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

While the hypocholesterolemic effects of taurine have extensively been studied using experimental animals, the anti-atherosclerotic effects of taurine have been given less attention. We examined the effect of taurine on atherosclerotic lesions in Watanabe heritable hyperlipidemic (WHHL) rabbits. Treatment of WHHL rabbits with taurine (0.3% in drinking tap water) for 24 weeks decreased aortic lesions by 31%, estimated as intimal thickening. Taurine significantly decreased cholesteryl ester content of aortic arch, thoracic aorta, and abdominal aorta by 35, 43, and 54%, respectively. Concomitantly, activity of acyl-CoA:cholesterol acyltransferase (ACAT), an enzyme responsible for cholesterol esterification, was also significantly decreased. Immunohistochemical analysis revealed decreased macrophages in the intima of taurine-treated rabbits. Taurine had no apparent effect on blood pressure and serum cholesterol levels. Contents of thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, was reduced in serum and aorta by 29 and 50%, respectively, when taurine was ingested. In addition, LDL from taurine-treated rabbits was resistant to copper-induced oxidative modification. These results revealed that taurine prevents development of atherosclerosis and that the anti-atherosclerotic effects of taurine are independent of serum cholesterol levels. The anti-oxidant action of taurine may be involved in inhibiting atherosclerosis in these rabbits.
Atherosclerosis 2002 Jul
PMID:Taurine suppresses development of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. 1204 24

The arsenic-related peripheral vascular disease found to be endemic along the southwestern coast of Taiwan is reviewed. In the early 20th century a strange disease involving the lower extremities characterized by typical clinical symptoms and signs of progressive arterial occlusion was reported in a confined area located along the southwestern coast of Taiwan. The disease was locally called "blackfoot disease" because of its gangrenous appearance involving the feet of the patients. The prevalence of this disease ranged from 6.51 to 18.85 per 1,000 population in different villages. Epidemiologic studies revealed that blackfoot disease was associated with the consumption of artesian well water containing high levels of arsenic. High co-occurrence of blackfoot disease and arsenic-related skin lesions such as hyperpigmentation, hyperkeratosis, and skin cancer was also observed. Recent studies also confirmed the association of preclinical peripheral vascular disease with arsenic exposure in a dose-response pattern. Subclinical arterial insufficiency and defects in cutaneous microcirculation can also be demonstrated in seemingly normal subjects living in the endemic villages. The incidence of clinical manifestation of blackfoot disease decreased dramatically after the implementation of tap water in these villages over the past 2-3 decades. The atherogenicity of arsenic could be associated with its effects on hypercoagulability, endothelial injury, smooth muscle cell proliferation, somatic mutation, oxidative stress, and apoptosis. However, its interaction with some trace elements and its association with hypertension and diabetes mellitus could also explain part of its higher risk of developing atherosclerosis.
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PMID:An overview on peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan. 1236 59

This study was performed to investigate whether the plasma concentration of phosphatidylcholine hydroperoxide (PCOOH), which is a marker of oxidized stress in the blood, increased in cholesterol-fed rabbits, and fructose ingestion promoted this process and aggravated atherosclerosis. Male Japanese white rabbits (age: 12 weeks, and body weight: around 2.0 kg, n = 15) were divided into three groups, (1) a NN group as a normal control fed a standard diet (n = 5), (2) a CN group fed 1.0% cholesterol, and (3) a CF group given both 1.0% cholesterol and 10% fructose-containing tap water. During 8 weeks, plasma PCOOH levels increased significantly in the CN and CF groups compared to the NN group and fructose further raised the PCOOH level. The atherosclerosis was significantly promoted and the deposition of advanced glycation end products (AGEs) was marked in the CF group compared to the CN group. Fructose worsened the atheromatous lesions caused by cholesterol feeding. The mechanism is most likely through lipid peroxidation, which was increased by cholesterol feeding-induced hyperlipidemia, and the formation of AGEs.
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PMID:Fructose ingestion enhances atherosclerosis and deposition of advanced glycated end-products in cholesterol-fed rabbits. 1620 22

