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

Vascular inflammatory process has been suggested to play a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Lycopus lucidus Turcz. has been used as an oriental traditional medicine including Korea and its crude drug is known to have an anti-inflammatory effect. Thus we investigated whether the aqueous extract of the leaves of L. lucidus Turcz. (ALT) suppresses vascular inflammatory process induced by high glucose in primary cultured human umbilical vein endothelial cells (HUVEC). Western blot analysis revealed that incubation of HUVEC with high glucose increased cell adhesion molecules (CAMs) expression levels. However, high glucose-induced increase of CAMs expression was significantly attenuated by pretreatment with ALT in a dose-dependent manner. The enhanced cell adhesion between monocyte and HUVEC induced by high glucose was also blocked by pretreatment with ALT. High glucose-induced hydrogen peroxide production and DCF-sensitive intracellular reactive oxygen species (ROS) formation. Pretreatment with ALT inhibited high glucose-induced ROS formation. In addition, ALT suppressed the translocation and promoter transcriptional activity of NF-kappaB increased in high glucose condition. Taken together, the present data suggested that ALT could suppress high glucose-induced vascular inflammatory process, which may be closely related with the inhibition of ROS and NF-kappaB activation in HUVEC.
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PMID:Lycopus lucidus inhibits high glucose-induced vascular inflammation in human umbilical vein endothelial cells. 1808 68

Advanced glycation endproducts (AGEs) are unavoidable byproducts of various metabolic pathways. They are formed by reactive metabolic intermediates such as methylglyoxal (MG), glyoxal, and 3-deoxyglucosone. These reactive intermediates bind to proteins, DNA, and other molecules and disrupt their structures and functions, which leads to different diseases such as vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer's disease, and aging. In recent years, more compounds that prevent the formation of AGEs or degrade the existing AGEs have been produced and patented. They include: 1) aminoguanidine, 2) drugs used in the treatment of type 2 diabetes such as metformin and pioglitazone (patented), 3) angiotensin receptor blockers and angiotensin converting enzyme inhibitors, 4) pentoxyfylline (patented), 5) metal ion chelators desferoxamine and penicillamine, 6) antioxidants such as vitamin C or E, 7) amino group capping agents such as aspirin, 8) enzymes that cause deglycation of Amadori products, the Amadoriases, 9) compounds that mostly break alpha-dicarbonyl cross-links such as phenacylthiazolium bromide and its stable derivative ALT-711 (Alagebrium), and 10) derivatives of aryl ureido and aryl carboxaminido phenoxy isobutyric acids (patented). While some of these anti-AGE compounds are being used in clinical practice (such as metformin, pioglitazone, pentoxyfylline and aspirin) or tested in clinical trials (such as aminoguanidine and ALT-711), most of them are commonly used as experimental tools to investigate the role of AGEs in different disease conditions.
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PMID:Methylglyoxal and advanced glycation endproducts: new therapeutic horizons? 1822 Nov 7

Antiretroviral therapy (ART) in HIV-infected patients has been associated with an increased risk of cardiovascular disease. This study evaluates vascular endothelial dysfunction of the peripheral circulation in Brazilian HIV-infected subjects on ART or naive to ART compared to a control group matched for age and body mass index (BMI). We performed a cross-sectional comparative study to measure postischemic peak flow-mediated dilation (FMD) of the brachial artery and the response to glyceryl trinitrate (GTN) in HIV-infected patients and healthy controls in Salvador, Bahia, Brazil. Endothelial vasomotor function was evaluated by assessing brachial artery FMD. Forty-four HIV-infected individuals (33 ARV treated and 11 ART naive) were compared to 25 healthy controls matched for age and BMI. FMD % was significantly lower for the ART-experienced patients compared to the ART-naive patients and was also significantly different from controls (ART experienced 8.2 +/- 6.0% vs. 19.3 +/- 4.8% vs. 23.3 +/- 6.1%), respectively (p < 0.0001). The cholesterol, triglyceride, and ALT levels were significantly higher in the ART-experienced group compared to the ART-naive and control subjects (p < 0.028); however, linear regression analysis revealed a statistically significant association of endothelial dysfunction as a dependent variable only with ARV treatment in HIV-infected subjects (p = 0.03). The association of endothelial dysfunction with ARV therapy in HIV-infected patients was independent of protease inhibitor-containing regimens or dyslipidemia. This dysfunction may contribute to the risk for HIV-associated atherosclerosis.
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PMID:Cross-sectional study of endothelial function in HIV-infected patients in Brazil. 1827 45

