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)

The anti-atherogenic effect of NIP-200 3,5-dimethyl-4,6-diphenyl-tetrahydro-2H-1,3,5-thiadiazine-2-thione ) was studied in experimental models of 1% cholesterol diet (HCD)-fed rabbits. Interference with growth of the animals did not occur in NIP-200-treated rabbits. NIP-200 had no effect on plasma total cholesterol (TC), triglyceride, free cholesterol and phospholipid during the entire experimental period. However, NIP-200 increased high density lipoprotein-cholesterol (HDL-C) at 1, 2, 4 and 6 weeks, although the average rate of increase was not statistically significant. Percentage surface areas of atherosclerotic lesions on the aorta in NIP-200-treated rabbits (26 +/- 6%) was significantly lower than those in HCD-fed rabbits (48 +/- 8%) (P less than 0.05). Histological studies indicated that NIP-200 prevented intimal thickening, proliferation of elastic fibers and fatty necrosis. Thus, NIP-200 prevented the progression of atherosclerosis without affecting the serum TC. The above results suggest that the improvement of lipoprotein metabolism on the arterial wall and the prevention of migration and proliferation of arterial smooth muscle cells may also be important factors in the progression of atherosclerosis.
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PMID:[Anti-atherogenic effect of NIP-200 on the experimental atherosclerosis in cholesterol-fed rabbits]. 155 37

The effect of trapidil on experimental hyperlipemia and atherosclerosis induced by 1% cholesterol diet in SPF male rabbits (JW/KBL) was investigated by the determination of the lipid contents of the plasma and thoracic aorta and examination of morphological changes in the aorta. Trapidil inhibited the increase of total lipid (TL), total cholesterol (TC), free cholesterol (FC) and phospholipid (PL) by the cholesterol diet in all groups. The level of cholesterol (HDL-C) and phospholipid (HDL-PL) in high density lipoprotein (HDL) remained unchanged after the cholesterol diet and trapidil administration. The atherogenic index (TC-HDL-C/HDL-C, PL-HDL-PL/HDL-PL) was improved by the inhibition of TC and PL by the administration of trapidil. A morphological study of the aorta showed that trapidil inhibited lipid deposition. A microscopic observation of the intima by Sudan III stain showed that inhibition of lipid deposition corresponded with the quantity of trapidil administration. An observation of aorta using transmission electron microscopy (TEM) showed that trapidil inhibited the presence of form cells due to HCD. This inhibition corresponded with the quantity of trapidil administration; and no form cells were seen in the 50 mg/kg-administered group. An observation of intima using scanning electron microscopy (SEM) showed that trapidil inhibited the irregularly elevated regions by HCD. The structure of intima in the 50 mg/kg-administered group was similar to that of the control groups. The observation of the head angiogram showed that trapidil improved the stenosis in the lingual and temporal arteries which was caused by HCD.
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PMID:[Effect of trapidil on experimental hyperlipemia and atherosclerosis induced by cholesterol diet in SPF Japanese white rabbits]. 623 Dec 31

We studied the elasticity and endothelium-dependent relaxation (EDR) of the aorta in 1% cholesterol diet (HCD)-fed rabbits. Furthermore, the effects of ethyl all-cis-5,8,11,14, 17-icosapentaenoate (EPA-E) were examined in this model of atherosclerosis. After 12 weeks of feeding with HCD, the animals showed increase in plasma total cholesterol level, formation of atherosclerotic plaque, decrease in aortic elasticity and impairment of EDR to acetylcholine (ACh). The levels of aortic elasticity in HCD-fed rabbits administered orally with EPA-E (300 mg/kg for 12 weeks) were almost the same as those of rabbits fed a normal diet, although EPA-E showed no effects on the plasma total cholesterol level and formation of atherosclerotic plaque in HCD-fed rabbits. On EDR in response to ACh and cyclic GMP formation in the HCD-fed rabbit aorta, EPA-E improved the impairment of these parameters, but not significantly. Therefore, EPA-E had little effect on the endothelium in this model of atherosclerosis, although EPA-E improved the decrease in the aortic elasticity. Because the levels of aortic elasticity showed no significant correlation with the magnitude of EDR to ACh or the size of atherosclerotic plaque, the decrease of aortic elasticity in this model of atherosclerosis was thought to have little relation to the dysfunction of the endothelium.
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PMID:[Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on elasticity and endothelium-dependent relaxation of the aorta in high cholesterol diet-fed rabbits]. 807 89

