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

Clonal attenuation can be defined as the gradual depletion of the replicative potentials of individual clones of mammalian somatic cells. Publications from the author's laboratory and from other laboratories are reviewed that support the proposition that clonal attenuation is a continuous process throughout the life course and that it occurs in vivo in primates. The puzzling discordance between the mass culture results from the laboratories of the late Vincent Cristofalo (tissue from living subjects) and those from the Martin laboratory (tissue predominately from autopsy subjects) is discussed. Finally, the implications of clonal attenuation and replicative senescence, for such major age-related pathologic processes as neoplasia, atherosclerosis, benign prostatic hyperplasia, and osteoarthritis, are addressed; these and other disorders of aging can be characterized as a mixture of atrophy and hyperplasia, presumably related to a failure of homeostatic cell-cell interactions in aging tissues. For the case of neoplasia, an argument can be made that such failures precede what is increasingly regarded as the most critical step in carcinogenesis-the evolution of a mutator phenotype.
 ...
PMID:Clonal attenuation of somatic cells in aging mammals: a review of supportive evidence and its biomedical significance. 1771 99

Peroxisome proliferator-activated receptor gamma (PPAR gamma) are members of the largest nuclear hormone receptor family of transcription factors (1). PPAR gamma (PPARgamma) plays an important role in adipogenesis, control of sensitivity to insulin, inflammation and atherosclerosis but recent studies also suggest that PPARgamma is involved in cell cycle withdrawal. PPARgamma can promote cell differentiation, exert an antiproliferative action and inhibit angiogenesis (2, 3). However, there are studies showing that activation of PPARgamma promotes the development of colon cancer (4). These data are in sharp contrast with studies that attribute anticancer effects to PPARgamma in gastrointestinal malignancies. Probably, the action of PPARgamma on cell cycle and proliferation depends on the cell type and presence of other stimuli that predispose cells to cancer development. Amidated and non-amidated gastrins may play an important role in the proliferation and carcinogenesis of GI cancers. It is known that gastrin peptides activate phosphorylation of Protein Kinase B (PKB/Akt) and anti-apoptotic signalling but there is little known about the link between gastrins and PPARgamma receptors in relation to apoptosis.
 ...
PMID:Transcriptional upregulation of gastrin in response to peroxisome proliferator-activated receptor gamma agonist triggers cell survival pathways. 1819 88

Heme oxygenase-1 (HO-1) is an inducible rate-limiting enzyme which catalyzes group heme into carbon monoxide, iron and bilirubin. In the recent years, HO-1 expression has been reported as an important protective endogenous mechanism against physical, chemical and biological stress. In this regard, induction of this enzyme has shown beneficial effects in several pathologic conditions, such as inflammatory processes, atherosclerosis, carcinogenesis, ischemia-reperfusion systems or degenerative diseases. Complex intracellular signalling cascades mediate the expression of HO-1 in response to external stimuli, Transcription factors, as nuclear factor E2-related factor-2, activator protein-1, and nuclear factor-kappa B, and some of their upstream kinases, mitogen-activated protein kinases, phosphatidylinositol 3-kinase, or protein kinases A, C are responsible of the HO-1 gene expression. The purpose of this article is to review the increasing number of natural and synthetic molecules reported to induce HO-1 as additive mechanism responsible for their therapeutic effects; experimental and pathological conditions as well as possible signalling mechanism involved in HO-1 expression by this compounds are described. Controlled upregulation of this enzyme, or its catalytic activity, has shown antioxidant, anti-proliferative, anti-apoptotic and anti-inflammatory properties. For this reason, pharmacologic modulation of HO-1 system may represent an effective and cooperative strategy to intervene in several pathologic conditions.
 ...
PMID:Inducers of heme oxygenase-1. 1828 74

The peroxisome proliferators-activated receptors gamma (PPAR) belong to the family of nuclear receptors, which directly regulate transcription of target genes. PPARgamma take part in many processes such as adipogenesis, glucose and lipid metabolism, atherosclerosis and inflammation and carcinogenesis. The expression of PPARgamma was detected in normal and tumor cells of endocrine glands. Activation of receptors by specific ligands of PPARgamma induces inhibition of cell proliferation, induction of apoptosis and terminal differentiation as well as inhibition of angiogenesis. In the present paper the structure, tissue expression and biological function of PPARgamma are presented. The reports about oncostatic effects of PPARgamma agonists in pituitary adenomas, thyroid cancers and adrenal tumor are reviewed.
 ...
PMID:[The role of peroxisome proliferators-activated receptors (PPARgamma) in neoplasms of endocrine glands]. 1846 91