1. The worldwide epidemic of obesity in adults has been mirrored in children in developed and developing countries. 2. Central obesity appears to be driving a cluster of abnormalities often referred to as the metabolic syndrome. 3. The definition of the metabolic syndrome in children is not suited to arbitrary cut-offs and a definition using the significant clustering of risk factors that is already evident in childhood and adolescent populations may be preferable. 4. An Australian population study showed that 25% of 8-year-olds and 29% of 14-year-olds could be described by the high risk cluster with features similar to adult metabolic syndrome. 5. The high risk cluster was significantly linked to high and low birthweight, shorter duration of breast-feeding, larger postnatal weight gains after 12 months of age and raised C-reactive protein, gamma glutamyl transferase and alanine transaminase levels. At-risk young adults have also been shown to have macroscopic atherosclerosis in post-mortem studies. 6. Identification of at-risk children has obvious benefits for the individual and as well, for prevention of a future cohort with raised cardiovascular morbidity and mortality; however, complexities and controversies exist in doing so. Familial, genetic and lifestyle risk factors aggregate and labelling children with predisease may be problematic. Committed political and societal changes are necessary to reduce childhood obesity and subsequent adult cardiovascular disease.
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PMID:Childhood obesity, hypertension, the metabolic syndrome and adult cardiovascular disease. 1830 30

Recent studies have raised questions about the long-term health risks for individuals with mutations in the HFE gene, although previous studies may have been plagued by selection bias or lack of population-based comparison groups. We examined cardiovascular disease risk factors and iron and liver biomarkers, as well as morbidity and mortality associated with the C282Y and H63D variants of HFE in the Atherosclerosis Risk in Communities (ARIC) study, which is a population-based cohort of nearly 16,000 U.S. white and black men and women who were 45-64 years old at baseline. Subjects were followed for an average of 15 years for death, incident coronary heart disease, stroke, and heart failure, and an average of 8 years for incident diabetes. The prevalence of C282Y homozygosity was 0.42% (45/10,800) in whites, which is similar to other North American population-based studies. C282Y homozygotes had significantly lower mean low-density lipoprotein (LDL) cholesterol and fibrinogen as well as higher mean levels of iron (ferritin, transferrin saturation) and liver biomarkers (alanine aminotransferase, Hepascore) compared with HFE wild-type subjects. Rates of all-cause mortality, cardiovascular disease, and diabetes were similar across HFE genotypes. These prospective, population-based data indicate higher serum iron indices and possible mild liver dysfunction or disease in some C282Y homozygotes, but they provide little evidence that HFE C282Y or H63D mutations are related to all-cause mortality, cardiovascular disease, or diabetes. Reduced LDL in C282Y homozygotes may be because of effects of excess iron on cholesterol metabolism and lipoprotein formation in the liver.
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PMID:HFE C282Y homozygotes have reduced low-density lipoprotein cholesterol: the Atherosclerosis Risk in Communities (ARIC) Study. 1859 31

Lysosomal acid lipase (LAL) deficiency results in Wolman disease and cholesteryl ester storage disease (CESD), a more benign form. CESD is a recessive disorder characterized by hypercholesterolaemia, hypertriglyceridaemia, low blood HDL and variable phenotype, while hepatomegaly is usually evident during childhood or adolescence. An 11-year-old girl was referred to our department for combined hyperlipidaemia (total cholesterol 323, triglycerides 259 mg/dl). All family members had normal lipid profile and liver function tests. At 8 years she was admitted for acute Epstein-Barr virus infection, with hepatosplenomegaly and elevation of liver enzymes. Liver-spleen enlargement resolved, but serum alanine aminotransferase and aspartate aminotransferase were persistently twice the upper limits, with other liver function tests within the normal range. Ultrasonography showed normal liver and spleen size and minimal hepatic steatosis. Infectious, autoimmune and metabolic causes of elevated liver enzymes were ruled out, including glycogen storage disease. Dysbetalipoproteinaemia was also ruled out (ApoE phenotype: E3E3). In the following 2 years the girl was symptom-free, BMI was at the 50th-75th centile for age and lipid profile was unchanged despite a low-fat diet. At 13 years of age, low acid lipase activity was demonstrated in leukocytes (10 nmol/h/ per mg protein, normal 140-380) and cultured skin fibroblasts (181 nmol/h per mg protein, normal 1100-2400), leading to diagnosis of CESD. CESD usually progresses to hepatic fibrosis, with high risk of premature atherosclerosis. CESD prevalence may be underestimated in the general population. The diagnosis may be considered in all subjects with atypical combined hyperlipidaemia (usually dominant in transmission or related to metabolic syndrome) and atypical 'fatty liver disease', in the absence of overweight.
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PMID:Combined hyperlipidaemia as a presenting sign of cholesteryl ester storage disease. 1921 73

