UMLS:C0004153 - FACTA Search

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

The present study was designed in order to: (a) compare ET-1 and ADMA levels, between women with PCOS (n=106) and healthy controls (n=30); (b) determine the effects of treatment with estrogens and anti-androgens on the hormonal features of PCOS, insulin resistance, ET-1 and ADMA levels. Women with PCOS were randomized in five therapeutic protocols: (I) 17beta-estradiol+cyproterone acetate 50mg; (II) conjugated estrogen+CA 50 mg; (III) ethinyl estradiole+CA 2mg; (IV) EE+CA 52 mg; (V) EE+desogestrel. In all women, gonadotropin, PRL, androgen, SHBG, insulin, glucose, ET-1 and ADMA levels were determined; in women with PCOS, testosterone, SHBG, ET-1 and ADMA levels were measured again after 3, 6, 12 months of treatment and insulin and glucose levels after 12 months. ET-1 and ADMA concentrations were higher in women with PCOS, and they were positively correlated with each other. ADMA levels were decreased and IR was increased with treatment. Treatment with synthetic estrogens (EE) resulted in a more pronounced increase in SHBG and a more pronounced decrease in FAI, compared to natural estrogens. Conclusively, PCOS is associated with endothelial dysfunction, which is ameliorated by the administration of estrogens and anti-androgens, independent of IR.
Atherosclerosis 2008 Feb
PMID:The administration of estrogens, combined with anti-androgens, has beneficial effects on the hormonal features and asymmetric dimethyl-arginine levels, in women with the polycystic ovary syndrome. 1741 49

Observations have been made linking the presence of psychosocial factors associated with elevated beta-endorphin concentrations with atherosclerosis. In this study, the authors assume an important role of the stress hormone beta-endorphin in several mechanisms that contribute to a dysbalance of human endothelial and monocytic endothelin (ET)-1 and nitric oxide (NO) release, mediated by mu1-opioid receptors. ET-1 and NO release were quantified via enzyme-linked immunosorbent assay (ELISA) or fluorometrically. mu1-Opioid receptors were identified by polymerase chain reaction (PCR) after stimulation with beta-endorphin. beta-Endorphin significantly increased endothelial and monocytic ET-1 release. The effect was mediated by mu1-opioid receptors and abolished by naloxonazine, a selective mu1-opioid receptor antagonist. In contrast, NO release was decreased under the influence of beta-endorphin. mu1-Opioid receptors on human monocytes and endothelial cells mediated a beta-endorphin-induced stimulation of ET-1 release, whereas NO release was decreased. Thus, the authors hypothesize a role of beta-Endorphin in the pathogenesis of stress-induced endothelial dysfunction through peripherally circulating beta-endorphin, which may offset the balance of vasoactive mediators, leading to an unopposed vasoconstriction. The data may also provide a new concept of mu1-opioid receptor antagonists, preventing beta-endorphin-induced disorders of vascular biology.
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PMID:Effects of beta-endorphin on endothelial/monocytic endothelin-1 and nitric oxide release mediated by mu1-opioid receptors: a potential link between stress and endothelial dysfunction? 1749 62

Development of a cultured tissue experimental model of rat aorta was explored in order to study mechanism of vascular smooth muscle (VSMC) proliferation. This particular model has potential with regard to amelioration of atherosclerosis and other vascular diseases in comparison to whole animal and cell culture models. The aorta segments of rats were divided into 4 experimental groups: the injured endothelium, injured endothelium plus BQ123, without injured endothelium and without injured endothelium plus BQ123. Each of group was subdivided into a further 2 subgroups and cultured with 20% serum and with serum-free DMEM. Each group cultured in vitro for 5, 8 and 13 days respectively. The control group was not cultured in vitro. Bromodeoxyuridine (BrDU 8x10(-4) mol/l) was added into the cultured medium of all groups, 24 h prior to harvesting. These segments were fixed in 4% paraformaldehyde for paraffin slice used to HE and immunocytochemical staining and other aorta segments were used to detect the expressions of hypertension-related gene-1 (HRG-1) and smooth muscle 22 alpha (SM22alpha) by RT-PCR. ET-1 content in the supernatant was detected with radioimmunology. Proliferous VSMC can be observed on artery segments cultured in vitro, and conspicuous plaques were developed on model vascular wall cultured for 13 days. Labeled cells increased with an increase in culture time but were not seen in the control group. A greater number of labeled cells were observed in injured endothelium group cultured in 20% serum DMEM. Hyperplasia was inhibited after BQ123 was added into the medium, suggesting that serum and ET-1 are important factors that lead to VSMC proliferation. Expressions of HRG-1 and SM22alpha were decreased while the aorta segments were cultured in vitro, minimum or even absent mRNA expressions of HRG-1 and SM22alpha were detected in injured endothelium cultured in 20% serum DMEM and increased in injured endothelium plus BQ123 group cultured. ET-1 content in the supernatant increased in injured endothelium cultured in 20% serum DMEM. These results show that the phenotypic transform and VSMC proliferation on cultured artery segments were related not only to serum culture, but also to ET-1 secreting. ET-1 and serum may be the main factors of contributing to the proliferation and phenotypic transform. This model provides a favorable experimental platform for research into the mechanism of vascular proliferous diseases as well as its prevention and treatment.
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PMID:A novel cultured tissue model of rat aorta: VSMC proliferation mechanism in relationship to atherosclerosis. 1793 23

