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)

Advances in molecular biology and medical biotechnology are continuously creating exciting possibilities for DNA based diagnostics. It is now possible by simple procedures to detect polymorphic DNA markers, structural variants and regulatory mutants of human genes, allowing detailed genotyping of patients. The innovative combination of immunoenzymatic techniques, monoclonal antibodies and recombinant tracer proteins, results in new DNA based tests for the determination of important biochemical parameters, in order to define more precisely the phenotype and hence assess the individual risk. The application of these technologies to the analysis of dyslipidemias, atherosclerosis and cardiovascular diseases may not only lead to a better understanding of the molecular and genetic basis of these pathologies, but also to their early recognition and better management.
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PMID:DNA based diagnostic tests: recombinant DNA and cardiovascular disease risk factors. 210 Jun 92

We have investigated whether any of the three isoforms of endothelin (ET) ET-1, ET-2 and ET-3 or the structurally similar peptide sarafotoxin S6b is mitogenic on its own for rat vascular smooth muscle cells in culture. DNA synthesis was determined by a peroxidase-linked double antibody technique to detect bromodeoxyuridine incorporation into the nucleus and stained nuclei were counted by image analysis. None of the ET peptides or sarafotoxin S6b (up to 100 nM) was capable of initiating DNA synthesis in the absence of platelet derived growth factor (PDGF) or fetal calf serum. All the peptides potentiated the mitogenic effect of low concentrations of PDGF. ET-1 and ET-2 (10 nM) caused a 2-fold increase in the number of stained nuclei induced by 5 nM and 10 nM PDGF, whereas ET-3 and sarafotoxin S6b were less potent. These findings demonstrate that ET is a co-mitogen for rat vascular smooth muscle cells. The release of ET at sites of endothelial injury may therefore enhance the mitogenic action of locally acting PDGF on vascular smooth muscle cells and potentiate the proliferative response.
Atherosclerosis 1990 Dec
PMID:The endothelin peptides ET-1, ET-2, ET-3 and sarafotoxin S6b are co-mitogenic with platelet-derived growth factor for vascular smooth muscle cells. 210 88

A recombinant beta-galactosidase gene has been expressed in a specific arterial segment in vivo by direct infection with a murine amphotropic retroviral vector or by DNA transfection with the use of liposomes. Several cell types in the vessel wall were transduced, including endothelial and vascular smooth muscle cells. After retroviral infection, a recombinant reporter gene was expressed for at least 5 months, and no helper virus was detected. Recombinant gene expression achieved by direct retroviral infection or liposome-mediated DNA transfection was limited to the site of infection and was absent from liver, lung, kidney, and spleen. These results demonstrate that site-specific gene expression can be achieved by direct gene transfer in vivo and could be applied to the treatment of such human diseases as atherosclerosis or cancer.
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PMID:Site-specific gene expression in vivo by direct gene transfer into the arterial wall. 211 55

The effects of thromboxane A2 (TXA2) on the proliferation of vascular smooth muscles cells (VSMC) were examined using primary cultures of VSMC from rat aorta. U46619, a stable TXA2 mimetic, stimulated DNA synthesis of VSMC only in the presence of insulin. The effect was concentration-dependent with a half-maximal effect obtained at approximately 1 x 10(-8) M. The mitogenic effect of U46619 was larger than that of endothelin, another mitogen derived from endothelium. Among several TXA2/PGH2 analogs, the proliferative activity was detected only in the agonists, and not in the antagonists or in the metabolite of TXA2. A series of TXA2/PHG2 receptor antagonists completely suppressed the U46619-stimulated DNA synthesis as well as the [3H]SQ29,548 binding to the TXA2/PGH2 receptors in VSMC. The rank order of binding affinities to the receptors among the respective antagonists correlated well with the potencies for suppression of the proliferative effects of U46619. The mitogenic effects of U46619 were also attenuated by the presence of calcium antagonists. U46619 caused activation of phospholipase C with the production of inositol trisphosphate, leading to increases in the intracellular free Ca2+ concentration as measured with the fluorescent indicator fura-2. These results suggest that TXA2 induces mitogenic effects on VSMC through binding to its specific receptors. This effect of TXA2 on the proliferation of VSMC may be related to the development of atherosclerosis.
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PMID:Receptor-mediated mitogenic effect of thromboxane A2 in vascular smooth muscle cells. 214 80

