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)

The development and progression of coronary atherosclerosis is influenced by a variety of genetic and environmental factors. Among the genetic factors, the cell surface receptor LRP/A2MR (LDL receptor-related protein/alpha2-macroglobulin receptor) was shown to be involved in a variety of biological processes leading to atherosclerotic plaque formation. That is why the individual expression of this receptor may, therefore, be considered as an evident predictor for coronary atherosclerosis. In this clinical ex vivo study the expression was measured by competitive RT-PCR and macroarray analysis in native monocytes. Both methods were first tested in an in vitro model using different human cells and cell lines (fibroblasts: chorion, skin; endothelial cells from umbilical cord vein; monocyte cell line: Mono-Mac-6): after stimulation with an LRP/A2MR ligand, leptin, the anticipated direct effect of this ligand, namely an increase in both receptor mRNA and protein expression, was confirmed. In disease-related ex vivo studies the mRNA and protein-expression of LRP/A2MR was investigated in 36 male patients suffering from myocardial infarction. In comparison to the control group (36 healthy male blood donors), a significant up-regulation of mRNA was detected in the myocardial infarction patient group (control: 122.3 ag/cell versus patients: 223 ag/cell; P<0.001). Investigating the LRP/A2MR protein expression a significant down-regulation of protein expression was determined in the patient group (control: 6 pg/cell versus patients: 1.6 pg/cell; P<0.001). The ratio of LRP/A2MR mRNA and protein expression is obviously an evident marker for coronary atherosclerosis, recommendable for the assessment of the individual coronary risk profile.
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PMID:Role of LDL receptor-related protein (LRP) in coronary atherosclerosis. 1465 44

LDL receptor-related protein/alpha2-macroglobulin receptor (LRP1/A2MR) a multiligand receptor is considered as not only being a possible risk factor of neurodegenerative diseases like Alzheimer's disease but also as determining the progression of other complex diseases like atherosclerosis and cancer. Although a large number of in vitro studies have highlighted its functional importance, as yet not enough is known about the clinical importance of the genetic background of LRP1 in human diseases. The aim of this ex vivo/in vivo study of 448 subjects was to present data on genetic LRP1 variants of healthy European Caucasians from Central Germany. Genotype-dependent LRP1 expression was analyzed in a representative subgroup (gene expression: n = 127, protein expression: n = 44). These data were evaluated in comparison to other published clinical LRP1 studies. For 15 functionally interesting genetic variants the genotype and allele distributions of the German Caucasians were presented in relation to their in vivo LRP1 gene and protein expression. A direct influence of the LRP1 promoter polymorphism c.1-25C>G on the human in vivo LRP1 expression level was demonstrated. In an analysis of 48 further studies genomic and functional results were evaluated. The analysis especially on Alzheimers's disease partly highlighted contradictory results, but suggested that ethnic as well as genomic characteristics determine LRP1 expression and must be considered in clinical investigations on human LRP1.
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PMID:Genetic and functional characteristics of the human in vivo LRP1/A2MR receptor suggested as a risk marker for Alzheimer's disease and other complex (degenerative) diseases. 1528 2

The role of sialic acid (SA) in the pathogenesis of atherosclerosis and as a predictor of cardiovascular events has attracted much attention in recent years. However, most studies investigating the role of total and lipid-bound sialic acids (TSA and LSA) in the pathogenesis of atherosclerosis lack information on the reason for the elevated SA concentrations in coronary heart disease and myocardial infarction. Since the inflammation-sensitive proteins are glycoproteins with SA residues, an increase in their levels due to some type of acute-phase reaction or inflammation could be responsible for the elevated TSA levels in acute myocardial infarction (AMI). Elevated serum SA levels might also be due to either shedding or secretion of free SA from the cell or cell membrane surface if neuraminidase levels are increased, or to the release of cellular SA-containing glycolipids and/or glycoproteins into plasma from myocardial cells after AMI. The aim of the present study was to investigate both the possible role of SA-rich inflammation-sensitive proteins and the cell damage due to elevated serum TSA levels in AMI. A possible role of serum LSA as an indicator of the shedding or secretion of SA from the cell or cell membrane surface in AMI was also evaluated. The study included 38 subjects with AMI and 32 healthy volunteers. Serum TSA and LSA were determined using the methods of Warren and Katopodis, respectively. The concentrations of serum SA-rich inflammation-sensitive proteins, namely alpha1-antitrypsin, alpha2-macroglobulin and ceruloplasmin were determined immunoturbidimetrically. Our data showed that: a) mean levels of serum TSA and LSA and SA-rich inflammation-sensitive proteins in patients with AMI were significantly increased; and b) there was a significant positive correlation between TSA and LSA and alpha1-antitrypsin in patients with AMI. Since the transfer of free SA to lipoproteins is required for an increase in serum LSA levels, and free SA for this transfer can be provided by the secretion of SA from the cell, it is obvious that the shedding or secretion of SA from the cell membrane surface or release of cellular SA from cells into the bloodstream due to cell damage after AMI also occur after AMI. As a result, we can report that either the shedding or secretion of SA from the cell or cell membrane surface and the increased output of SA-rich inflammation-sensitive proteins may together be responsible for the elevated TSA levels in AMI.
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PMID:Relationship between serum sialic acids, sialic acid-rich inflammation-sensitive proteins and cell damage in patients with acute myocardial infarction. 1647 8