Oxidative stress plays a crucial role in the pathogenesis of atherosclerosis by promoting endothelial dysfunction and impairing vascular relaxation. Flavonoids are largely investigated for their biological properties and particularly for their scavenging and antioxidant properties. In the current study, we evaluated the clastogenicity of the chalcone plicatin B in peripheral human lymphocytes (whole blood and pure lymphocytes) as well as its antioxidant activity and its ability to contrast dysfunction on human microvascular endothelial cells (HMEC-1) exposed to hydrogen peroxide. We measured in the cell culture medium the levels of 8-isoprostane, NOx, ET-1, and ICAM-1, as well as the expression of e-NOS, prepro-ET-1, and ICAM-1. In conclusion, our results demonstrate that the chalcone plicatin B (1-10 microM) may represent a good candidate for the prevention of atherosclerosis, as it consistently reduces the oxidative/inflammatory process and is not genotoxic to human lymphocytes.
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PMID:Antioxidant activity of plicatin B on cultured human microvascular endothelial cells exposed to H2O2. 1793 21

Prostanoids are cyclic lipid mediators which arise from enzymic cyclooxygenation of linear polyunsaturated fatty acids, e.g. arachidonic acid (20:4 n 6, AA). Biologically active prostanoids deriving from AA include stable prostaglandins (PGs), e.g. PGE(2), PGF(2alpha), PGD(2), PGJ(2) as well as labile prostanoids, i.e. PG endoperoxides (PGG(2), PGH(2)), thromboxane A(2) (TXA(2)) and prostacyclin (PGI(2)). A "Rabbit aorta Contracting Substance" (RCS) played important role in discovering of labile PGs. RCS was discovered in the Vane's Cascade as a labile product released along with PGs from the activated lung or spleen. RCS was identified as a mixture of PG endoperoxides and thromboxane A(2). Stable PGs regulate the cell cycle, smooth muscle tone and various secretory functions; they also modulate inflammatory and immune reactions. PG endoperoxides are intermediates in biosynthesis of all prostanoids. Thromboxane A(2) (TXA(2)) is the most labile prostanoid (with a half life of 30 s at 37 degrees C). It is generated mainly by blood platelets. TXA(2) is endowed with powerful vasoconstrictor, cytotoxic and thrombogenic properties. Again the Vane's Cascade was behind the discovery of prostacyclin (PGI(2)) with a half life of 4 min at 37 degrees C. It is produced by the vascular wall (predominantly by the endothelium) and it acts as a physiological antagonist of TXA(2). Moreover, prostacyclin per se is a powerful cytoprotective agent that exerts its action through activation of adenylate cyclase, followed by an intracellular accumulation of cyclic-AMP in various types of cells. In that respect PGI(2) collaborates with the system consisting of NO synthase (eNOS)/nitric oxide free radical (NO)/guanylate cyclase/cyclic-GMP. Both cyclic nucleotides (c-AMP and c-GMP) act in synergy as two energetic fists which defend the cellular machinery from being destroyed by endogenous or exogenous aggressors. Recently, a new partner has been recognized in this endogenous defensive squadron, i.e. a system consisting of heme oxygenase (HO-1)/carbon monoxide (CO)/biliverdin/biliverdin reductase/bilirubin. The expanding knowledge on the pharmacological steering of this enzymic triad (PGI(2)-S/eNOS/HO-1) is likely to contribute to the rational therapy of many systemic diseases such as atherosclerosis, diabetes mellitus, arterial hypertension or Alzheimer diseases. The discovery of prostacyclin broadened our pathophysiological horizon, and by itself opened new therapeutic possibilities. Prostacyclin sodium salt and its synthetic stable analogues (iloprost, beraprost, treprostinil, epoprostenol, cicaprost) are useful drugs for the treatment of the advanced critical limb ischemia, e.g. in the course of Buerger's disease, and also for the treatment of pulmonary artery hypertension (PAH). In this last case a synergism between prostacyclin analogues and sildenafil (a selective phosphodiesterase 5 inhibitor) or bosentan (an endothelin ET-1 receptor antagonist) points our to complex mechanisms controlling pulmonary circulation. At the Jagiellonian University we have demonstrated that several well recognised cardiovascular drugs, e.g. ACE inhibitors (ACE-I), statins, some of beta-adrenergic receptor antagonists, e.g. carvedilol or nebivolol, anti-platelet thienopyridines (ticlopidine, clopidogrel) and a metabolite of vitamin PP--N(1)-methyl-nicotinamide--all of them are endowed with the in vivo PGI(2)-releasing properties. In this way, the foundations for the Endothelial Pharmacology were laid.
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PMID:Prostacyclin among prostanoids. 1827 80