The presence of cytomegalovirus (CMV) nucleic acids was demonstrated in arterial walls of patients with grade III and with maximally grade I atherosclerosis by dot blot and in situ DNA hybridization and by polymerase chain reaction (PCR) using probes and primers derived from immediate early (IE) and late (L) genomic regions. The presence of the complete viral genome could be demonstrated by both dot blot DNA hybridization and PCR. IE mRNA but not L mRNA could be demonstrated by in situ DNA hybridization, indicating the presence of latent CMV in the human arterial wall. By PCR 90% of the samples obtained from atherosclerotic patients were shown to contain viral nucleic acids as compared to 53% of patients with maximally grade I atherosclerosis, thus substantiating a role for this virus in the pathogenesis of atherosclerosis.
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PMID:High prevalence of latently present cytomegalovirus in arterial walls of patients suffering from grade III atherosclerosis. 215 48

A method is described for the quantification of vascular smooth muscle cell growth from individual explants of contractile rabbit aortic tunica media. The precision of the method probably depends on regular explant geometry (1-mm squares) and pooling sufficient explants. Serum-induced growth was quantified by measurements of ATP concentration, incorporation of [3H]thymidine and DNA concentration. The possible effects of endogenous vasodilator agents on growth were investigated by using lipid soluble analogues of their second messengers, namely 8-Br-cAMP and 8-Br-cGMP, which are known to relax rabbit aortic strips. Cell growth was inhibited concentration-dependently by 8-Br-cAMP but not 8-Br-cGMP (0.01-1 mM). The effect of 8-Br-cAMP was reversible, and also occurred when addition was delayed until after growth had commenced. The results imply that endogenous vasodilators such as prostacyclin, adenosine and adrenaline, which increase cAMP concentration, may normally suppress smooth muscle cell growth, whereas nitric oxide and atriopeptins, which increase cGMP concentration, may not.
Atherosclerosis 1990 May
PMID:Serum-induced proliferation of rabbit aortic smooth muscle cells from the contractile state is inhibited by 8-Br-cAMP but not 8-Br-cGMP. 216 52

Whole blood serum (WBS) rapidly induced the phospholipase C-mediated hydrolysis of phosphoinositides and subsequently stimulated DNA synthesis in cultured rabbit vascular smooth muscle cells (VSMCs). Ketanserin, a serotonin (S2) receptor antagonist, markedly inhibited the WBS-induced phospholipase C reaction and DNA synthesis. Serotonin by itself had a weak mitogenic activity for VSMCs, but this vasoconstrictor markedly stimulated the platelet-derived growth factor- and epidermal growth factor-induced DNA synthesis. The stimulatory effect of serotonin on the growth factor-induced DNA synthesis was inhibited by ketanserin. The amount of serotonin contained in WBS was sufficient to induce the phospholipase C reaction and stimulate the growth factor-induced DNA synthesis. These results indicate that serotonin plays a major role in the WBS-induced phospholipase C-mediated hydrolysis of phosphoinositides and DNA synthesis in rabbit VSMCs and suggest that serotonin may act as an important growth regulator for VSMCs in addition to acting as a vasoconstrictor.
Atherosclerosis 1990 Jul
PMID:Serotonin plays a major role in serum-induced phospholipase C-mediated hydrolysis of phosphoinositides and DNA synthesis in vascular smooth muscle cells. 216 88

