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)

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear transcription factors that belong to the steroid receptor superfamily. This family of PPARs includes PPARalpha, PPARdelta, PPARgamma1, and PPARgamma2. These PPARs are related to the T3 and vitamin D(3) receptors and bind to a hexameric direct repeat as a heterodimeric complex with retinoid receptor Xalpha. PPARs regulate the expression of a wide array of genes that encode proteins involved in lipid metabolism, energy balance, eicosanoid signaling, cell differentiation, and tumorigenesis. A unique feature of these steroid-like receptors is that the physiologic ligands for PPARs appear to be fatty acids from the n-6 and n-3 families of fatty acids and their respective eicosanoid products. This review describes the characteristics, regulation, and gene targets for PPARs and relates their effects on gene expression to physiologic outcomes that affect lipid and glucose metabolism, thermogenesis, atherosclerosis, and cell differentiation.
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PMID:Peroxisome proliferator-activated receptors: a family of lipid-activated transcription factors. 1050 27

Several decades after the discovery of selenium as an essential trace element in vertebrates approximately 20 eukaryotic and more than 15 prokaryotic selenoproteins containing the 21st proteinogenic amino acid, selenocysteine, have been identified, partially characterized or cloned from several species. Many of these proteins are involved in redox reactions with selenocysteine acting as an essential component of the catalytic cycle. Enzyme activities have been assigned to the glutathione peroxidase family, to the thioredoxin reductases, which were recently identified as selenoproteins, to the iodothyronine deiodinases, which metabolize thyroid hormones, and to the selenophosphate synthetase 2, which is involved in selenoprotein biosynthesis. Prokaryotic selenoproteins catalyze redox reactions and formation of selenoethers in (stress-induced) metabolism and energy production of E. coli, of the clostridial cluster XI and of other prokaryotes. Apart from the specific and complex biosynthesis of selenocysteine, selenium also reversibly binds to proteins, is incorporated into selenomethionine in bacteria, yeast and higher plants, or posttranslationally modifies a catalytically essential cysteine residue of CO dehydrogenase. Expression of individual eukaryotic selenoproteins exhibits high tissue specificity, depends on selenium availability, in some cases is regulated by hormones, and if impaired contributes to several pathological conditions. Disturbance of selenoprotein expression or function is associated with deficiency syndromes (Keshan and Kashin-Beck disease), might contribute to tumorigenesis and atherosclerosis, is altered in several bacterial and viral infections, and leads to infertility in male rodents.
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PMID:Selenium in biology: facts and medical perspectives. 1107 17

Peroxisome proliferator-activated receptors are nuclear receptors that were isolated for their ability to modulate lipid metabolism. Similar to other members of the nuclear receptor family, peroxisome proliferator-activated receptors bind ligand as heterodimers and exert their effects via transcriptional regulation through their DNA binding domains. During the past decade, it has become clear that peroxisome proliferator-activated receptors also contribute to a variety of different biologic processes, including atherosclerosis, insulin resistance, and more recently, cancer. In this review, we discuss the evidence for the different peroxisome proliferator-activated receptors' roles in tumorigenesis and also their potential application for the treatment and prevention of neoplastic diseases.
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PMID:Peroxisome proliferator-activated receptors: roles in tumorigenesis and chemoprevention in human cancer. 1114 91

Elderly humans have altered cellular redox levels and dysregulated immune responses, both of which are key events underlying the progression of chronic degenerative diseases of ageing, such as atherosclerosis and Alzeimer's disease. Poorly maintained cellular redox levels lead to elevated activation of nuclear transcription factors such as NFkB and AP-1. These factors are co-ordinately responsible for a huge range of extracellular signalling molecules responsible for inflammation, tissue remodelling, oncogenesis and apoptosis, progessess that orchestrate many of the degenerative processess associated with ageing. It is now clear that levels of endogenous anti-oxidants such as GSH decrease with age. This study aimed to investigate the potential of exogenous anti-oxidants to influence inflammatory responses and the ageing process itself. We investigated the potential of the dietary antioxidant, quercetin, to reverse the age related influences of GSH depletion and oxidative stress using in vitro human umbilical vein endothelial cells (HUVEC) and human skin fibroblast (HSF) cell models. Oxidative stress-induced inflammatory responses were investigated in a GSH depletion and a Phorbol 12-myristate 13-acetate (PMA)-induced stress model. As measured with a sensitive HPLC fluorescence method, GSH in HUVEC was depleted by the addition of L-buthionine-[S,R]-sulfoxiniine (BSO), a gamma-glutamylcysteine synthetase inhibitor, to the culture medium at a concentration of 0.25 mM. Time course studies revealed that the GSH half-life was 4.6 h in HUVEC. GSH depletion by BSO for 24 h led to a slight increase in intracellular adhesion molecule - 1 (ICAM1) expression and prostaglandin E2 (PGE2) secretion in both types of cells. However, GSH depletion markedly enhanced PMA-induced ICAM and PGE2 production in HUVEC. Responses were progressively elevated following prolonged BSO treatment. Inhibition studies showed that 1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H7), a protein kinase C (PKC) inhibitor, not only abolished most of PMA-induced ICAM-1 expression and PGE2, production, but also eliminated GSH depletion-enhanced PMA stimulation. This enhancement was also inhibited by supplementation with quercetin. The results clearly demonstrate that GSH depletion increased the susceptibility of vascular endothelial cells and fibroblasts to oxidative stress associated inflammatory stimuli. This increased in vitro susceptibility may be extrapolated to the in vivo situation of ageing, providing a useful model to study the influence of micronutrients on the ageing process. In conclusion, these data suggest that dietary antioxidants could play a significant role in the reduction of inflammatory responses.
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PMID:Antioxidants may contribute in the fight against ageing: an in vitro model. 1116 75