Chronic administration of the most abundant dietary flavonoid quercetin exerts antihypertensive effects and improves endothelial function. We have investigated the effects of quercetin and its methylated metabolite isorhamnetin (1-10microM) on endothelial dysfunction and superoxide (O(2*)(-)) production induced by endothelin-1 (ET-1, 10nM). ET-1 increased the contractile response induced by phenylephrine and reduced the relaxant responses to acetylcholine in phenylephrine contracted intact aorta, and these effects were prevented by co-incubation with quercetin, isorhamnetin or chelerythrine (protein kinase C (PKC) inhibitor). This endothelial dysfunction was also improved by superoxide dismutase (SOD), apocynin (NADPH oxidase inhibitor) and sepiapterin (tetrahydrobiopterin synthesis substrate). Furthermore, ET-1 increased intracellular O(2*)(-) production in all layers of the vessel, protein expression of NADPH oxidase subunit p47(phox) without affecting p22(phox) expression and lucigenin-enhanced chemiluminescence signal stimulated by calcium ionophore A23187. All these changes were prevented by both quercetin and isorhamnetin. Moreover, apocynin, endothelium denudation and N(G)-nitro-l-arginine methylester (l-NAME, nitric oxide synthase inhibitor) suppressed the ET-1-induced increase in A23187-stimulated O(2*)(-) generation. Moreover, quercetin but not isorhamnetin, inhibited the increased PKC activity induced by ET-1. Taken together these results indicate that ET-1-induced NADPH oxidase up-regulation and eNOS uncoupling via PKC leading to endothelial dysfunction and these effects were prevented by quercetin and isorhamnetin.
Atherosclerosis 2009 Jan
PMID:Quercetin inhibits vascular superoxide production induced by endothelin-1: Role of NADPH oxidase, uncoupled eNOS and PKC. 1843 24

Urotensin II (U-II) is a powerful vasoconstrictor peptide with a potency greater than that of endothelin 1. Its plasma level correlates positively with body weight and is raised in diabetes, renal failure, hypertension, and other cardiovascular diseases, including congestive heart failure and carotid atherosclerosis. Experimental and clinical studies have revealed increased expression of U-II and U-II receptor (UT) in animals with experimentally induced myocardial infarction, heart failure, and in patients with hypertension, atherosclerosis, and diabetes, suggesting a potential role for U-II in coronary artery disease. Peptide and nonpeptide UT ligands have been shown to be effective in antagonizing the effects of U-II in the cardiovascular system. This article aims to review recent advances in physiology and pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases.
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PMID:Role of urotensin II in atherosclerotic cardiovascular diseases. 1860 80

