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)

Cerebrovascular and cardiovascular diseases are important predictors for survival in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and account for about half the deaths in these patients. Lipoprotein(a) [Lp(a)] is known to show high values in diabetics with proteinuria, and albuminuric renal disease. The purpose of this study was to determine Lp(a) levels and to investigate the association of Lp(a) and atherosclerotic risk factors in patients treated by CAPD. Lp(a) concentration were measured in 20 CAPD patients in the age range 31 to 83 years. Mean (+/- SD) levels of serum Lp(a) were elevated in the CAPD patients compared to age, sex matched 17 controls (49.5 +/- 27.7 vs. 15.5 +/- 12.4 mg/dl, p < 0.001). The levels of Lp(a) were significantly higher in the diabetic CAPD patients than in non-diabetics. There were significant positive correlations between serum Lp(a) concentrations and fasting blood sugar. However, when the above two groups were matched for age, sex, body mass index and FBS, Lp(a) concentrations were also significantly higher in CAPD patients than those in normal controls. We found no statistically significant correlations of Lp(a) with either age, body mass index, blood pressure, serum lipoprotein, apoprotein, glycated hemoglobin, BUN, creatinine or serum protein levels. There were no correlations between serum Lp(a) levels and albumin and LP(a) concentrations in the dialysate in all CAPD patients. Along with assessment of other known established cardiovascular risk factors such as elevated blood pressure, atherogenic abnormalities of plasma lipids and lipoproteins, and impaired glucose tolerance, we suggest that elevated levels of Lp(a) may lead to the accelerated atherosclerosis in these patients.
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PMID:[Alterations of Lp (a) lipoprotein in patients with chronic renal failure treated by continuous ambulatory peritoneal dialysis]. 837 89

The effect of FK409, a new nitric-oxide (NO) donor, on neointimal formation of rat carotid arteries following balloon injury was studied. The intimal thickening at 14 days was strongly suppressed by twice daily administration of FK409 at 10 mg/kg from 2 days before to 13 days after injury. The neointima area and neointima/media ratio were decreased by 48.0% (P < 0.01) and 38.5% (P < 0.01), respectively, compared with control. On the other hand, isosorbide dinitrate (ISDN), a classical nitro-vasodilator, did not suppress intimal thickening even at 100 mg/kg twice a day. An in vivo 5-bromo-2'-dedoxyuridine (BrdU) uptake study revealed that FK409 inhibited the proliferative response of smooth muscle cells (SMC) in media at early stage of injury. In fact, the neointimal formation at 14 days was inhibited by the short term administration of FK409 only from the day of injury to 4 days after at 10 mg/kg twice a day. In cultured rat SMC, FK409 (1-10 mumol/l) markedly enhanced intracellular c-GMP and inhibited the proliferation in 10% FBS-containing medium. These results suggest that FK409 suppresses intimal thickening following balloon injury of the rat carotid artery by inhibition of SMC proliferation.
Atherosclerosis 1995 Sep
PMID:FK409, a new nitric-oxide donor, suppresses smooth muscle proliferation in the rat model of balloon angioplasty. 854 59

Prebeta HDL are small, protein rich lipoproteins that are predominantly composed of apo A-I, without apo A-II. Prebeta HDL are secreted from the liver as nascent HDL and/or are produced in the incubated plasma by cholesteryl ester transfer protein (CETP). However, the role of CETP in the secretion of HDL from the liver has yet to be determined. In the present study, we examined the effect of the suppression of hepatic CETP by antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the secretion of apo A-I using a Hep G2 cell culture. The ODNs against CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method for the regulation of liver gene expression. Hep G2 cells were cultured in DMEM supplemented with 10 FBS. After 2 days, the medium was changed to DMEM with EGF and the cells were divided into three groups. The control group received saline, while the sense group was mixed with the sense ODNs complex and the antisense group was mixed with the antisense ODNs complex, respectively, for 2 days. Both the hepatic CETP mRNA and the CETP mass in the medium in the antisense group decreased significantly more than in the sense and the control groups (CETP mass: 1.697 + /- 0.410 ng/mg cell protein vs. 2.367 + /- 0.22 and 2.360 + /- 0.139, n = 3 in each determination). In contrast, both the hepatic apo A-I mRNA and the apo A-I mass in the medium in the antisense group were significantly higher than those in the sense and the control groups (apo A-I mass; 1.877 + /- 0.215 micro/mg cell protein vs. 1.213 + /- 0.282 and 1.097 + /- 0.144, n = 3 in each determination). The increase in apo A-I was mainly due to the increase in prebeta apo A-I. These findings may partly explain why HDL and apo A-I increase in patients with CETP deficiency, while also indicating the possibility that the original level of prebeta HDL is sufficient in such patients.
Atherosclerosis 1999 Oct
PMID:Secretion of prebeta HDL increases with the suppression of cholesteryl ester transfer protein in Hep G2 cells. 1053 85

