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

Immunocytochemistry of muscarinic receptors on human heart biopsies from patients with heart disease was studied using rabbit antibodies against a synthetic peptide corresponding to amino acids 168-192 of the second extracellular loop of the human M2 muscarinic receptor. By using both light and electron microscopic immunocytochemistry techniques, muscarinic receptors were visualized on sarcolemma of human myocytes from patients with different heart diseases such as coronary heart disease and dilated cardiomyopathy in adults and congenital heart disease in children. The patchy distribution of immunoreactivity suggests a muscarinergic activity in vivo. These reactivities were abolished by preincubation of antibodies with antigenic peptide and were not shown in the absence of antibodies. Moreover, these antibodies were able to interfere with muscarinic ligand binding in myocardium from human dilated cardiomyopathy as shown by decreases in binding sites and antagonist affinity. These results demonstrate that the antibodies against the second extracellular loop of the human M2 muscarinic receptor can specifically recognize muscarinic receptors in human tissue and display pharmacological activity in human diseased myocardium, confirming their usefulness for the study of localization and function of muscarinergic activity in the human heart.
J Mol Cell Cardiol 1995 Aug
PMID:Localization of muscarinic receptors in human heart biopsies using rabbit anti-peptide antibodies. 852 36

Vitamin B6 is effective in the treatment of carpal tunnel syndrome and related disorders in patients with vitamin B6 deficiency. Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with deficiencies of vitamin B6, folate, and cobalamin. Patients who were given vitamin B6 for carpal tunnel syndrome and other degenerative diseases were found to have 27% of the risk of developing acute cardiac chest pain or myocardial infarction, compared with patients who had not taken vitamin B6. Among elderly patients of the author (JE) expiring at home, the average age at death from myocardial infarction was 8 years later in those who had taken vitamin B6, compared with those who had not taken vitamin B6. The preventive effect of vitamin B6 on progression of coronary heart disease may be related to increased formation of pyridoxal phosphate, the coenzyme that is required for catabolism of the atherogenic amino acid, homocysteine.
Res Commun Mol Pathol Pharmacol 1995 Aug
PMID:Prevention of myocardial infarction by vitamin B6. 855 75

The metabolites of linoleic (LA) and alpha-linolenic (ALA) acids are involved in coronary heart disease. Both n-6 and n-3 essential fatty acids (EFAs) are likely to be important in prevention of atherosclerosis since the common risk factors are associated with their reduced 6-desaturation. We previously demonstrated the ability of heart tissue to desaturate LA. In this study we examined the ability of cultured cardiomyocytes to metabolize both LA and ALA in vivo, in the absence and in the presence of gamma linolenic acid (GLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) alone or combined together. In control conditions, about 25% or LA and about 90% of ALA were converted in PUFAs. GLA supplementation had no influence on LA conversion to more unsaturated fatty acids, while the addition of n-3 fatty acids, alone or combined together, significantly decreased the formation of interconversion products from LA. Using the combination of n-6 and n-3 PUFAs, GLA seemed to counterbalance partially the inhibitory effect of EPA and DHA on LA desaturation/elongation. The conversion of ALA to more unsaturated metabolites was greatly affected by GLA supplementation. Each supplemented fatty acid was incorporated to a significant extent into cardiomyocyte lipids, as revealed by gas chromatographic analysis. The n-6/n-3 fatty acid ratio was greatly influenced by the different supplementations; the ratio in GLA+EPA+DHA supplemented cardiomyocytes was the most similar to that recorded in control cardiomyocytes. Since important risk factors for coronary disease may be associated with reduced 6-desaturation of the parent EFAs, administration of n-6 or n-3 EFA metabolites alone could cause undesirable effects. Since they appear to have different and synergistic roles, only combined treatment with both n-6 and n-3 metabolites is likely to achieve optimum results.
Mol Cell Biochem
PMID:Metabolism of linoleic and alpha-linolenic acids in cultured cardiomyocytes: effect of different N-6 and N-3 fatty acid supplementation. 873 49

There is evidence that flavonoid intake correlates inversely with coronary heart disease risk. Flavonoids are widely distributed in food and drinks and act as antioxidants and iron chelators. The aim of this study was to determine whether pycnogenol (a flavonoid extracted from the bark of Pinus pinaster) and catechin could minimise the myocardial mitochondrial damage due to ischemia/reperfusion. Using the rat heart model of ischemia/reperfusion we found that pycnogenol had no significant effect on the resultant damage, while catechin suppressed the observed elevation of low molecular weight iron during ischemia/reperfusion which might explain the significantly reduced mitochondrial injury when using catechin in the perfusate. Our results suggest that some flavonoids might be effective in minimizing ischaemic/reperfusion injury and would require further detailed investigation.
Res Commun Mol Pathol Pharmacol 1996 Jan
PMID:Effect of flavonoids on the outcome of myocardial mitochondrial ischemia/reperfusion injury. 882 32