Apoptosis is a cell suicide program characterized by distinct morphological (cell shrinkage, membrane blebbing, pyknosis, chromatin margination, denser cytoplasmic images) and biochemical (e.g., DNA fragmentation into distinct ladders; degradation of apoptotic markers such as PARP and nuclear lamins) features. It is involved in multiple physiological processes examplified by involution of mammary tissues, embryonic development, homeostatic maintenance of tissues and organs, and maturation of the immune system, as well as in many pathological conditions represented by neurologic degeneration (Alzeimer's disease), autoimmune and inflammatory diseases, etiology of atherosclerosis, AIDS, and oncogenesis and tumor progression. Numerous molecular entities have been shown to regulate the apoptotic process. This review provides a concise summary of the recent data on the role of oncogenes/tumor suppressor genes, cytokines and growth factors/growth factor receptors, intracellular signal transducers, cell cycle regulators, reactive oxygen species or other free radicals, extracellular matrix regulators/cell adhesion molecules, and specific endonucleases and cytoplasmic proteases (the ICE family proteins) in regulating cell survival and apoptosis. Elucidation of the molecular mechanisms regulating apoptosis bears tremendous impact on enhancing our understanding of many diseases inflicting the human beings and undoubtedly brings us hope for the cure of these diseases.
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PMID:Apoptosis: A Current Molecular Analysis. 1117 95

We have investigated 28 atherosclerotic plaques of human carotid arteries with a panel of 39 microsatellite markers for the presence of LOH. The objective of this research was to verify if LOH, described in association with tumorigenic process, could be involved also in benign fibroproliferative disease. Seventy percent of samples demonstrated allelic imbalance: 50% of cases showed LOH at a minimum of one locus, 3.5% at a minimum of two loci and 14.3% at three or more loci. The percentages of LOH ranged between 3.8 and 14.3% and the highest involved polymorphic marker is the NOS3 internal dinucleotide repeat. Our results indicate that, like tumorigenesis, the atherogenic process could also involve LOH mechanism. Furthermore, the finding regarding the NOS3 internal polymorphism suggests a possible role of the gene as cofactor in formation of the atheromas.
Atherosclerosis 2001 Dec
PMID:Loss of heterozygosity of the NOS3 dinucleotide repeat marker in atherosclerotic plaques of human carotid arteries. 1173 Aug 5

The elucidation of the potential health benefits of tea beverage continues to be a focus of research in many laboratories. Beneficial effects of tea have been particularly evident in animal tumorigenesis models, with green and black tea frequently demonstrating similar effectivity. Human data are now emerging to support a beneficial role for tea in cardiovascular disease, but the data with respect to cancer risk at various sites remain inconclusive. The constituent flavonoids of green and black tea beverage are known to be potent antioxidants, and although this may be a major factor in explaining their biological activity, it appears that the gallated flavonoids in particular (e.g., epigallocatechin gallate and the gallated theaflavins) impact on a wide range of molecular targets that influence cell growth and more specifically pathways such as those involving angiogenesis. Data on the pharmacokinetic properties of tea flavonoids, primarily on the catechins and therefore related most closely to green tea, have provided indications of the plasma levels and circulating molecular forms that may be expected in humans following tea consumption. The structural complexity of black tea flavonoids, in particular the thearubigins, has hindered efforts to describe their bioavailability and to perform mechanistic studies. Recent studies on the effects of catechins and theaflavins on growth factor-, nuclear factor-kappaB-, and stress-mediated signal transductions are described in this review, where possible in relation to their bioavailability in vivo. These studies indicate that effects that may be relevant to both cancer and atherosclerosis are often observed at tea flavonoid levels that could realistically be encountered in vivo. However, more studies need to be performed using those molecular forms of tea flavonoids (methylated, sulfated, and glucuronidated conjugates) that are the major circulating species encountered following tea consumption. Such studies, combined with further human epidemiological and interventional data, should ultimately elucidate the full beneficial potential of tea beverage on human health.
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PMID:Tea flavonoids: bioavailability in vivo and effects on cell signaling pathways in vitro. 1181 77