The hypocholesterolemic and anti-atherogenic properties of sulfamic acid ((2,4,6-tris (1-methylethyl) phenyl) acetyl) 2,6-bis(1-methylethyl) phenyl ester, the ACAT inhibitor, CI-1011, was tested in 120 male F1B hamsters fed a hypercholesterolemic chow-based diet containing 10%, coconut oil and 0.05% cholesterol plus: (i) no drug treatment (HCD); (ii) 3 mg/kg per day (HCD+3): (iii)10 mg/kg per day (HCD+10); (iv) 30 mg/kg per day (HCD+30) of CI-1011; or (v) 500 mg/kg per day of cholestyramine (CSTY). Plasma samples were collected at 8 and 10 weeks for measurement of total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). For the progression studies, animals were euthanized after 10 weeks for aortic fatty streak area and hepatic cholesterol analysis. For the regression study, a cohort of the HCD was treated with 30 mg/kg per day of CI-1011 (regression) for an additional 8 weeks. The HCD+3, HCD+10, HCD+30 and CSTY lowered plasma TC (25, 32, 34 and 32%, respectively), VLDL-C (62, 74, 71 and 75%, respectively), LDL-C (25, 38, 47 and 46%, respectively) and TG (48, 47, 42 and 45%, respectively). All treatments resulted in a significant lowering of aortic fatty streak area (68, 86, 93 and 94%, respectively) and reduction in hepatic cholesteryl esters (57, 65, 67 and 70%, respectively). Regression of aortic fatty streak area was 90% after 8 weeks of HCD+30 treatment. Also during the regression phase, plasma TC, LDL-C and TG were lowered 23, 33 and 47%, respectively, as well as, hepatic cholesteryl esters (76%). Significant correlations between plasma LDL-C concentration and aortic fatty streak area (r=0.62, P < 0.004) in the HCD+10 group, suggest that CI-1101 altered aortic lipid infiltration primarily by its effect on plasma lipids. However the 30 mg/kg per day dose of CI-1011 which additionally reduced aortic fatty streak area by 51% relative to the 10 mg/kg per day dose was only associated with a 14% further decrease in plasma LDL-C. Finally the 10-fold regression of aortic fatty streak area was associated with only a 35% reduction in plasma LDL-C. These exceptions to the lipid-lesion relationship raise the possibility of additional effects of CI-1011, which may occur independent of or in concert with lipoprotein cholesterol lowering. It is concluded that in hypercholesterolemic hamsters, CI-1011 is approximately 50 times more potent than cholestyramine in cholesterol-lowering, reduction and regression of aortic fatty streak area.
Atherosclerosis 1998 Mar
PMID:The ACAT inhibitor, CI-1011 is effective in the prevention and regression of aortic fatty streak area in hamsters. 956 39