Blackfoot disease (BFD) is an endemic peripheral vascular disease confined to the southwestern coast of Taiwan. This article reviews the epidemiology, clinical manifestations and diagnosis, pathology, etiology and pathogenesis of this disease. Sporadic cases of BFD occurred as early as in the early 20th century, and peak incidence was noted between 1956 and 1960, with prevalence rates ranging from 6.51 to 18.85 per 1,000 population in different villages. Typical clinical symptoms and signs of progressive arterial occlusion mainly found in the lower extremities, but in rare cases, the upper extremities might also be involved. Ulceration, gangrene and spontaneous or surgical amputation were typical fate. An extensive pathological study concluded that 30% of the BFD patients had histologic lesions compatible with thromboangiitis obliterans and 70% showed changes of arteriosclerosis obliterans. Epidemiologic studies carried out since mid-20th century revealed that BFD was associated with the consumption of inorganic arsenic from the artesian wells. Recent studies confirmed the existence of preclinical peripheral vascular disease, subclinical arterial insufficiency and defects in cutaneous microcirculation in the residents of the endemic villages. A more recent study suggested that the methylation capacity of arsenic can interact with arsenic exposure in the development of peripheral vascular disease among residents of BFD-endemic areas. The incidence of BFD decreased dramatically after the implementation of tap water in these villages over the past 2-3 decades. The atherogenicity of arsenic could be associated with its effects of hypercoagulability, endothelial injury, smooth muscle cell proliferation, somatic mutation, oxidative stress, and apoptosis. However, its interaction with some trace elements and its association with hypertension and diabetes mellitus could also explain part of its higher risk of developing atherosclerosis. Although humic substances have also been suggested as a possible cause of BFD, epidemiologic studies are required to confirm its etiologic role.
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PMID:Blackfoot disease and arsenic: a never-ending story. 1629 22

1. Hypothyroidism is accompanied by hyperlipidaemia and oxidative stress and is associated with several complications, such as atherosclerosis. Paraoxonase activity has been reported to decrease in several situations associated with atherosclerosis and oxidative stress. In the present study, the effects of different doses of taurine on serum paraoxonase and arylesterase activities, as well as on the serum lipid profile, were investigated in hypothyroid rats. 2. Forty male Sprague-Dawley rats were randomly divided into five groups as follows: Group 1, rats received normal rat chow and tap water; Group 2, rats received standard rat chow + 0.05% propylthiouracil (PTU) in the drinking water; and Groups 3-5, taurine-supplemented PTU groups (standard rat chow + 0.5, 2 or 3% taurine in the drinking water, respectively, in addition to PTU). Paraoxon or phenylacetate were used as substrates to measure paraoxonase and arylesterase activity, respectively. Plasma and tissue malondialdehyde (MDA) levels, indicators of lipid peroxidation, were determined using the thiobarbituric-acid reactive substances method. Serum triglyceride, total cholesterol and high-density lipoprotein-cholesterol (following precipitation with dextran sulphate-magnesium chloride) were determined using enzymatic methods. 3. Serum paraoxonase and arylesterase activities were increased and plasma and tissue MDA levels and serum triglyceride levels were reduced in a dose-dependent manner in taurine-treated hypothyroid rats. Taurine concentrations were positively correlated with enzyme activities and negatively correlated with MDA and triglyceride levels. 4. Further studies are needed to investigate the role of taurine supplementation in hypothyroidism in human subjects.
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PMID:High-dose taurine supplementation increases serum paraoxonase and arylesterase activities in experimental hypothyroidism. 1764 25

Since lipid oxidation is involved in the deterioration of hypercholesterolemia-related atherosclerosis, ingestion of drinks and foods with antioxidant actions is useful for preventing lipid oxidation. Goishi-tea is a post-fermented-tea manufactured by a unique method in Japan, and may be useful for preventing various disorders. However, there is no scientific evidence. In this study, we compared the radical scavenging activity of goishi-tea with that of other teas, and administered this tea to a rabbit model of hypercholesteremia to evaluate its usefulness in the inhibition of hypercholesteremia and atherosclerosis. The radical scavenging activity of goishi-tea was similar to that of green-tea, and was higher than that of other types of fermented-teas. On the other hand, some difference of components was found between goishi-tea and green-tea. In cholesterol-fed rabbits, low-density lipoprotein (LDL)-cholesterol level in the goishi-tea-group was lower than that in the green-tea-group. Plasma lipidperoxide value was also lower in the goishi-tea-group than in the green-tea and tap-water-groups. On aortic endothelial staining, fat area in the goishi-tea-group was lower than that in the tap-water-group. Furthermore, fat accumulation in the aortic intima in the goishi-tea-group was very low. Goishi-tea has higher antioxidant activities than the other fermented-teas tested, which were generally low, and decreased serum lipid levels, suggesting that goishitea is a very peculiar fermented-tea with usefulness in the prevention of hypercholesterolemia and atherosclerosis.
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PMID:[Inhibitory effects of "Goishi-tea" as a post-fermented-tea on dietary-induced hypercholesteremia and atherosclerosis in rabbits]. 1859 72

Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD), but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT, GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects, arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure >14.7 ppm-year or drinking artesian well water >21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful biomarker of arsenic risk.
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PMID:Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality. 1915 5