Low density lipoproteins (LDL) in patients with coronary atherosclerosis have a substantially lower content of sialic acid when compared with the LDL from healthy subjects. Desialylated LDL have smaller sizes and greater electrophoretic mobilities than sialylated ones. Desialylated LDL may be responsible for the accelerated development of foam cells in atherosclerosis. In the present study, we investigated a relationship between the electrophoretic mobility of lipoproteins and the number of significantly obstructed vessels in patients with coronary heart disease (CHD). Our findings indicate that when the number of significantly obstructed vessels is increased, the electrophoretic mobility of lipoproteins is high. We also investigated the possible role of serum sialidase activity on lipoprotein desialylation in patients with coronary heart disease. In patients with single vessel disease (p < 0.01) and double-triple vessel disease (p < 0.001) the mean serum sialidase activity was significantly higher than in the control group.
Res Commun Mol Pathol Pharmacol 1996 Jan
PMID:The relationship between the electrophoretic mobility of lipoproteins and coronary heart disease. 882 36

Human heart matrix metalloproteinases (MMP) are present in the latent form and activated in the failing heart. To examine whether the MMP activation was due to gene and/or post-translational modification, we analysed tissue from 10 explanted hearts due to coronary heart disease (CHD) and five normal left atrial tissue from donor hearts. Based on in situ immunolabeling MMP-1, tissue inhibitor of metalloproteinase (TIMP-1) and collagen were co-localized in the interstitial tissue. Based on sandwich ELISA, TIMP-1 and MMP-1 levels were 37 +/- 8 ng/mg and 9 +/- 2 ng/mg in normal tissue (P < 0.01) and 12 +/- 5 ng/mg and 75 +/- 11 ng/mg in the infarcted tissue (P < 0.01), respectively. These levels suggest repression of TIMP-1 during myocardial infarction. Northern blot analysis indicated that the mRNAs for both MMP-1 and TIMP-1 were increased three-to four-fold in the infarcted tissue as compared to the normal tissue, suggesting upregulation of MMP and TIMP gene transcription following infarction. Based on in situ tissue overlay zymography, the generalized activation of MMP was observed in the interstitium of the infarcted heart. Zymographic and immunoblot analysis demonstrated the presence of one band at 66 kDa (MMP-2) in the normal tissue and several bands at 92 (MMP-9), 66 (MMP-2) and 54 kDa (MMP-1) in the infarcted heart. Incubation of the zymographic gel with metal chelator (phenanthroline) abolished bands at 92 kDa and 54 kDa but phenanthroline did not abolish the lytic band at 66 kDa. The 66 kDa band was completely abolished in the presence of phenanthroline and phenyl methyl sulfonyl fluoride (PMSF). 2D-zymographic analysis suggested that the lytic band at 66 kDa was a mixture of two neutral proteinases with different isoelectric point. Plasminogen/gelatin zymographic analysis of infarcted tissue extract indicated that the band at 66 kDa was plasmin generated due to increased expression of tissue plasminogen activator (tPA) activity. In relation to increased expression of gelatinase in the infarcted tissue, our data suggest that gelatinase B (92 kDa) is induced in diseased heart. The results suggest that tPA converts plasminogen to plasmin which, in turn, activates MMPs and inactivates TIMP-1 post-translationally following ischemic cardiomyopathy.
J Mol Cell Cardiol 1996 Jul
PMID:Post-transcriptional regulation of extracellular matrix metalloproteinase in human heart end-stage failure secondary to ischemic cardiomyopathy. 884 29

Previous association studies between angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) polymorphisms and several cardiovascular diseases have reported variable results. Therefore we examined the association of the DNA variants of ACE and AGT with early, severe coronary heart disease (CHD). In addition, we compared the genotypes of both polymorphisms and the recently discovered polymorphism in the E-selectin gene in both patients and an unselected population. This study included 113 patients with severe CHD (50 years old or less) and up to 197 control subjects. The frequencies of the ACE I/D variants were 48% I and 52% D in the controls and 46% I and 54% D in the patients. The frequencies of the AGT-M235T polymorphism were 60.8% M and 39.2% T in controls and 49.1% M and 50.9% T in the patients. The frequencies of the S128R polymorphism of the E-selectin were 91.3% S and 8.7% R in controls and 84.5% S and 15.5% R in the patients. In our studies the DD genotype of ACE was not associated with early severe CHD. We found a correlation between the M235T molecular variant of AGT and the S128R variant of E-selectin to early severe CHD.
J Mol Med (Berl) 1997 Jan
PMID:Relationship of polymorphisms in the renin-angiotensin system and in E-selectin of patients with early severe coronary heart disease. 902 Mar 85