Peroxisome proliferator-activated receptors control many cellular and metabolic processes. They are transcription factors belonging to the family of ligand-inducible nuclear receptors. Three isotypes called PPARalpha, PPARbeta/delta and PPARgamma have been identified in lower vertebrates and mammals. They display differential tissue distribution and each of the three isotypes fulfills specific functions. PPARalpha and PPARgamma control energy homoeostasis and inflammatory responses. Their activity can be modulated by drugs such as the hypolipidaemic fibrates and the insulin sensitising thiazolidinediones (pioglitazone and rosiglitazone). Thus, these receptors are involved in the control of chronic diseases such as diabetes, obesity, and atherosclerosis. Little is known about the main function of PPARbeta, but it has been implicated in embryo implantation, tumorigenesis in the colon, reverse cholesterol transport, and recently in skin wound healing. Here, we present recent developments in the PPAR field with particular emphasis on both the function of PPARs in lipid metabolism and energy homoeostasis (PPARalpha and PPARgamma), and their role in epidermal maturation and skin wound repair (PPARalpha and PPARbeta).
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PMID:Peroxisome proliferator-activated receptors (PPARs): from metabolic control to epidermal wound healing. 1197 Dec 2

Platelet-derived growth factor (PDGF) plays a critical role in regulating the development and functional control of various tissues and has been implicated in the pathogenesis of serious diseases, including cancer and atherosclerosis. Given the emerging role of PDGF in the development and function of male gonads, we compared the expression profiles of the mRNAs of the PDGF A- and B-chains and of the PDGF receptor (PDGFR) alpha- and beta-subunits in fetal and adult human testis. The immunohistochemical localization of the corresponding proteins in fetal, adult, and diseased human testicular tissues was also analyzed. PDGFs and PDGFRs mRNAs were readily detected by both Northern analysis and RT-PCR. The transcript levels were higher during 16-20 wk gestation, significantly lower at 24-28 wk, and increased in the adult. An identical pattern of protein expression was confirmed by immunohistochemistry, although the cellular localization of the PDGF system changes during postnatal development, concomitantly with the progression of spermatogenesis. In the testicular samples from patients affected by either complete aplasia of germ cells or various grades of spermatogenic arrest, the immunohistochemical localization of PDGFs and PDGFRs was different from normal, confirming a close connection between germ cells and PDGF system distribution. These results indicate that PDGF, through complex interactions, could play a leading role in ontogenesis and testicular pathophysiology in humans. Finally, the expression of PDGF ligands and receptor proteins in Leydig cell tumors suggests a relationship of the PDGF system to tumorigenesis or tumor progression in this testicular neoplasm.
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PMID:Expression of platelet-derived growth factor-A (PDGF-A), PDGF-B, and PDGF receptor-alpha and -beta during human testicular development and disease. 1199 82

The occurrence of infections in organ transplantation is one of the most significant determinants of transplant outcome, because it is the most common life-threatening complication of long-term immunosuppressive therapy. Recently, besides the well-known direct effect of infections, other relevant biochemical factors such as cytokines, chemokines and growth factors have been considered. Aim of this review is to deal with the infections by mainly considering the unusual consequences of several infectious diseases like malignancies, graft loss and atherosclerosis. The number of patients affected by malignancies is increasing in all registries. Viral pathogens play a pathophysiological role in the development of the most frequent malignancies after solid organ transplantation. In some cases viruses act by altering cell transformation. Moreover, some pathogens may contribute to global immunosuppression and work together to promote oncogenesis. The viral load surveillance is recommended in the prevention of malignancies. The BK virus nephropathy in renal transplant recipients is emerging as an unusual consequence of graft loss. In this paper we examine the risk factors, the clinical characteristics and especially the diagnostic tools and treatments actually available. The third unusual consequence is the transplant vascular sclerosis, a multifactorial late complication of solid organ transplantation. The transplant vascular sclerosis has emerged as an important limitation in long-term graft survival. Several epidemiological, clinical and therapeutic interventional studies have shown how several potential contributing etiologic factors, such as Chlamydia and CMV infection, have been identified as being definitely associated with the development of transplant vascular sclerosis.
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PMID:[Unusual infections in transplantation]. 1243 46


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