The effects of taurine supplementation on the serum cholesterol levels and the progression of atherosclerosis were investigated in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail. The ingestion of a high-cholesterol diet containing 1% cholesterol by LAP quails for 60 days resulted in a marked elevation in serum non-HDL cholesterol and triglyceride, as well as severe aortic lesions with lipid droplets. An immunohistochemical study showed that the lesion consisted of mainly lipid-rich macrophages and T cells. Sixty-day taurine supplementation (1% in drinking tap water) to LAP quails fed high-cholesterol diet containing 1% cholesterol significantly reduced serum non-HDL cholesterol from 4,549 to 2,350 mg/dl. The serum triglyceride level also decreased after taurine supplementation from 703 to 392 mg/dl. Although the HDL cholesterol level significantly decreased due to the high-cholesterol diet, it recovered to the control level fed a regular diet in response to taurine. Bile acid production was stimulated and hepatic cholesterol was reduced by taurine supplementation. A quantitative analysis using aortic cross-sections showed that areas of oil-red O positive lipid accumulation significantly decreased by 74% after taurine supplementation. These results demonstrated the lipid-lowering and anti-atherosclerotic effects of taurine in a diet-induced hyperlipidemic LAP quail model. The prevention of atherosclerosis by taurine is mainly attributed to an improvement in the serum cholesterol and triglyceride levels, which may be related to changes in the hepatic cholesterol metabolism.
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PMID:Prevention of hypercholesterolemia and atherosclerosis in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail by taurine supplementation. 1922 88

Rho kinases have been shown to be involved in the pathogenesis of atherosclerosis. This study examined the effects of fasudil, a specific Rho kinase inhibitor, on plaque development and progression in atherosclerotic mice. Sixty apolipoprotein E-knockout (apoE-KO) mice were fed a high-fat diet. Mice started to receive fasudil at the same time as fat feeding (early treatment), or after 12 weeks of fat feeding (delayed treatment). In each administrative schedule, mice were divided into three groups: low dose fasudil group (30 mg/kg/day), high dose fasudil group (100mg/kg/day) and control group (tap water) (n=10, respectively). Plaque size was determined by using ultrasound biomicroscopy (UBM) and histological examinations. Brachiocephalic artery UBM analysis showed that in early treatment, both doses of fasudil significantly reduced lesion size compared with the controls (P<0.05). In delayed-fasudil treatment, plaque area was reduced by 54% (P<0.05) after 12 weeks of treatment at a high dose of fasudil (100mg/kg/day). The UBM findings were confirmed by histological studies at the corresponding arterial sites. The beneficial effect was also observed in the left common carotid arteries that delayed-fasudil treatment reduced the plaque size in a dose-dependent manner. The arterial intima-medial thickness (IMT) and maximal flow velocity of both arteries were lower in fasudil-treated group (100mg/kg/day) in comparison with the control mice. Furthermore, fasudil treatment (100mg/kg/day) reduced the macrophage accumulation in atherosclerotic lesions. However, fasudil had no effects on blood pressure and plasma lipid concentrations in both studies. In conclusion, our studies showed that blocking Rho kinase reduced both the early development and later progression of atherosclerotic plaques in apoE-KO mice by using a novel micro-ultrasound approach.
Atherosclerosis 2009 Nov
PMID:Effects of fasudil on early atherosclerotic plaque formation and established lesion progression in apolipoprotein E-knockout mice. 1947 57

1. Regulation of vascular Nox2-containing NADPH oxidase by p47(phox) plays a pivotal role in the development of atherosclerotic lesions through the generation of superoxide. Reduced vascular nitric oxide (NO) bioavailability is a major contributing factor in the initiation of atherosclerosis because it leads to an increase in adhesion molecule expression for inflammatory cell recruitment into the vessel wall. 2. The aim of the present study was to examine whether the anti-oxidant and anti-inflammatory effects of endogenous NO involve inhibition of NADPH oxidase-dependent superoxide production. 3. To inhibit endogenous NO production, male C57Bl/6 wild-type (WT) mice or age-matched p47(phox-/-) mice were treated with N(G)-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg per day for 4 weeks). Blood pressure was measured weekly via the tail-cuff method. Basal and phorbol dibutyrate (PDB)-stimulated aortic superoxide production was detected using lucigenin- and L-012-enhanced chemiluminescence, respectively. Aortic Nox2, p47(phox) and vascular cell adhesion molecule (VCAM)-1 expression were measured with western blotting. Plasma angiotensin (Ang) II levels were determined by radioimmunoassay. 4. Compared with vehicle (tap water)-treated WT mice (n = 4), L-NAME-treated WT mice had significantly higher systolic blood pressure (SBP; n = 6; P < 0.05) and basal and stimulated aortic extracellular superoxide production (n = 6-8; P < 0.05), but lower plasma AngII levels (P < 0.05). There was no change in Nox2 expression following l-NAME treatment of WT mice (n = 6); however, significant increases in both aortic p47(phox) (n = 6; P < 0.05) and VCAM-1 expression (n = 6; P < 0.05) were observed. In p47(phox-/-) mice, l-NAME treatment significantly increased SBP (n = 3-4; P < 0.05), but failed to increase aortic superoxide production and VCAM-1 expression. 5. In conclusion, endogenous NO suppresses vascular inflammation, via inhibition of p47(phox) expression, leading to attenuation of NADPH oxidase-dependent superoxide production.
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PMID:Evidence that nitric oxide inhibits vascular inflammation and superoxide production via a p47phox-dependent mechanism in mice. 1984 95


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