Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0004153 (atherosclerosis)
77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitronectin is one of the major extracellular matrix proteins that accumulates in atherosclerotic lesions. A monoclonal antibody (EMR1a/212D) specifically stained the extracellular regions in thickened intima which colocalized well with lipid deposition. The antigenic glycoprotein with a molecular weight of 66KDa was revealed to be rabbit vitronectin. When homogenates of WHHL rabbit atheroma were subjected to immunoblot analysis using EMR1a/212D, four molecules with molecular weight 66, 56, 50 and 47KDa were detected. To confirm whether these smaller immunopositive bands were derived from mature vitronectin, another monoclonal antibody (EMR1b/244H) recognizing the polypeptide region of vitronectin was prepared. All four molecules were detected by EMR1b/244H as well as by EMR1a/212D. Two smaller vitronectins (56KDa and 50KDa) were found in atherosclerotic lesions and increased markedly during the development of atherosclerosis. On the other hand, the vitronectin detected in normal rabbit aorta was mainly of the mature type, while 56KDa and 47KDa forms were not detected. The total amount of the four vitronectins in atherosclerotic lesions was 38.5 +/- 5.0 ng/mg wet weight tissue, a value approximately 9.5 fold higher than that found in normal aorta. In conclusions, we found massive accumulation of these vitronectins concomitant with atherosclerotic development in rabbit aorta.
...
PMID:Characterization of vitronectins in atherosclerotic lesions. 922 36

Current data suggest that nitric oxide (NO) is a double-edged sword that could result in relaxation and/or cytotoxicity of vascular smooth muscle cells (SMCs) via cGMP- dependent or -independent signal pathways. Stress or heat shock proteins (hsps) have been shown to be augmented in arterial SMCs during acute hypertension and atherosclerosis, both conditions that are believed to correlate with disturbed NO production. In the present study, we demonstrate that NO generated from sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine, and spermine/nitric oxide complex leads to hsp70 induction in cultured SMCs. Western blot analysis demonstrated that hsp70 protein expression peaked between 6 and 12 h after treatment with SNP, and elevated protein levels were preceded by induction of hsp70 mRNA within 3 h. Induction of hsp70 mRNA was associated with the activation of heat shock transcription factor 1 (HSF1), suggesting that the response was regulated at the transcriptional level. HSF1 activation was completely blocked by hemoglobin, dithiothreitol, and cycloheximide, suggesting that the protein damage and nascent polypeptide formation induced by NO may initiate this activation. Furthermore, SMCs pretreated with heat shock (42 degrees C) for 30 min were significantly protected from death induced by NO. Thus, we provide evidence that NO induces hsp70 expression in SMCs via HSF1 activation. Induction of hsp70 could be important in protecting SMCs from injury resulting from NO stimulation.
...
PMID:Nitric oxide induces heat-shock protein 70 expression in vascular smooth muscle cells via activation of heat shock factor 1. 927 25

The vasoactive hormone angiotensin II (Ang II) can stimulate vascular smooth muscle cell (SMC) hypertrophy and proliferation; thus, it may have an important role in the pathogenesis of hypertension, atherosclerosis and restenosis. Several studies have indicated that Ang II bioactivity on SMC may depend, at least in part, on its ability to induce the expression of polypeptide growth factors that can function in an autocrine manner. Here we report that Ang II treatment of rat aortic SMC increases fibroblast growth factor-2 (FGF-2) but not FGF-1 mRNA levels. Increased FGF-2 mRNA expression is first detectable at 30 min after Ang II addition and maximal levels are present at 8 hr. Ang II induction of FGF-2 mRNA levels is dependent on de novo RNA and protein synthesis. The Ang II effect can be blocked by treatment with either the Ang II type 1 receptor-selective antagonist CI-996 or the tyrosine kinase inhibitor genistein. The potent vasoconstrictor and SMC mitogen endothelin-1 can also induce FGF-2 mRNA levels in rat aortic SMC. These results indicate that FGF-2 gene expression is up-regulated by two distinct vasoactive peptides implicated in vascular SMC growth control in vivo.
...
PMID:Angiotensin II and endothelin-1 increase fibroblast growth factor-2 mRNA expression in vascular smooth muscle cells. 943 36

