Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune hyperlipidemia (AIH) may be induced a variety of antibodies which inhibit different stages of the lipolytic process by which the lipid load is removed from the circulating lipoproteins. In a patient having a monoclonal gammopathy and a nephrotic syndrome with a glomerulonephritis and a marked hypertriglyceridemia, it was found previously that the monoclonal IgG gamma Lac. reacted with human VLDL as well as with human serum albumin. Here it is demonstrated that the purified IgG gamma inhibits the lipolysis of triglyceride substrates by reacting with a substance (Lac. S) necessary for lipoprotein lipase activity. The interaction of IgG lambda Lac. with serum or HDL-activated triglyceride substrates inhibits the lipolytic activity of human and rat plasma post heparin and also adipose tissue lipases. It slightly inhibits the activity of swine pancreatic lipases. The Lac S. which reacts with IgG Lac. is associated to whole and delipidated VLDL and HDL and not to LDL or purified APo-A. It may be an Apo-C or a non-peptidic co-factor of the lipases which remains bound to the apoprotein core after delipidation. Its lack of species specificity and its presence as traces in HSA preparations favors the latter hypothesis. The Lac. substances is different from the Pg and As substances which were found to react with IgA anti-Pg and IgG anti-As antibodies in previously reported antilipoprotein AIH.
Atherosclerosis 1977 Jan
PMID:Inhibition of lipoprotein lipase activity by a monoclonal immunoglobulin in autoimmune hyperlipidemia. 83 49

The utility of nonspecific polyclonal IgG for external imaging of experimental atherosclerosis was tested in a series of rabbits after balloon catheter deendothelialization of the abdominal aorta. Following injection of 111In-IgG, 111In-Fc, or 111In-Fab serial images were recorded. In addition, several animals received 125I-low density lipoproteins [125I-LDL], or 125I human serum albumin [125I-HSA] as positive and negative controls. Forty-eight hours after injection of the radiolabeled proteins, the aortas were removed, divided into abdominal and thoracic regions, counted, and autoradiographed. The images acquired after injection of 111In-IgG and 111In-Fc, showed clear focal accumulation of radioactivity in the healing abdominal aorta. In contrast, the images obtained after injection of 111In-Fab did not show focal radionuclide accumulation. For 111In-IgG and 111In-Fc there were three to six times as many counts in the abdominal as in the thoracic aorta, while for 111In-Fab and 125I HSA, the abdominal and thoracic counts were nearly equal. The results suggest that radiolabeled IgG and Fc can be used to image experimental atherosclerosis.
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PMID:Radionuclide imaging of experimental atherosclerosis with nonspecific polyclonal immunoglobulin G. 273 90

A pair of siblings with analbuminemia were followed for 38 years. The female patient received replacement therapy with human serum albumin. Extreme lipodystrophy developed in this patient by the fourth decade of life. She had juvenile osteoporosis, which normalized under albumin replacement. She died from a granulosa cell cancer at age 69. Her brother never received albumin, even though his serum contained only 60 micrograms/ml of an albumin-like protein. He suffered from severe osteoporosis with gibbus formation, and he died from a colon carcinoma at age 59. Despite high cholesterol values and high levels of several blood clotting factors, neither of the patients had severe atherosclerosis or thrombotic events. Laboratory findings before and after infusion of large amounts of albumin into the sister point to a mechanism whereby albumin-bound substances can be passively transported from the bloodstream into the extravascular space and vice versa.
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PMID:Bennhold's analbuminemia: a follow-up study of the first two cases (1953-1992). 862 84

Human serum albumin minimally-modified by methylglyoxal (MGmin-HSA) stimulated the synthesis and secretion of macrophage-colony stimulating factor (M-CSF) by mature human monocytes in vitro. Human serum albumin minimally-modified by glucose-derived advanced glycation endproducts (AGEmin-HSA) and human serum albumin highly-modified by glucose-derived advanced glycation endproducts (AGE-HSA) stimulated much lower secretion of M-CSF from human monocytes than did MGmin-HSA. MGmin-HSA and AGE-HSA but not AGEmin-HSA also stimulated the growth of human monocytic THP-1 cells in vitro which was inhibited by polyclonal antibodies to human M-CSF. For MGmin-HSA, the median growth stimulatory concentration EC50 value was 0.24 +/- 0.07 microM and the maximal increase in cell growth was 36% of control cell growth (n = 24). Similar induction of secretion of M-CSF from monocytes in vivo may contribute to atherosclerosis in macro- and micro-angiopathy, particularly in the development of diabetic complications.
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PMID:Synthesis and secretion of macrophage colony stimulating factor by mature human monocytes and human monocytic THP-1 cells induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts. 894 11