Bisacurone, one of the active compounds of the traditionally used indigenous herb Curcuma longa Linne (Zingiberaceae), has anti-oxidant, anti-inflammatory, and anti-metastatic activities. We studied how the level of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules in the development of atherosclerosis as well as carcinogenesis and metastasis, might be affected by bisacurone in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs). Bisacurone dose-dependently inhibited TNF-alpha-mediated expression of VCAM-1. It showed significant suppressive effect on ROS generation in response to TNF-alpha stimulation and it blocked nuclear factor-kappa B (NF-kappaB) p65 translocation into the nucleus and phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also inhibited phosphorylation of Akt and PKC, which are upstream in the regulation of VCAM-1 by TNF-alpha. Furthermore, bisacurone decreased U937 monocyte and human oral cancer cell (Hep-2, QLL-I, SCC-15) adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of these cells by regulating the expression of critical adhesion molecules by TNF-alpha. Thus, bisacurone may be beneficial in the treatment of inflammatory diseases, such as atherosclerosis, where inflammatory monocytes are involved in their pathology, and, moreover, in the development of tumors.
 ...
PMID:Bisacurone inhibits adhesion of inflammatory monocytes or cancer cells to endothelial cells through down-regulation of VCAM-1 expression. 1860 74

The E-cadherin/beta-catenin/T-cell factor (Tcf) signaling pathway plays a crucial role in embryogenesis and carcinogenesis and has recently emerged in atherosclerosis. The aim of this work was to investigate whether this signaling pathway is involved in smooth muscle cell proliferation induced by oxidized low-density lipoprotein (LDL). In human aortic smooth muscle cells, mitogenic concentration of mildly oxidized LDL induced the activation of beta-catenin, as assessed by the dissociation of the beta-catenin/cadherin complex, and the concomitant rise of active beta-catenin in the cytosol. The oxidized LDL-induced rise of active beta-catenin required metalloproteinase activation, as well as epidermal growth factor receptor and Src signaling, as assessed by the use of pharmacological inhibitors and cells overexpressing a SrcK-inactive form. The concomitant phosphatidylinositol 3-kinase/Akt activation and glycogen synthase kinase 3-beta phosphorylation induced the inhibition of the proteasomal degradation of beta-catenin. Then active beta-catenin associated with Tcf4 and translocated into the nucleus. This enhanced the expression of the cell cycle activator cyclin D1. This crucial role of beta-catenin in the mitogenic effect of oxidized LDL was confirmed by silencing beta-catenin by specific small interfering RNA that blocked DNA synthesis. Immunohistochemistry staining of stable and disrupted plaques from carotid endarterectomy sections showed a correlation between active beta-catenin and Ki67, a proliferation marker, and a more intense staining in the smooth muscle cell layer surrounding the lipid core of disrupted plaques. In conclusion, the beta-catenin pathway is required for the mitogenic effect of oxidized LDL on human aortic smooth muscle cells. This study highlights the putative important role of the E-cadherin/beta-catenin/Tcf signaling pathway in atherosclerosis.
 ...
PMID:E-cadherin/beta-catenin/T-cell factor pathway is involved in smooth muscle cell proliferation elicited by oxidized low-density lipoprotein. 1870 80

Reactive oxygen species (ROS) are widely considered to be a causal factor in aging and in a number of pathological conditions, such as atherosclerosis, carcinogenesis and infarction. Their role in bone metabolism is dual, considering their effects under physiological or pathological conditions. Under physiological conditions, the production of ROS by osteoclasts helps accelerate destruction of calcified tissue, thus assisting in bone remodeling. In pathological conditions, when a bone fractures, e.g., radical generation is remarkably high. However, though the increases in osteoclastic activity and ROS production are linked in many skeletal pathologies, it remains to be clarified whether increased ROS production overwhelms antioxidant defenses, leaving the individual open to hyperoxidant stress.
 ...
PMID:Oxidative stress, free radicals and bone remodeling. 1884 68