Vascular smooth muscle cells (SMCs), the major cellular constituent of an artery, synthesize the bulk of fibrillar collagens, including type V/XI, which regulates heterotypic collagen fibril assembly. Basic fibroblast growth factor (bFGF) is a heparin-binding polypeptide growth factor that has been implicated in important events during the development of atherosclerosis, such as early intimal SMC proliferation. Here we have investigated the effects of bFGF on aortic SMC expression of type V/XI collagen. Treatment of exponentially growing or serum-deprived subconfluent cultures of bovine aortic SMCs with bFGF decreased the steady-state levels of the mRNAs for collagen type V/XI, including alpha 1(V), alpha 2(V), and alpha 1(XI). The effect of bFGF was time dependent with a two- and a fourfold decrease in alpha 2(V) mRNA observed after treatment for 24 and 48 h, respectively. This decrease resulted from a drop in the rate of alpha 2(V) gene transcription; no change was observed in the stability of the alpha 2(V) mRNA. Furthermore, accumulation of collagen protein decreased upon bFGF treatment. As expected, treatment with bFGF increased the rate of proliferation of serum-deprived SMCs, as judged by DNA content in the cultures, thymidine incorporation, and steady-state mRNA levels of the S-phase-expressed histone H3.2. These results suggest that bFGF plays an important role in the regulation of collagen fibril structure, with potential implications for the development and organization of an atherosclerotic lesion.
...
PMID:Basic fibroblast growth factor decreases type V/XI collagen expression in cultured bovine aortic smooth muscle cells. 944 80

1. Extracellular adenosine triphosphate (ATP) is mitogenic for vascular smooth muscle cells (VSMC) and stimulates several events that are important for cell proliferation: DNA synthesis, protein synthesis, increase of cell number, immediate early genes, cell-cycle progression, and tyrosine phosphorylation. 2. Receptor characterization indicates mitogenic effects of both P2U and P2Y receptors. The P2X receptor is lost in cultured VSMC and is not involved. Several related biological substances such as UTP, ITP, GTP, AP4A, ADP, and UDP are also mitogenic. 3. Signal transduction is mediated via Gq-proteins, phospholipase C beta, phospholipase D, diacyl glycerol, protein kinase C alpha, delta, Raf-1, MEK, and MAPK. 4. ATP acts synergistically with polypeptide growth factors (PDGF, bFGF, IGF-1, EGF, insulin) and growth factors acting via G-protein-coupled receptors (noradrenaline, neuropeptide Y, 5-hydroxytryptamine, angiotensin II, endothelin-1). 5. The mitogenic effects have been demonstrated in rat, porcine, and bovine VSMC and cells from human coronary arteries, aorta, and subcutaneous arteries and veins. 6. The trophic effects on VSMC and the abundant sources for extracellular ATP in the vessel wall make a pathophysiological role probable in the development of atherosclerosis, neointima-formation after angioplasty, and possibly hypertension.
...
PMID:Extracellular ATP: a growth factor for vascular smooth muscle cells. 959 70