Human serum albumin minimally-modified by methylglyoxal (MGmin-HSA) stimulated the synthesis and secretion of tumour necrosis factor-alpha (TNF-alpha) from human monocytic THP-1 cells in vitro. Human serum albumin minimally-modified by glucose-derived advanced glycation endproducts (AGEmin-HSA) and human serum albumin highly-modified by glucose-derived advanced glycation endproducts (AGE-HSA) stimulated markedly lower synthesis and secretion of TNF-alpha from THP-1 cells than did MGmin-HSA. The median effective concentration EC50 value of MGmin-HSA for the secretion of TNF-alpha was 5.8 +/- 0.3 microM and the maximal secretion was 0.28 +/- 0.01 ng TNF-alpha/ml (n = 12) for incubations containing 5 x 10(5) cells/ml. MGmin-HSA (0.2-2.0 microM) also stimulated chemotaxis of THP-1 cells in vitro but AGE-HSA did not in this concentration range. The EC50 value of MGmin-HSA for the chemotactic response was 0.44 +/- 0.07 microM (n = 15). Similar induction of the synthesis and secretion of TNF-alpha and chemotaxis by monocytes in response to MGmin-HSA in vivo may contribute to atherosclerosis in macro- and micro-angiopathy, particularly in the development of chronic clinical complications of diabetes mellitus.
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PMID:Synthesis and secretion of tumour necrosis factor-alpha by human monocytic THP-1 cells and chemotaxis induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts. 929 94

The present report describes application of advanced analytical methods to establish correlation between changes in human serum proteins of patients with coronary atherosclerosis (protein metabolism) before and after moderate beer consumption. Intrinsic fluorescence, circular dichroism (CD), differential scanning calorimetry and hydrophobicity (So) were used to study human serum proteins. Globulin and albumin from human serum (HSG and HSA, respectively) were denatured with 8 m urea as the maximal concentration. The results obtained provided evidence of differences in their secondary and tertiary structures. The thermal denaturation of HSA and HSG expressed in temperature of denaturation (Td, degrees C), enthalpy (DeltaH, kcal/mol) and entropy (DeltaS kcal/mol K) showed qualitative changes in these protein fractions, which were characterized and compared with fluorescence and CD. Number of hydrogen bonds (n) ruptured during this process was calculated from these thermodynamic parameters and then used for determination of the degree of denaturation (%D). Unfolding of HSA and HSG fractions is a result of promoted interactions between exposed functional groups, which involve conformational changes of alpha-helix, beta-sheet and aperiodic structure. Here evidence is provided that the loosening of the human serum protein structure takes place primarily in various concentrations of urea before and after beer consumption (BC). Differences in the fluorescence behavior of the proteins are attributed to disruption of the structure of proteins by denaturants as well as by the change in their compactability as a result of ethanol consumption. In summary, thermal denaturation parameters, fluorescence, So and the content of secondary structure have shown that HSG is more stable fraction than HSA.
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PMID:Structure characterization of human serum proteins in solution and dry state. 1190 9

Accumulation of advanced glycation end products (AGEs) on tissue proteins increases with pathogenesis of diabetic complications and atherosclerosis. Here we examined the effect of peroxynitrite (ONOO(-)) on the formation of N( epsilon )-(carboxymethyl)lysine (CML), a major AGE-structure. When glycated human serum albumin (HSA; Amadori-modified protein) was incubated with ONOO(-), CML formation was detected by both enzyme-linked immunosorbent assay and high-performance liquid chromatography (HPLC) and increased with increasing ONOO(-) concentrations. CML was also formed when glucose, preincubated with ONOO(-), was incubated with HSA but was completely inhibited by aminoguanidine, a trapping reagent for alpha-oxoaldehydes. For identifying the aldehydes that contributed to ONOO(-)-induced CML formation, glucose was incubated with ONOO(-) in the presence of 2,3-diaminonaphthalene. This experiment led to identification of glucosone and glyoxal by HPLC. Our results provide the first evidence that ONOO(-) can induce protein modification by oxidative cleavage of the Amadori product and also by generation of reactive alpha-oxoaldehydes from glucose.
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PMID:Peroxynitrite induces formation of N( epsilon )-(carboxymethyl) lysine by the cleavage of Amadori product and generation of glucosone and glyoxal from glucose: novel pathways for protein modification by peroxynitrite. 1219 78