Adiponectin is a fat cell-secreted hormone with antidiabetic and anti-inflammatory activities. The reduced adiponectin levels are associated with obesity-related metabolic syndrome. Replenishment of this hormone into animal models can improve insulin sensitivity, decrease blood glucose and lipid levels, and prevent the development of atherosclerosis and fatty liver injury. Despite these findings, the underlying molecular mechanisms remain largely unknown. Here, we have used affinity chromatography to purify the protein complexes that are associated with adiponectin in human serum. The nature of these adiponectin-binding proteins was analyzed by MS/MS. Eight proteins from the adiponectin-containing protein mixtures have been identified. Many of them, including thrombospondin-1 (TSP-1), histidine-rich glycoprotein, kininogen 1, and alpha 2 macroglobulin (alpha2M), are well-known glycoproteins involved in the regulation of inflammation, angiogenesis, and tissue remodeling. Coimmunoprecipitation and radioligand competitive-binding assays confirmed the direct interactions between adiponectin and alpha2M, or TSP-1. Moreover, these specific bindings were also detected in the serum samples derived from both healthy human subjects and patients with type 2 diabetes. In summary, our study demonstrated that, in the circulation, adiponectin forms protein complexes with other serum proteins. These proteins might serve as the physiological-binding partners of adiponectin and regulate its bioavailability and biological activities.
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PMID:Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin. 1676 90

Psoriasis is a chronic, relapsing, inflammatory - proliferative disease, belonging to the group of autoimmune disorders. Although the disease process concerns mainly the skin, this is a systemic inflammation. In psoriasis there is an increased synthesis of proinflammatory proteins, such as: C-reactive protein (CRP), interleukin 1 (IL-1), IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), alpha2-macroglobulin, alpha1-antitrypsin and ceruloplasmin. Many studies have shown increased incidence of the metabolic syndrome in patients with psoriasis. There is also relationship between severity of psoriasis and severity of the various components of metabolic syndrome (impaired glucose tolerance or diabetes, abdominal obesity, atherogenic dyslipidemia and hypertension). Chronic inflammation seems to be a link between psoriasis and various components of metabolic syndrome. Proinflammatory cytokines may cause atherosclerosis, insulin resistance, hypertension and type 2 diabetes. Presence of obesity and particular components of the metabolic syndrome may also play an important role in the pathogenesis of chronic kidney disease in patients with psoriasis. The primary intervention in patients with psoriasis and metabolic syndrome in order to reduce cardiovascular risk are lifestyle modifications, i.e. increased physical activity and dietary treatment of obesity, in combination with pharmacotherapy of particular components of metabolic syndrome.
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PMID:[Metabolic disorders in patients with psoriasis]. 2251 79

Here, we provide a comprehensive review of current findings concerning the biochemistry and physiological functions of ADAMTS7, a metalloprotease that is known to interact with cartilage oligomeric matrix protein, progranulin, and alpha2-macroglobulin. Such broad substrate specificity and potentially diverse physiological functions make ADAMTS7 an interesting enzyme to study. ADAMTS7 has been shown to play a role in the pathogenesis of arthritis and disc disorders. More recently, the ADAMTS7 locus is identified to have a strong association with coronary atherosclerotic disease. However, the role of ADAMTS7 in the development of atherosclerosis is yet to be determined. The development of an easy and high throughput assay for ADAMTS7 activity and appropriate animal models will allow us to uncover the novel mechanisms of coronary arterial disease.
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PMID:Biochemistry and physiological functions of ADAMTS7 metalloprotease. 2422 22


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