. The resistant BALB/cJ strain had an insignificant 16% rise in serum cholesterol, at 2 h. We next examined eight other inbred mouse strains, to identify the gene(s) that regulate the observed 2 h postprandial hypercholesterolemia response, in the susceptible B6 mouse strain. Only the C57BR/cdJ and C57L/J strains developed postprandial hypercholesterolemia, at 2 h. The C57BR/cdJ strain had a 20% increase and the C57L/J strain a 62% increase in postprandial serum cholesterol levels. From this result, we found that the postprandial hypercholesterolemic response to an acute polyunsaturated fat-cholesterol feed, cosegregated with the a allele at the Gpd-1 and Ahd-1 loci, on mouse chromosome 4. In this study, non-responsiveness cosegregated with the b allele at the Gpd-1 and Ahd-1 loci. Thus polyunsaturated fat-cholesterol induced postprandial hypercholesterolemia appeared to be genetically determined by a gene located between the Gpd-1 and Ahd-1 loci, in mice. The putative gene regulating polyunsaturated fat-cholesterol induced post-absorptive hypercholesterolemia was designated Phc-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1994 Jan 12
PMID:Regulation of polyunsaturated fat induced postprandial hypercholesterolemia by a novel gene Phc-2. 819 Jan 22

The binding of fibrinogen to its receptor on mammalian platelets and avian thrombocytes has been extensively studied; and the receptors, composed of glycoproteins IIb and IIIa, have been characterized in both systems. Recently, monocytes have been implicated in the thrombotic complications of atherosclerosis, and in both the avian and human systems this appears to be through a procoagulant activity which leads to fibrinogen polymerization. Although fibrin polymerization by avian monocytes has been reported, the receptor for fibrinogen on these cells has not been reported previously. The present study describes the presence of glycoprotein IIb- and IIIa-like proteins in avian macrophages and correlates the localization of these glycoproteins with regions to which fibrinogen binds. Through the use of immunofluorescence light microscopy and immunogold electron microscopy in conjunction with monospecific, polyclonal antibodies, GPIIb and GPIIIa cross-reacting antigens were identified on membranes of monocyte/macrophages cultured from White Carneau pigeons. A specific concentration of the antigens was found on membrane ruffles and microvilli, sites to which FITC-labeled fibrinogen also bound. Interaction of the antibodies with pigeon macrophages was confirmed by enzyme-linked immunosorbent assays with cultured cells. Immunoblotting of membranes isolated from pigeon monocyte/macrophages identified a protein of 132,000 M(r) that was recognized by anti-GPIIb and a protein of 114,000 M(r) that was recognized by anti-GPIIIa. These pigeon monocyte glycoproteins comigrated with glycoproteins IIb and IIIa isolated from human platelets.
Exp Mol Pathol 1993 Oct
PMID:Glycoprotein IIb/IIIa cross-reacting antigen in monocyte-derived macrophages from the pigeon. 822 17

Elevated levels of plasma lipoprotein(a) [Lp(a)] have been correlated with the development of atherosclerosis in human populations. Apolipoprotein(a) [apo(a); the distinguishing protein component of Lp(a)] is characterized by multiple repeats of a sequence that closely resembles kringle IV of plasminogen. Variably-sized Lp(a) isoforms that are observed in the human population have been shown to occur as a result of differences in the numbers of the repeated kringle IV units in apo(a). Using PCR analysis of human liver mRNA, we have analyzed apo(a) from 10 unrelated individuals in order to determine the presence or absence of kringle IV repeat #1, and #30-#37. Based on the apo(a) cDNA sequence published for one individual, these kringles all differ to some degree in amino acid sequence from the major kringle IV repeat, which is present in a number of identically repeated copies. We found that sequences corresponding to apo(a) kringle IV repeat #1, and #30-#37 were present in all individuals studied. This suggests that the inverse relationship that has been observed between Lp(a) isoform size and plasma Lp(a) levels is mediated by different numbers of identical kringle IV repeats, by an as yet undetermined mechanism. During the course of this study, we identified a Met-->Thr polymorphism in the apo(a) kringle IV repeat #37. The calculated frequencies of the Met and Thr alleles were 0.58 and 0.42 respectively. We did not observe a correlation between the Met-->Thr substitution and either plasma Lp(a) levels, or apo(a) transcript size.
Hum Mol Genet 1993 Apr
PMID:The apolipoprotein(a) kringle IV repeats which differ from the major repeat kringle are present in variably-sized isoforms. 838 24


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