Increased activity of the renin angiotensin system with enhanced levels of angiotensin II leads to oxidative stress with endothelial dysfunction, hypertension, and atherosclerosis. Epidemiologic studies revealed a higher cancer mortality and an increased kidney cancer incidence in hypertensive patients. Because elevated angiotensin II levels might contribute to carcinogenesis, we tested whether angiotensin II induces DNA damage in the kidney. In isolated perfused mouse kidneys, as little as 1 nmol/L angiotensin II caused a significant increase in DNA strand breaks, measured with the comet assay. This damage was independent of the hemodynamic effect of angiotensin II and mediated by the angiotensin II type 1 receptor. Angiotensin II also caused double-strand breaks in the cells of the isolated perfused kidney, detected with an antibody against the double-strand break marker gamma-H2AX. Studies in cell culture allowed further characterization of the DNA damage induced by angiotensin II. Single- and double-strand breaks, abasic sites, and 7,8-dihydro-8-oxo-guanine, all types of oxidative DNA lesions, were detected in angiotensin II-treated renal cells. The majority of detected strand breaks was repaired within 1 hour, but double-strand breaks increased and persisted for at least 24 hours.
 ...
PMID:Angiotensin II induces DNA damage in the kidney. 1901 Aug 96

Conjugated linoleic acid (CLA) refers to a group of fatty acid isomers of linoleic acid. Recent research shows that CLA affects body composition, lipoprotein metabolism, inflammationand carcinogenesis. Therefore, CLA may have potential as a therapeutic nutrient with respect to many common diseases, including obesity, atherosclerosis, chronic inflammatory diseases and cancer. Animal studies show that CLA is a potent anti-adipogenic nutrient, reducing adipose tissue mass and increasing lean mass. However, the effect of CLA on body composition in human subjects has been less spectacular. Several studies have demonstrated that CLA significantly improves plasma cholesterol and triacylglycerol metabolism in a number of animal models. These studies also showed that CLA inhibits the progression and pathogenesis of atherosclerosis. Whilst CLA has also been shown to improve triacylglycerol metabolism in human subjects, it has not been determined whether CLA affects atherogenesis. Animal models show that CLA-rich diets modulate the inflammatory response and preliminary trials with human subjects show that CLA affects the cell-mediated immune response. The molecular basis of the health effects of CLA has not been elucidated, but it is probable that CLA mediates its effect in a number of ways including altered eicosanoid or cytokine metabolism and/orby a direct effect of dietary fats on gene transcription. Most of our knowledge is based on in vitro and animal studies; the challenge is to define the nature and molecular basis of any health effects of CLA in human subjects.
 ...
PMID:Conjugated linoleic acid: a novel therapeutic nutrient? 1908 21

Tissue damage caused by oxidative stress has been implicated in aging, carcinogenesis, atherosclerosis and neurodegeneration. In xeroderma pigmentosum (XP) and Cockayne syndrome (CS), oxidative stress is associated with promoted occurrence of skin cancers and progressive neurodegeneration, because decreased DNA repair and persistent DNA damage can result in augmented oxidative nucleotide damage. Oxidative nucleotide damage has been investigated mainly in isolated human skin and blood cells or their cell lines, in which CS cells may be more sensitive to oxidative DNA lesions than XP cells. However, cells from patients with XP group A (XPA) show defective repair of 8, 5'-(S)-cyclo-2'-deoxyadenosine, a free radical-induced endogenous DNA lesion and antioxidant system seems to be disturbed variously in cells from XP patients. We have neuropathologically investigated the involvement of oxidative stress in the brains of XPA and CS autopsy cases and clarified the enhanced lipid peroxidation and protein glycation in the pallidal and cerebellar degeneration. Also, oxidative nucleotide damage with reduced expression of superoxide dismutases has been identified in the basal ganglia lesions, lending further weight involvement of oxidative stress in neurodegeneration in XPA patients. Additionally, we are developing ELISA analysis of oxidative stress markers in the urine and cerebrospinal fluid from XP patients, which will aid with further data on oxidative stress in pathogenesis of XP.
 ...
PMID:Roles of oxidative stress in xeroderma pigmentosum. 1918 Nov 17


<< Previous 1 2 3 4 5 6 7 8 9 10