Several large epidemiological studies have shown a correlation between elevated plasma carotenoid levels and decreased risk of cardiovascular disease (CVD). One proposed mechanism for the beneficial effect of carotenoids is through functional modulation of potentially atherogenic processes associated with the vascular endothelium. To test this, we incubated confluent human aortic endothelial cell (HAEC) cultures (passages 4-8) for 24 h with each of the five most prevalent carotenoids in human plasma, which are alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene, at an approximate concentration of 1 micromol/l. Carotenoids were solubilized in 0.7% (v/v) tetrahydrofuran and incorporated into FBS before adding to cell culture medium. Due to disparate solubilities in aqueous medium, final concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene were 1.7, 1.1, 0.7, 0.9, and 0.3 micromol/l and monolayers accumulated 647, 158, 7, 113, and 9 pmol/mg protein, respectively. Monolayers were then stimulated with IL-1beta (5 ng/ml) for 6 h with subsequent determination of cell surface expression of adhesion molecules as measured by an enzyme-linked immunosorbent assay (ELISA). To assess endothelial cell adhesion to monocytes, IL-1beta-stimulated monolayers were incubated for 10 min with 51Cr-labeled U937 monocytic cells and adhesion determined by isotope counting. Pre-incubation of HAEC with beta-carotene, lutein and lycopene significantly reduced VCAM-1 expression by 29, 28, and 13%, respectively. Pre-incubation with beta-carotene and lutein significantly reduced E-selectin expression by 38 and 34%, respectively. Pre-treatment with beta-carotene, lutein and lycopene significantly reduced the expression of ICAM-1 by 11, 14, and 18%, respectively. While other carotenoids were ineffective, lycopene attenuated both IL-1beta-stimulated and spontaneous HAEC adhesion to U937 monocytic cells by 20 and 25%, respectively. Thus, among the carotenoids, lycopene appears to be most effective in reducing both HAEC adhesion to monocytes and expression of adhesion molecules on the cell surface.
Atherosclerosis 2000 Jun
PMID:The effect of carotenoids on the expression of cell surface adhesion molecules and binding of monocytes to human aortic endothelial cells. 1085 18

The growth-promoting effects of insulin-like growth factor-I (IGF-I) appear to be different in vascular smooth muscle cells from various segments of the arterial tree. Little information exists on human coronary artery smooth muscle cells (CoSMC), the primary elements of coronary atherosclerosis and post-angioplasty restenosis. In this study we determined the effects of IGF-I on cultured human CoSMC. Type I IGF receptors (IGF-R) were present on CoSMC as assessed by affinity cross-linking of 125I-IGF-I to monolayer cultures. IGF-I was a weak mitogen, 1.5-fold increase in [3H]thymidine incorporation, for CoSMC. However, IGF-I had a potent motility effect on CoSMC with a 314+/-12% increase in cell migration (P<0.001), comparable to that of 5% FBS. IGF-I-stimulated motility was partially inhibited by alphaIR-3, a specific IGF-R inhibitor (P<0.05). Addition of kistrin, a disintegrin, or LM609, a specific alpha(V)beta(3) integrin neutralizing antibody, abolished IGF-I-stimulated migration (P<0.001). This study indicates that IGF-I is a potent motility agent for human CoSMC via the alpha(V)beta(3) integrin receptor, but exerts little mitogenic effect. Because CoSMC migration plays a crucial role in atherosclerosis and restenosis, IGF-I blockade has the potential to limit lumen reduction.
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PMID:Effects of insulin-like growth factor-I on cultured human coronary artery smooth muscle cells. 1293 45