Cholazol H (Alpha-Beta Technology, Worcester, MA), a chemically functionalized, insoluble dietary fiber with bile acid sequestrant properties, was studied in 30 male F1 B Golden Syrian hamsters for its effect on plasma lipid concentrations and early atherogenesis in experiment 1. In experiment 2, 30 male Golden Syrian hamsters were studied for the effects on plasma lipids and fecal excretion of bile acids. In experiment 1, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 5% coconut oil and 0.1% cholesterol for 6 weeks. After 6 weeks, hamsters were continued on the diet with either 0% drug (hypercholesterolemic diet [HCD]), 0.5% cholestyramine (CSTY), or 0.5% Cholazol H for 8 weeks. Fasting plasma lipids were measured at weeks 6, 10, and 14, and early atherosclerosis (fatty streak formation) was measured at week 14. Relative to HCD, CSTY and Cholazol H significantly lowered plasma total cholesterol (TC) (-37%, P < .03, and -30%, P < .04, respectively) and plasma very-low and low-density lipoprotein-cholesterol (nonHDL-C) (-45%, P < .02, and -36%, P < .03, respectively) with no significant effects on plasma HDL-C or triglycerides (TG). Despite similar reductions in nonHDL-C, only Cholazol H significantly prevented early atherosclerosis (-38%, P < .02) relative to HCD. In experiment 2, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 10% coconut oil and 0.05% cholesterol and either 0% drug HCD, 0.5% CSTY, or 0.5% Cholazol H for 4 weeks. Fasting plasma lipids were measured at weeks 2 and 4, and fecal bile acids were measured at week 4. Both Cholazol H and CSTY were equally effective in significantly lowering plasma TC (-16%, P < .003, and -13%, P < .01, respectively) and nonHDL-C (-22%, P < .004, and -18%, P < .02, respectively), with no significant effect on HDL-C and TG relative to HCD. Cholazol H and CSTY produced a significantly greater concentration of fecal total bile acids (39%, P < .001, and 28%, P < .002, respectively) relative to HCD. Also, there was a 48% (P < .002) and 65% (P < .001) greater fecal concentration of cholic acid (CA) for Cholazol H-treated hamsters compared with HCD- and CSTY-treated hamsters, respectively. Cholazol H also significantly increased fecal concentration of deoxycholic acid (DCA; 56%, P < .02) compared with HCD. In summary, Cholazol H is as effective as CSTY for prevention of diet-induced hypercholesterolemia and early atherosclerosis in hamsters.
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PMID:The hypocholesterolemic and antiatherogenic effects of Cholazol H, a chemically functionalized insoluble fiber with bile acid sequestrant properties in hamsters. 971 92

Dehydroepiandrosterone (DHEA) is speculated to have an antiatherosclerotic effect, although the mechanism of action remains unclear. The objective of the current study was to determine whether the antiatherosclerotic effect of DHEA is related to its conversion to estrogen and to define the role of nitric oxide (NO) in the antiatherosclerotic effect of DHEA. Forty-eight oophorectomized rabbits were divided into 5 groups and fed the following diets for 10 weeks: group 1, a regular rabbit diet plus 1% cholesterol (a high-cholesterol diet [HCD]); group 2, an HCD plus 0.3% DHEA; group 3, an HCD plus 0.3% DHEA and fadrozole (2.0 mg x kg(-1) x d(-1)), a specific aromatase inhibitor; group 4, an HCD plus 17beta-estradiol (20 microg x kg(-1) x d(-1)); and group 5, a regular diet. Atherosclerotic lesions, lipid deposition in aortic vessels, and basal and stimulated NO release were measured in the aforementioned groups of rabbits. NO release was measured by using an NO-selective electrode as well as by measuring vascular responses and the plasma NO metabolites nitrite and nitrate. The plasma total cholesterol level was increased, but there were no significant differences in lipid profile in the 4 groups of rabbits that were fed the HCD. The area occupied by atherosclerosis in the thoracic aorta was diminished by approximately 60% in the DHEA-treated rabbits (group 2) compared with the HCD group of rabbits (group 1); there was a corresponding 80% decrease in the estradiol group (group 4) but only a 30% decrease in the DHEA plus fadrozole group (group 3). In the aortas of rabbits from groups 1 and 3, the acetylcholine-induced and tone-related basal NO-mediated relaxations were diminished compared with those of the controls (group 5). However, these relaxations were restored in the aortas of group 2 and 4 rabbits, and an increase in NO release was observed in groups 2 and 4 compared with groups 1 and 3, as measured by an NO-selective electrode. Injection of neither solvent (20% ethanol/distilled water) nor fadrozole significantly affected the atherosclerotic area or the NO-related responses described above. We conclude that approximately 50% of the total antiatherosclerotic effect of DHEA was achieved through the conversion of DHEA to estrogen. NO may also play a role in the antiatherosclerotic effect of DHEA and 17beta-estradiol.
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PMID:Dehydroepiandrosterone retards atherosclerosis formation through its conversion to estrogen: the possible role of nitric oxide. 1071 4

