Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor gamma ANP, that is gamma ANP-(1-25), and alpha ANP [gamma ANP-(99-126)], we studied the secretion of gamma ANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected gamma ANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 +/- 62 (+/- SE) pg/mL (174 +/- 21 pmol/L)]; the mean plasma alpha ANP-LI level at the same time in these subjects was 32.8 +/- 4.4 pg/mL (10.7 +/- 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was alpha ANP, and the other was the 10K N-terminal gamma ANP fragment (N-peptide) resulting from the removal of alpha ANP (3K) from gamma ANP (13K). In addition, gamma ANP (13K), which possessed both gamma ANP-(1-25)-LI and alpha ANP-LI, and beta ANP, an antiparallel dimer of alpha ANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal gamma ANP fragment and alpha ANP (P less than 0.01) and almost equal step-ups in the coronary sinus plasma levels of the N-terminal gamma ANP fragment and alpha ANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI (17.4 +/- 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 +/- 7.1; P less than 0.01) suggest the slower clearance of the N-terminal gamma ANP fragment than alpha ANP and a role for the kidney in its degradation. Since the molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI in patients with cirrhosis (20.7 +/- 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal gamma ANP fragment is metabolized by the liver. In patients with heart disease, plasma gamma ANP-(1-25)-LI and alpha ANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal gamma ANP fragment and alpha ANP in response to atrial stretch.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gamma-atrial natriuretic polypeptide (gamma ANP)-derived peptides in human plasma: cosecretion of N-terminal gamma ANP fragment and alpha ANP. 297 Apr 70

Disease-associated amyloid deposits contain both fibrillar and nonfibrillar components. The majority of these amyloid components originate or coexist in the bloodstream. To understand the nature of the interaction between the nonfibrillar and fibrillar components, we have developed a centrifugation method to isolate fibril binding proteins from human serum. Amyloid fibrils composed of either Abeta peptide or apolipoprotein C-II (apoC-II) cosedimented with specific serum proteins. Gel electrophoresis, mass spectrometry peptide fingerprinting, and Western analysis identified the major binding species as proteins found in HDL particles, including apoA-I, apoA-II, apoE, clusterin, and serum amyloid A. Sedimentation analysis showed that purified human HDL and recombinant apoA-I lipid particles bound directly to Abeta and apoC-II amyloid fibrils. These studies reveal a novel function of HDL that may contribute to the well-established protective effect of this lipoprotein class in heart disease.
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PMID:High density lipoproteins bind Abeta and apolipoprotein C-II amyloid fibrils. 1643 77

Galphaq, encoded by the human GNAQ gene, is an effector subunit of the Gq heterotrimeric G-protein and the convergence point for signaling of multiple Gq-coupled neurohormonal receptors. To identify naturally occurring mutations that could modify GNAQ transcription, we examined genomic DNA isolated from 355 normal subjects for genetic variants in transcription factor binding motifs. Of seven variants identified, the most common was a GC to TT dinucleotide substitution at -694/-695 (allele frequency of 0.467 in Caucasians and 0.329 in African Americans) within a GC-rich domain containing consensus binding sites for Sp-1, c-rel and EGR-1. In promoter-reporter analyses, the TT substitution increased promoter activity in cultured neonatal rat cardiac myocytes and human HEK fibroblasts by approximately 30% at baseline and after stimulation with phorbol ester. Two other relatively common polymorphisms, -173G/A and -168G/A, did not affect promoter activity. Since altered expression/activity of Galphaq is implicated in heart disease, we re-sequenced the GNAQ promoter in 1052 prospectively followed heart failure patients. The TT variant was not increased in heart failure, but was associated with decreased survival time among African Americans, with an adjusted RR of death/cardiac transplant of 1.95 (95% CI = 1.21-3.13) for heterozygotes and 2.4 (95% CI = 1.36-4.26) for homozygotes. Gel mobility shift assays showed that this GC/TT substitution eliminated Sp-1 binding without affecting c-rel or EGR-1 binding to this promoter fragment. Thus, the GNAQ -694/-695 promoter polymorphism alters transcription factor binding, increases promoter activity and adversely affects outcome in human heart failure.
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PMID:A functional polymorphism of the Galphaq (GNAQ) gene is associated with accelerated mortality in African-American heart failure. 1772 Sep 80

The insulin-like growth factor-II/mannose 6-phosphate receptor (IGF2R) over-expression correlates with heart disease progression. The IGF2R is not only an IGF2 clearance receptor, but it also triggers signal transduction, resulting in cardiac hypertrophy, apoptosis and fibrosis. The present study investigated the nuclear factor IL-3 (NFIL3), a transcription factor of the basic leucine zipper superfamily, and its potential pro-survival effects in cardiomyocytes. NFIL3 might play a key role in heart development and act as a survival factor in the heart, but the regulatory mechanisms are still unclear. IGF2 and IGF2R protein expression were highly increased in rat hearts subjected to hemorrhagic shock. IGF2R protein expression was also up-regulated in H9c2 cells exposed to hypoxia. Over-expression of NFIL3 in H9c2 cardiomyoblast cells inhibited the induction of hypoxia-induced apoptosis and down-regulated IGF2R expression levels. Gel shift assay, double-stranded DNA pull-down assay and chromatin immune-precipitation analyses indicated that NFIL3 binds directly to the IGF2R promoter region. Using a luciferase assay, we further observed NFIL3 repress IGF2R gene promoter activity. Our results demonstrate that NFIL3 is an important negative transcription factor, which through binding to the promoter of IGF2R, suppresses the apoptosis induced by IGF2R signaling in H9c2 cardiomyoblast cells under hypoxic conditions.
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PMID:NFIL3 suppresses hypoxia-induced apoptotic cell death by targeting the insulin-like growth factor 2 receptor. 2553 74