Pyrrolidine dithiocarbamate (PDTC), a metal chelating compound, is known to induce cell death in vascular smooth muscle cells (VSMC). However, the molecular mechanism for PDTC-induced VSMC death is not well understood. Addition of PDTC reduced cell growth and DNA synthesis on VSMC in low density conditions. However, in serum depleted medium, PDTC did not affect the cell viability, suggesting that certain factors in serum may mediate the cytotoxic effect of PDTC. Several metal chelators prevented the cell death induced by PDTC. In a serum-deprived condition, addition of exogenous metals, copper, iron, and zinc, restored the cytotoxic effect of PDTC. These data indicate that metals such as copper, iron, and zinc in serum may mediate the cytotoxic effect of PDTC. At low VSMC density in 10% FBS, treatment of PDTC, which induced a cell-cycle block in G1-phase, induced down-regulation of cyclins and CDKs and up-regulation of the CDK inhibitor p21 expression, whereas up-regulation of p27 or p53 by PDTC was not observed. Finally, we determined PDTC-mediated signaling pathway involved in VSMC death. Among relevant pathways, PDTC induced marked activation of p38MAPK and JNK. Expression of dominant negative p38MAPK and SB203580, a p38MAPK specific inhibitor, blocked PDTC-dependent p38MAPK, growth inhibition, and p21 expression. These data demonstrate that the p38MAPK pathway participates in p21 induction, which consequently leads to decrease of cyclin D1/cdk4 and cyclin E/cdk2 complexes and PDTC-dependent VSMC growth inhibition. In conclusion, an understanding of the molecular mechanisms of PDTC in VSMC provides a theoretical basis for clinical approaches using antioxidant therapies in atherosclerosis.
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PMID:PDTC, metal chelating compound, induces G1 phase cell cycle arrest in vascular smooth muscle cells through inducing p21Cip1 expression: involvement of p38 mitogen activated protein kinase. 1460 33

Proliferation of vascular smooth muscle cells stimulated by reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture medium were studied over 3 d in the presence or absence of a free radical scavenger, edaravone. Viability of cells at the end of incubation was measured by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Results demonstrated that fluvastatin and amlodipine by themselves possess antiproliferative effects on the GBa-SM3 cells at 10-100 microM and 0.1-1 microM, respectively. While edaravone possessed no antiproliferative effect by itself at 100 microM, it significantly (p<0.05) augmented the antiproliferative effects of fluvastatin and amlodipine. In addition, ozagrel, GF109203X and Y27632 possessed no appreciable effects on the cell growth by themselves. However, coincubation of edaravone at 100 microM with these agents elicited significant antiproliferative effects for ozagrel, GF109203X and Y27632 at 10-100 microM, 1-10 microM and 0.1-1 microM, respectively. In conclusion, edaravone may have clinically beneficial interactions with fluvastatin, amlodipine and ozagrel regarding the prevention of vascular atherosclerosis. The interactions between edaravone and the inhibitors of protein kinase C and ROCK were suggestive of possible contributions of ROS-triggered intracellular signals associated with these enzymes to vascular atherogenesis, but further studies are required for confirmation.
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PMID:Edaravone, a radical scavenger, may enhance or produce antiproliferative effects of fluvastatin, amlodipine, ozagrel, GF109203X and Y27632 on cultured basilar artery smooth muscle cells. 1464 75