Hepatic expression of apolipoprotein (apo) B mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1) has been proposed as a gene therapy approach for lowering plasma low density lipoprotein (LDL) levels. However, high-level expression of APOBEC-1 in transgenic mouse and rabbit livers causes liver dysplasia and hepatocellular carcinoma. To determine the physiological and pathological effects of low-level hepatic expression of APOBEC-1, we used a 52-kb rat APOBEC-1 genomic clone (RE4) to generate transgenic mice expressing low levels of APOBEC-1 (2 to 5 times those in nontransgenic mice). Liver function, liver histology, editing of apoB mRNA at the normal editing site (C6666), and abnormal editing at multiple sites (hyperediting) in these mice were compared with those in transgenic mice expressing intermediate (I-20) or high (I-28) levels of APOBEC-1 in the liver. Hyperediting of mRNA coding for the novel APOBEC-1 target 1 (NAT1) was also examined. In the high-expressing I-28 line, 50% of the mice had palpable tumors at 15 weeks of age, whereas in the intermediate-expressing I-20 line, 50% of the mice had evidence of liver tumors after 1 year. In contrast, low-expressing RE4 mice had normal liver function and histology and did not develop liver tumors when examined at 3 to 17 months of age. Moreover, hyperediting of apoB and NAT1 mRNA in the liver was robust in the I-20 mice but barely detectable in the RE4 mice. The low-level expression resulted in sufficient APOBEC-1 to edit essentially all apoB mRNA at the normal editing site, virtually eliminating apoB-100 and LDL in the plasma of RE4 mice. When RE4 mice were crossed with human apoB transgenic mice, which possess high plasma LDL concentrations, plasma LDL levels in the offspring were reduced to very low levels. These results indicates that long-term hepatic expression of APOBEC-1 at low levels sufficient to eliminate LDL does not cause apparent liver damage or liver tumors in transgenic mice. RE4 APOBEC-1 transgenic mice should prove valuable for studying the roles of apoB-containing lipoproteins in lipid metabolism and atherosclerosis.
...
PMID:Low expression of the apolipoprotein B mRNA-editing transgene in mice reduces LDL levels but does not cause liver dysplasia or tumors. 963 45

The kidney is responsible for regulation of water and electrolyte balance, filtration and absorption of plasma proteins, and control of blood volume and pressure. Homeostasis achieved by the kidney is controlled in large part by the action of hormones or proteins on specific transmembrane receptors. Conversely, many renal diseases, including that resulting from atherosclerosis, are characterised by scarring and abnormal proliferation of cellular components of the kidney, and these processes are mediated in large part by these same receptors. The G protein-coupled receptors constitute a large and diverse class of proteins, characterised by the possession of seven transmembrane-spanning domains. These receptors bind polypeptide growth factors, which function to transmit a variety of signals from the extracellular to the intracellular milieu. The receptor-associated G proteins utilised by the kidney derive their specificity not only by activating or inhibiting various second-messenger molecules, but also by their location on particular cell types. In this review, several G protein-coupled receptors will be discussed from the perspective of their importance to kidney function and to the pathogenesis of renal disease, atherosclerosis, and hypertension.
...
PMID:G protein-coupled receptor signalling in the kidney. 969 74

Atherosclerotic plaques develop in the arterial wall from complex multicellular processes following the early recruitment of circulating monocytes. Infiltration of monocytes is mediated by cell adhesion molecules (CAMs), including vascular cell adhesion molecule-1 (VCAM-1) which is rapidly induced in endothelial cells in response to cytokines. Apolipoprotein E (apo E), a 34-kDa polypeptide, helps protect against atherosclerosis, in part, because apo E phospholipid particles secreted by macrophages may have local protective effects within lesions. Here we have investigated whether purified plasma apo E, complexed with dimyristoyl phosphatidylcholine (DMPC) vesicles, can inhibit cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical vein endothelial cells (HUVECs). Expression of VCAM-1 in endothelial cells after exposure to tumour necrosis factor-alpha (TNF-alpha) or interleukin 1beta (IL-1beta) was quantified by ELISA and shown to be partially inhibited by 17beta-estradiol (40-60% inhibition) or by S-nitroso-L-glutathione, a nitric oxide donor (20-25%). However, preincubations with physiological concentrations (10-100 microg protein/ml) of apo E DMPC did not downregulate VCAM-1 expression, even with extended preincubation times. These findings were confirmed using a fluorescence-activated cell sorter (FACS) for analysis which indicated additionally that apo E-DMPC had no effect on sub-populations within the HUVEC cultures. Finally, apo E-DMPC vesicles were also unable to suppress TNF-alpha-induced upregulation of E-selectin or intercellular adhesion molecule-1 (ICAM-1). We conclude that plasma apo E is unlikely to be important in limiting endothelial activation.
Atherosclerosis 1998 Jul
PMID:Apolipoprotein E and regulation of cytokine-induced cell adhesion molecule expression in endothelial cells. 969 92