We are just beginning to uncover the genetic determinants of coronary heart disease. The genotype-phenotype associations are complex as a consequence of pleiotropy, variation with age, selection owing to the high lethality of the disease, and interactions between genes and with environmental factors. Nevertheless, identification of the gene variants involved in the chronic and acute processes of coronary heart disease appears possible; this could considerably improve our understanding of the aetiology and mechanisms of this disease. Simultaneous analysis of several predisposing alleles should provide the means to identify high-risk individuals and to adapt therapeutic approaches to the genetic make-up of patients.
Mol Med Today 1997 May
PMID:Coronary heart disease and genetics in epidemiologist's view. 917 82

The Keewatin Inuit of the Northwest Territories of Canada have a very low age-adjusted mortality rate from coronary heart disease. We hypothesized that this apparent protection from disease has a genetic basis. We determined the prevalence of the disease-associated alleles of five candidate genes for atherosclerosis-related phenotypes. Surprisingly, four of the five alleles studied, namely AGT T235, FABP2 T54, PON R192 and APOE E4, were significantly more frequent in a sample of 175 Keewatin Inuit than among a representative control sample of whites living in the region. The high frequencies of these disease-associated alleles suggests either that they have no relationship with disease susceptibility in the Inuit, or that some unmeasured genetic and/or environmental factors mitigate disease susceptibility that is associated with these alleles. This highlights the difficulty in extrapolating findings from one population to another. Also, very modest genotype-phenotype associations were observed between APOE genotype (P = 0.016) and plasma low-density lipoprotein cholesterol concentration and between FABP2 genotype and plasma 2-h postprandial, glucose concentration (P = 0.048). The relationship between APOE alleles and plasma low-density lipoprotein cholesterol was the same as has been previously reported in many study samples. However, the relationship between FABP2 alleles and plasma 2-h postprandial glucose concentrations was the opposite to that reported in other studies. This suggests that differences in environment, such as the type of fatty acid consumed, interacts with functional differences in gene products involved in candidate metabolic pathways to produce phenotypic differences.
J Mol Med (Berl) 1997 May
PMID:Are Canadian Inuit at increased genetic risk for coronary heart disease? 918 78

Angiotensin II (Ang II), the effector peptide of the renin-angiotensin system (RAS), regulates volume and electrolyte homeostasis and is involved in cardiac and vascular cellular growth in humans and other species. This system, which has been conserved throughout evolution, plays an important role in cardiac and vascular pathology associated with hypertension, coronary heart disease, myocarditis and congestive heart failure. The traditional RAS is viewed as a system in which circulating Ang II is delivered to target organs and cells. However, in the past decade, a local RAS has been described in cardiac cells, providing evidence for autocrine and paracrine pathways by which biological actions of Ang II could be mediated. The critical actions of Ang II are mediated primarily through the AT1, G-protein (guanylyl nucleotide binding protein) coupled receptor. In addition to coupling to conventional G-protein signal transduction pathways, the AT1 receptor was recently shown to increase the tyrosine phosphorylation of several intracellular substrates, including the STAT (Signal Transducers and Activators of Transcription) family of novel transcription factors, in rat cardiac fibroblasts, myocytes and vascular smooth muscle cells, and AT1 receptor transfected CHO cells. It has been shown that Ang II stimulates the tyrosine phosphorylation and nuclear translocation of Stat1 (Stat 91) and Stat3 (Stat 92). Angiotensin II acting directly through the AT1 receptor, induces the formation of a complex of STAT proteins termed SIF (sis-inducing factor) which binds the DNA sequence, SIE (sis-inducing element) present in the promotor element of many genes. This provides evidence for a direct role of Ang II in mediating inflammatory and remodeling responses through the JAK-STAT pathway. Thus, it is likely that the JAK-STAT pathway has an important role in Ang II-mediated effects on gene transcription, cardiac and vascular cellular growth/development, and inflammatory responses.
J Mol Cell Cardiol 1997 Nov
PMID:Molecular mechanisms of angiotensin II in modulating cardiac function: intracardiac effects and signal transduction pathways. 940 64


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