Labedipinedilol-A is a novel 1, 4-dihydropyridine type calcium antagonist with alpha-receptor blocking activity. This study investigates the effects of labedipinedilol-A on mitogen-induced proliferation of rat vascular smooth muscle cells (VSMCs). Labedipinedilol-A's inhibition on cell proliferation was measured by the tetrazolium salt (XTT) test. Labedipinedilol-A dose-dependently inhibited mitogen-induced DNA synthesis, determined by the incorporation of 5-bromo-2'-deoxyuridine (BrdU). Labedipinedilol-A was also found capable of inhibiting the migration of VSMCs induced by PDGF-BB with an IC50 value of 5.6 microM. In accordance with these findings, labedipinedilol-A revealed blocking of the FBS-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Labedipinedilol-A appeared to cause inhibition of mitogens-induced PKC translocation, suggesting the probable involvement of protein kinase C (PKC) in this cellular response. Labedipinedilol-A reduced both intracellular Ca and the phosphorylation of extracellular signal-regulated protein kinase 1/2 in PDGF-BB-stimulated VSMCs. It also suppressed the levels of proliferative cell nuclear antigen (PCNA) in VSMCs both time- and dose-dependently. These results indicate that labedipinedilol-A may inhibit cell proliferation by attenuating activation of the ERK 1/2 pathway, which is regulated by PKC and Ca, suggesting that it may have great potential in the prevention of progressive atherosclerosis.
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PMID:Inhibition of mitogen-mediated proliferation of rat vascular smooth muscle cells by labedipinedilol-A through PKC and ERK 1/2 pathway. 1550 90

Greater fish oil consumption has been associated with reduced CVD risk, although the mechanisms are unclear. Plant-source oil omega-3 fatty acids (ALA) have also been studied regarding their cardiovascular effect. We conducted a systematic review of randomized controlled trials that evaluated the effect of consumption of fish oil and ALA on commonly measured serum CVD risk factors, performing meta-analyses when appropriate. Combining 21 trials evaluating lipid outcomes, fish oil consumption resulted in a summary net change in triglycerides of -27 (95% CI -33, -20)mg/dL, in HDL cholesterol of +1.6 (95% CI +0.8, +2.3)mg/dL, and in LDL cholesterol of +6 (95% CI +3, +8)mg/dL. There was no effect of fish oil on total cholesterol. Across studies, higher fish oil dose and higher baseline levels were associated with greater reductions in serum triglycerides. Overall, the 27 fish oil trials evaluating Hgb A(1c) or FBS found small non-significant net increases compared to control oils. Five studies of ALA were inconsistent in their effects on lipids, Hgb A(1c) or FBS. Four studies investigating the effects of omega-3 fatty acids on hs-CRP were also inconsistent and non-significant. The evidence supports a dose-dependent beneficial effect of fish oil on serum triglycerides, particularly among people with more elevated levels. Fish oil consumption also modestly improves HDL cholesterol, increases LDL cholesterol levels, but does not appear to adversely affect glucose homeostasis. The evidence regarding the effects of omega-3 fatty acids on hs-CRP is inconclusive, as are data on ALA.
Atherosclerosis 2006 Nov
PMID:Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. 1653 Feb 1

Hyperlipidemia is one of the famous disorders that can lead to atherosclerosis. Garlic has been considered as one of the blood lipids lowering agents for ages, and various studies have been carried out, some of them confirmed this effect of garlic and some did not. The aim of this study was to evaluate the effect of raw garlic consumption on human blood biochemical factors in hyperlipidemic individuals. This clinical trial was conducted on 30 volunteer individuals with blood cholesterol higher than 245 mg/dl. Fasting blood samples were collected for biochemical tests. The volunteers consumed 5 g raw garlic twice a day for 42 days. Second fasting blood samples were collected and the individuals did not use any kind of garlic for next 42 days. After that, the third fasting blood samples were collected and the biochemical factors were measured. After 42 days of garlic consumption the mean of blood total cholesterol (p<0.001) triglycerides (p<0.01) and FBS (p<0.01) were reduced significantly, but HDL-C was increased (p<0.001) significantly. Following 42 days of no garlic consumption total cholesterol (p<0.001), triglycerides and FBS (p<0.05) were significantly increased and HDL-C (p<0.01) decreased. Garlic consumption alone can decrease serum lipids, but it cannot be used as the main therapeutic agent for hyperlipidemia. Garlic can be used in mild hyperlipidemia or when the patients cannot tolerate the chemical drugs.
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PMID:Study of the effects of raw garlic consumption on the level of lipids and other blood biochemical factors in hyperlipidemic individuals. 1710 7


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