Variations in the DNA sequence flanking the 5' region of the human insulin gene (U- and L-alleles) were studied in relation to atherosclerosis, lipid levels, and age in three groups of atherosclerotic individuals and in nonatherosclerotic controls. The atherosclerotic groups comprised a postmyocardial infarction group with a mean age of 48 years, a group of individuals operated on for carotid stenosis with a mean age of 62 years, and a group of 85-year-olds with clinical coronary disease, peripheral arterial disease, or both. All 331 individuals were unrelated Caucasians of Danish ancestry. There were no significant differences (p greater than 0.05) in genotype distribution or allele frequencies between atherosclerotic and nonatherosclerotic individuals, but in the 85-year-olds, there was evidence (p less than 0.10) for a lower U-allele frequency in nonatherosclerotic women compared to atherosclerotic women. In nonatherosclerotic women, there was a significant decrease in U-allele frequency with age (60 to 85 years). This decrease does not prove conclusively, but is compatible with, the hypothesis that the U-allele predisposes to, or the L-allele protects against, atherosclerosis. The possible effect of the U-allele on the development of atherosclerosis does not seem to be mediated through conventional risk factors.
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PMID:Polymorphism in 5' flanking region of human insulin gene. Relationships with atherosclerosis, lipid levels, and age in three samples from Denmark. 218 39

It is widely reported that cultured vascular smooth muscle cells (CVSMCs) from spontaneously hypertensive rats (SHR) show enhanced proliferation compared with cells from Wistar-Kyoto rats (WKY). The present studies were designed to find out whether this exaggerated proliferation in SHR is determined genetically and, if so, to evaluate the mechanism on the cell cycle. (1) Incorporation of [3H]thymidine into DNA was enhanced in CVSMCs from 3- and 12-week-old SHR compared with WKY but not in CVSMCs from DOCA-salt hypertensive rats compared with the cells from sham-operated rats. (2) DNA synthesis in SHR cells was enhanced further by addition of insulin (which is considered to be a progression factor) but not by arginine-vasopressin (AVP; considered to be a competence factor) or by angiotensin II (AII). On the other hand, insulin, AVP and AII significantly augmented DNA synthesis in WKY cells. (3) Intracellular free calcium concentration was slightly, but significantly, higher in SHR cells. (4) An increase in the population of DNA-synthesizing S-phase cells and decrease in (G2 + M)-phase cells in SHR were observed by flowcytometry. These data suggest (1) that enhanced DNA synthesis in CVSMCs from SHR is determined genetically, (2) that enhanced DNA synthesis in CVSMCs from SHR is largely dependent on an increased proportion of S-phase cells and (3) that this increase in S-phase cells in CVSMCs from SHR could be due to enhanced competence gene expression in SHR cells. (4) The increased intracellular free calcium concentration is compatible with an activation of the inositol-trisphosphate pathway.
Atherosclerosis 1990 Apr
PMID:Enhanced DNA synthesis of cultured vascular smooth muscle cells from spontaneously hypertensive rats. Difference of response to growth factor, intracellular free calcium concentration and DNA synthesizing cell cycle. 219 May 64

To evaluate the effect of hypertension on glycosaminoglycan (GAG) synthesis, cultured vascular smooth muscle cells (CVSMCs) from the aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were exposed to centrifugal forces and catecholamines. GAG synthesis of CVSMCs was measured by the incorporation of [3H]glucosamine into GAGs which were secreted into the culture medium for 24 h. Basal level of GAG synthesis was much higher in SHR than in WKY, when expressed in terms of DNA contents. When exposed to centrifugal force, CVSMCs from rats of both strains synthesized more GAGs. GAG synthesis was enhanced by both noradrenaline (NA) and adrenaline (Ad) in WKY. The enhanced GAG synthesis in WKY by NA or Ad was prevented by pretreatment with propranolol, but not prazosin. In SHR, NA and Ad did not enhance GAG synthesis at this concentration of catecholamines. However, the effects of propranolol or prazosin on GAG synthesis in SHR, when incubated with either NA or Ad, were compatible with the phenomena observed in WKY. Adding dibutyryl cyclic AMP to the culture medium enhanced GAG synthesis in rats of both strains. These data suggest that not only the mechanical stress of high intra-arterial pressure but also beta receptor stimulation, via increasing cyclic AMP, enhance GAG synthesis of vascular smooth muscle cells in hypertension.
Atherosclerosis 1990 Aug
PMID:Effect of centrifugal force and catecholamines on glycosaminoglycans synthesis of vascular smooth muscle cells in culture. 224 93


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