Plaque rupture and subsequent embolism as well as thrombosis are major causes of acute myocardial infarction and stroke secondary to atherosclerosis. Pai-1, t-PA, TF and ET-1 are thrombosis- and thrombolysis-related factors which play important roles in thrombosis formation and plaque rupture. Since acute myocardial infarction and stroke are more likely to occur between 6 a.m. and 12 p.m. than at another time of the day, we studied the relationship between circadian rhythm and Pai-1, t-PA, TF and ET-1 in normal and atherosclerotic mice. Atherosclerosis was developed in apoE-/- mice fed a normal diet or a high cholesterol diet. The expression of Pai-1, t-PA, TF and ET-1 in the hearts of control C57BL/6J mice and atherosclerotic mice was measured by real-time RT-PCR at different Zeitgeber times (ZT) including ZT0, ZT4, ZT8, ZT10, ZT12, ZT14, ZT16 and ZT20. The expression of Pai-1, t-PA, TF and ET-1 peaked between ZT14 and ZT16 and bottomed at ZT10 in C57BL/6J mice. Their expression in apoE-/- mice fed a normal diet lost circadian rhythm. Their expression in apoE-/- mice fed a high cholesterol diet peaked at ZT4, indicating a reverse circadian rhythm. Our result indicates that circadian changes in the expression of Pai-1, t-PA, TF and ET-1 may be involved in the onset of myocardial infarction and stroke.
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PMID:Circadian rhythm disorder of thrombosis and thrombolysis-related gene expression in apolipoprotein E knock-out mice. 1863 67

Epidemiological studies have reported an inverse association between dietary flavonoid intake and mortality for ischemic heart disease. Quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, but it is rapidly metabolized during absorption by methylation, glucuronidation and sulfation. We have analyzed the vasorelaxant effects and the role on NO bioavailability and endothelial function of quercetin and its conjugated metabolites (quercetin-3-glucuronide, isorhamnetin-3-glucuronide and quercetin-3'-sulfate) in rat aorta. Thoracic aortic rings isolated from Wistar rats were mounted for isometric force recording and endothelial function was tested by measuring the vasorelaxant response to acetylcholine. NADPH-enhanced O(2)(-) release was quantified in homogenates from cultured aortic smooth muscle cells using lucigenin chemiluminescence. Unlike quercetin, the conjugated metabolites had no direct vasorelaxant effect, and did not modify endothelial function or the biological activity of NO. However, all metabolites (at 10 micromol/L) prevented, at least partially, the impairment of endothelial-derived NO response under conditions of high oxidative stress induced by the SOD inhibitor DETCA. Furthermore, they protected the biological activity of exogenous NO when impaired by DETCA. Quercetin and quercetin-3'-sulfate (>or=10 micromol/L) or quercetin-3-glucuronide (100 micromol/L) inhibited NADPH oxidase-derived O(2)(-) release. Quercetin and quercetin-3-glucuronide (1 micromol/L) prevented the endothelial dysfunction induced by incubation with ET-1. These data indicate, for the first time, that the conjugated metabolites could be responsible for the in vivo protective activity of quercetin on endothelial dysfunction.
Atherosclerosis 2009 May
PMID:Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasorelaxant effects in rat aorta. 1880 86

Endothelial cells are maintaining atherosclerotic signaling mediated by Extracellular Regulated Kinases 1 and 2 (ERK). Signaling gets activated upon stimulation of G protein-coupled receptors mediated by G(q) and G(i/o) proteins subjected to regulation by RGS proteins. The goal of the study was to delineate the specificity of RGS proteins modulating induced ERK phosphorylation. We used stimulated HUVEC, silenced specifically RGS proteins and compared assessed ERK 1/2 activation with immunohistochemical stainings on atherosclerotic plaques. Increased ERK phosphorylation was detected upon stimulation with Phenylephrine (2.6+/-0.1 times over basal), Endothelin-1 (1.8+/-0.2), Dopamine (5.1+/-0.2), TNF (9.8+/-0.7) or IL-4 (3.1+/-0.3). RGS silencing increased activation of ERK 1/2: Phen (RGS3, 5), ET-1 (RGS3, 4), Dopa (RGS3), TNF (RGS2, 3, 4) or IL-4 (RGS2, 3, 4). Immunohistochemically, increased ERK activation was detected on atherosclerotic plaques. This data supports the role of RGS proteins on ERK activation in human atherosclerosis which identifies RGS proteins as new therapeutical targets.
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PMID:Role of endogenous RGS proteins on endothelial ERK 1/2 activation. 1897 18

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