The accumulation of advanced oxidation protein products (AOPPs) has been linked to vascular lesions in diabetes, chronic renal insufficiency, and atherosclerosis. However, the signaling pathway involved in AOPPs-induced endothelial cells (ECs) perturbation is unknown and was investigated. AOPPs modified human serum albumin (AOPPs-HSA) bound to the receptor for advanced glycation end products (RAGE) in a dose-dependent and saturable manner. AOPPs-HSA competitively inhibited the binding of soluble RAGE (sRAGE) with its preferential ligands advanced glycation end products (AGEs). Incubation of AOPPs, either prepared in vitro or isolated from uremic serum, with human umbilical vein ECs induced superoxide generation, activation of NAD(P)H oxidase, ERK 1/2 and p38, and nuclear translocation of NF-kappaB. Activation of signaling pathway by AOPPs-ECs interaction resulted in overexpression of VCAM-1 and ICAM-1 at both gene and protein levels. This AOPPs-triggered biochemical cascade in ECs was prevented by blocking RAGE with either anti-RAGE IgG or excess sRAGE, but was not affected by the neutralizing anti-AGEs IgG. These data suggested that AOPPs might be new ligands of endothelial RAGE. AOPPs-HSA activates vascular ECs via RAGE-mediated signals.
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PMID:Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway. 1857 17

Lysophospholipids play important roles in cellular signal transduction and are implicated in many biological processes, including tumorigenesis, angiogenesis, immunity, atherosclerosis, arteriosclerosis, cancer and neuronal survival. The intracellular transport of lysophospholipids is through FA (fatty acid)-binding protein. Lysophospholipids are also found in the extracellular space. However, the transport mechanism of lysophospholipids in the extracellular space is unknown. HSA (human serum albumin) is the most abundant carrier protein in blood plasma and plays an important role in determining the absorption, distribution, metabolism and excretion of drugs. In the present study, LPE (lysophosphatidylethanolamine) was used as the ligand to analyse the interaction of lysophospholipids with HSA by fluorescence quenching and crystallography. Fluorescence measurement showed that LPE binds to HSA with a Kd (dissociation constant) of 5.6 microM. The presence of FA (myristate) decreases this binding affinity (Kd of 12.9 microM). Moreover, we determined the crystal structure of HSA in complex with both myristate and LPE and showed that LPE binds at Sudlow site I located in subdomain IIA. LPE occupies two of the three subsites in Sudlow site I, with the LPE acyl chain occupying the hydrophobic bottom of Sudlow site I and the polar head group located at Sudlow site I entrance region pointing to the solvent. This orientation of LPE in HSA suggests that HSA is capable of accommodating other lysophospholipids and phospholipids. The study provides structural information on HSA-lysophospholipid interaction and may facilitate our understanding of the transport and distribution of lysophospholipids.
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PMID:Structural basis of transport of lysophospholipids by human serum albumin. 1960 29

Amino groups in proteins can non-enzymatically react with reducing sugars to generate a structurally diverse group of compounds referred to as advanced glycation end products (AGEs). The in vivo formation of AGEs contributes to some of the complications of diabetes including atherosclerosis, cataract formation, and renal failure. The formation of AGEs is dependent on both sugar and protein concentrations. Increases in temperature, pH, and exposure time of sugars to the proteins also play a significant role in the rate of AGE formation. This study focuses on the use of a combination of analytical techniques to study the in vitro AGE formation of HSA with dihydroxyacetone phosphate (DHAP), a ketose generated during glycolysis, and its dephosphorylated analog, dihydroxy acetone (DHA), commonly used as a browning reagent in skin tanning preparations. The extent of AGE formation was affected by DHAP and DHA concentrations and by the duration of HSA exposure to these glycating agents. Increases in temperature and pH sped the glycation process and enhanced the formation of the AGEs of HSA. MALDI-TOF mass spectroscopic data provided a reliable result to evaluate the extent of the AGE formation.
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PMID:In vitro glycation of human serum albumin by dihydroxyacetone and dihydroxyacetone phosphate. 2219 36


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