Proliferation and directed migration of vascular cells are key components in vascular diseases such as atherosclerosis and restenosis following percutaneous transluminal coronary angioplasty. However, the precise cellular and molecular mechanisms involved in the control of vascular cell proliferation or migration at the tissue level remain largely undefined. Molecules contributing to these processes are elaborated by distinct cell types and act in both autocrine and paracrine modes. They include two broad classes, polypeptide growth factors and vasoactive G-protein-coupled receptor (GPCR) agonists. Examples of the former, such as platelet-derived growth factor, bind to and activate cell surface receptor tyrosine kinases, initiating intracellular biochemical signaling pathways associated with cell proliferation or migration. In contrast, recent evidence suggests that vasoactive GPCR agonists (e.g. angiotensin II, endothelin-1, alpha-thrombin) elicit cell growth indirectly by inducing the production of autocrine or paracrine factors in vascular cells. Recent studies have identified activin A as a novel component of conditioned medium obtained from GPCR agonist-stimulated vascular smooth muscle cells (SMCs). Although activin A alone only weakly stimulated rat aortic SMC DNA synthesis, it demonstrated a potent co-mitogenic effect in combination with either epidermal growth factor (EGF) or heparin binding EGF-like growth factor in these cells, increasing DNA synthesis by up to 5- and 4-fold respectively. Furthermore, in a rat carotid-injury model, activin A mRNA was upregulated within 6 h after injury, followed by increases in immunoreactive protein detected in the expanding neointima 7 to 14 days later. Taken together, these results indicate that activin A is a common vascular SMC-derived growth factor induced by vasoactive agonists that may, either alone or in combination with other factors, contribute to fibroproliferative vascular diseases.
...
PMID:Novel cardiovascular actions of the activins. 1032 Aug 14

Insulin-like growth factor I (IGF-I) is a ubiquitous endocrine, paracrine and autocrine polypeptide, which influences cell proliferation and differentiation in many tissues. Classically, IGF-I has been tied to growth hormone (GH) and has often been considered a surrogate marker of overall GH status. The advent of recombinant technology has made possible studies of GH and IGF-I for the treatment of chronic diseases (such as diabetes mellitus, osteoporosis and muscle atrophy) as well as to forestall the aging process. Examples of currently active areas of research include efforts to define the involvement of IGF-I physiology in bone remodeling, atherosclerosis and neoplasia. Recent epidemiological evidence suggests that individuals with IGF-I levels in the 'high normal' range have increased risk of common cancers relative to individuals with levels in the 'low normal' range. These findings have focused renewed attention on the genetic and non-genetic determinants of serum IGF-I levels. It is unlikely that the serum IGF-I level itself is related directly to risk of neoplasia, but it may serve as a surrogate for a variable that is important in epithelial cell carcinogenesis, such as rate of epithelial cell proliferation. We review relatively new data suggesting that adult serum IGF-I levels are under the control of heritable factors apart from GH. Such factors may influence tissue expression of IGF-I as well as serum IGF-I levels, and influence a number of clinically important outcomes, including bone density and risk of neoplasia. The concept that there is little physiological importance in the heterogeneity between individuals regarding IGF-I levels within the broad 'normal' range may require re-assessment.
...
PMID:Circulating IGF-I: New Perspectives for a New Century. 1032 7


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

---