The molecular mechanisms of the antiatherosclerotic effects of estrogen are not yet known. We evaluated the effects of 17beta-estradiol (E(2)) on high cholesterol diet- (HCD; standard diet and 1% cholesterol) and balloon injury-induced atherosclerosis in female New Zealand White rabbits. The abdominal aortas of 40 oophorectomized (Groups 1 through 5) and 8 nonoophorectomized (Group 6) rabbits were injured by balloon catheter, and the animals were then divided into the following groups and treated for 10 weeks: Group 1, standard diet; Group 2, standard diet plus a moderate dose of E(2) (100 microg x kg(-1) x d(-1)); Group 3, HCD; Group 4, HCD plus a moderate dose of E(2); Group 5, HCD plus a low dose of E(2) (20 microg x kg(-1) x d(-1)); and Group 6, HCD in nonoophorectomized rabbits. After the treatment phase, plasma E(2) was increased up to 282.2+/-45.5 pg/mL in Group 2, 263.0+/-41.5 pg/mL in Group 4, 87. 9+/-18.8 pg/mL in Group 5, and 45.6+/-7.3 pg/mL in Group 6. HCD-mediated increases in plasma lipid levels were not changed by E(2) treatment, whereas E(2) decreased the aortic intimal thickening in Group 2 animals compared with those in Group 1 and reduced atherosclerosis in the thoracic and abdominal aortas of Group 4, 5, and 6 rabbits compared with those in Group 3. E(2) restored the impaired abdominal aortic endothelium-dependent relaxation of balloon-injured and HCD-supplemented rabbits, and E(2) increased basal nitric oxide (NO) release. The basal NO-releasing effect showed a significant, inverse relation with the severity of atherosclerosis. Plasma E(2) concentration also showed a significant, inverse relation with atherosclerotic area. In conclusion, physiological concentrations of E(2) can retard the progression of severe atherosclerosis and stabilize atheromas induced by HCD and balloon injury. The retardation may be partially mediated by endothelial NO function in vessels treated with E(2).
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PMID:Physiological concentration of 17beta-estradiol retards the progression of severe atherosclerosis induced by a high-cholesterol diet plus balloon catheter injury: role of NO. 1084 80

Estriol (E3) has little effect on the female genitals. E3 is used in hormone replacement therapy, particularly in Europe and Japan, since it obviates the need for progestin administration. However, the effect of E3 on atherosclerosis has not been elucidated. In this study, we evaluated the effect of E3 on the progression of atherosclerosis in a rabbit model. Thirty-six rabbits total were used. Twenty-eight were bilaterally oophorectomized, and 8 were not. The rabbits were divided into 5 groups and treated for 12 weeks as follows. Gp I (n = 8) was fed a high cholesterol diet (HCD; standard diet plus 0.5% cholesterol); Gp II (n = 8) was fed a HCD with E3 (0.3 mg/kg/day); Gp III (n = 8) was fed a HCD with 17beta estradiol (E2) (0.1 mg/kg/day); Gp IV (n = 8), the non oophorectomized group, was fed a HCD; and Gp NC was oophorectomized (n = 4), and fed a regular diet. E3 treatment increased the plasma E2 and E3 levels in Gp II. The plasma lipid levels were not altered by the E2 or E3 treatment. A HCD diminished the acetylcholine-induced NO mediated relaxation in the thoracic aorta. The E2 treatment (Gp III) and E3 treatment (Gp II) restored the aortic basal NO release and the aortic cyclic GMP levels, particularly effectively in the E3 group. E3 treatment also decreased the atherosclerotic area, and its effect was comparable with E2 (surface involvement: 41.2 +/- 5.1% in Gp I; 10.1 +/- 2.7% in Gp II; and 6.5 +/- 1.3% in Gp III). All four hyperlipidemic groups showed an increase of eNOS mRNA in the aortae, and this was especially pronounced in Gps II and III. The level of peroxynitrite, as determined by immunohistochemical nitrotyrosine staining, was lower in Gps II and III than in Gp I. E3 strongly activates NO-mediated systems, and could play a role in retarding the progression of atherosclerosis and in stabilizing atheroma.
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PMID:Estriol retards and stabilizes atherosclerosis through an NO-mediated system. 1202 Jul 46

Atherosclerosis is a disease of the arteries in which fatty plaques develop on the inner arterial wall, which eventually obstructs blood flow. Identified risk factors for atherosclerosis include genetics, diet, lifestyle, smoking, circulating lipid and cholesterol levels, and molecular and circulating signals of chronic vascular inflammation. The link between flavonoids and atherosclerosis is based partly on the evidence that some flavonoids possess antioxidant properties and have been shown to be potent inhibitors of LDL oxidation in vitro. Hypercholesterolemia, a significant cardiovascular risk factor is prevalent in the American population. Grape seed proanthocyanidin extracts are known to exhibit a broad spectrum of chemopreventive and cardioprotective properties against oxidative stress. A recent study has shown that a combination of IH636 grape seed proanthocyanidin extract (GSPE) and a niacin-bound chromium (NBC) can decrease total cholesterol, LDL and oxidized LDL levels in hypercholesterolemic human subjects. In this study, we assessed the efficacy of GSPE supplementation in hamsters, singly and in combination with NBC, since these animals have a similar lipid profile to hypercholesterolemic humans when fed a hypercholesterolemic diet of 0.2% cholesterol and 10% coconut oil (HCD). After 10 weeks of feeding HCD, these animals developed foam cells, which is a biomarker of early stages of atherosclerosis. Atherosclerosis (% of aorta covered with foam cells) was reduced by approximately 50% and 63% following supplementation of these animals with 50 mg/kg and 100 mg/kg of GSPE, respectively, in conjunction with a HCD, while approximately 32% reduction was observed following supplementation of GSPE plus NBC. A range of 7-9 animals was used in each study group. GSPE alone and in combination with NBC exerted a pronounced effect on the cholesterol, and triglyceride levels, as well as oxidative lipid damage as demonstrated by the formation of thiobarbituric acid reactive substances (TBARS). This data demonstrates that GSPE and NBC may provide significant health benefits by dramatically ameliorating the incidence of atherosclerosis as demonstrated by reducing the formation of foam cells.
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PMID:Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster atherosclerosis model. 1248 76

Although sarpogrelate HCl is widely used for the prevention of arterial thrombosis, its effect on atherosclerosis is unknown. Accordingly, we here investigated the effects of sarpogrelate HCl on a rabbit model of atherosclerosis. Male rabbits were fed a 0.5% cholesterol diet (HCD) (Gp 1), HCD with vitamin E (Gp 2), HCD with vitamin E and sarpogrelate (Gp 3), or HCD with sarpogrelate alone (Gp 4) for 8 weeks. The atherosclerotic area was decreased by feeding of vitamin E and sarpogrelate (16.9+/-2.0% in Gp 1 vs. 8.2+/-2.0% in Gp 3). Tone-related basal NO release was higher in Gps 3 and 4. Acetylcholine-induced relaxation tended to be improved in Gp 3. The amount of eNOS mRNA was increased in Gp 4, and aortic cyclic GMP concentration showed the same tendency. O(2)(-) release tended to be decreased in Gps 2 and 3. The matrix metalloproteinase-1 (MMP-1)-positive area was decreased, and the percentage ratio of cell numbers of smooth muscle cells/macrophages in the plaque was increased in Gp 3. The results demonstrated that sarpogrelate HCl retards the progression of atherosclerosis in rabbits, and that this effect is enhanced by concomitant administration of vitamin E. Although upregulation of eNOS may play a role as one of the underlying mechanisms, our results suggest that an additional mechanism-possibly involving the antiproliferative effects of sarpogrelate HCl on smooth muscle cells and macrophages-may also play an important role.
Atherosclerosis 2003 May
PMID:Sarpogrelate HCl, a selective 5-HT2A antagonist, retards the progression of atherosclerosis through a novel mechanism. 1273 83


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