Advanced glycation end product receptor (RAGE) interaction plays an important role in atherosclerosis. Although exogenously administered soluble form of RAGE (sRAGE) has been shown to suppress the development and progression of atherosclerosis in animals, the kinetics and role of endogenous sRAGE in humans are not fully understood. In this study, to clarify whether endogenous sRAGE could capture and efficiently eliminate RAGE ligands such as circulating AGEs and high-mobility group box-1 (HMGB-1), we investigated the correlation between sRAGE and RAGE ligands and examined independent determinants of serum levels of sRAGE in hypertensive humans. Two-hundred seventy-one consecutive nondiabetic outpatients with essential hypertension (83 male and 188 female; mean age, 76.5 +/- 9.2 years) underwent a complete history, physical examination, and determination of blood chemistries, including serum levels of sRAGE, AGEs, and HMGB-1. Univariate regression analysis showed that serum levels of sRAGE were associated with body mass index (r = -0.313, P < .0001), waist (r = -0.214, P < .0001), alanine aminotransferase (r = -0.172, P = .005), gamma-glutamyltranspeptidase (r = -0.213, P < .0001), 24-hour creatinine clearance (r = -0.348, P < .0001), B-type natriuretic peptide (r = 0.138, P = .027), tumor necrosis factor-alpha (r = 0.138, P = .002), and alcohol intake (r = -0.155, P = .010). By the use of multiple stepwise regression analyses, 24-hour creatinine clearance (P < .0001), gamma-glutamyltranspeptidase (P < .001), body mass index (P = .007), and tumor necrosis factor-alpha (P = .024) remained significant independently. The present study demonstrated for the first time that there was no significant correlation between serum levels of sRAGE and RAGE ligands such as circulating AGEs and HMGB-1 in hypertensive patients. Anthropometric and inflammatory variables and liver and renal function may be the determinants of endogenous sRAGE levels in nondiabetic hypertensive patients.
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PMID:Independent determinants of soluble form of receptor for advanced glycation end products in elderly hypertensive patients. 1921 61

It is documented that hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis, but whether elevated plasma homocysteine contributes to the progression of atherosclerosis in aged animals with hypercholesterolemia is still unknown. HHcy was induced in apolipoprotein E (ApoE) knockout mice (male, 32 weeks old) by feeding 2% methionine/low folate (1 mg/kg) diet for 20 weeks. HHcy induced by methionine feeding significantly increased oxidative stress, as measured by thiobarbituric-reactive substances in livers (P < .05) and genetic expression of Cu,Zn-superoxide dismutase, in methionine-fed animals compared with controls (P < .05). Furthermore, lipoprotein profiles were changed, in that low-density lipoprotein-cholesterol was shifted to very low-density lipoprotein in the methionine-supplemented group. However, nuclear factor kappaB activity, atherosclerotic lesions, hepatic glutathione level, lipid profiles, and activities of aspartate aminotransferase and alanine aminotransferase were not significantly different. These findings suggest that HHcy induced by methionine may promote disturbances in lipid peroxidation and modify lipoprotein metabolism but not contribute to the progression of atherosclerotic lesion in aged ApoE knockout mice.
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PMID:Methionine-induced hyperhomocysteinemia modulates lipoprotein profile and oxidative stress but not progression of atherosclerosis in aged apolipoprotein E knockout mice. 1929 7

Data on the utility of the waist-to-height ratio in detecting central obesity and related cardiovascular risk among normal weight younger adults are scant. This aspect was examined in 639 normal weight (body mass index 18.5 to 24.9 kg/m(2)) black and white adults (75% white and 36% men) 20 to 44 years old. The subjects with a waist-to-height ratio > or =0.5 were grouped as having central obesity normal weight, with the rest considered the control group. The subjects with central obesity, compared to the controls, after adjusting for age, race, and gender, had significantly greater diastolic blood pressure, mean arterial pressure, low-density lipoprotein cholesterol level, triglycerides, triglycerides/high-density lipoprotein cholesterol ratio, insulin, homeostasis model assessment of insulin resistance, uric acid, C-reactive protein, and liver function enzymes (alanine aminotransferase and gamma-glutamyl transferase). On multivariate analysis, the central obesity group compared to the control group was 1.9, 2.2, 2.9, and 2.5 times more likely to have significantly adverse levels (top tertile vs the rest) of mean arterial pressure, triglycerides/high-density lipoprotein cholesterol ratio, homeostasis model assessment of insulin resistance, and C-reactive protein, respectively. The central obesity group also had a greater prevalence of dyslipidemia, hypertension, insulin resistance, hyperuricemia, and elevated C-reactive protein. The age-, race-, and gender-adjusted mean value of the common carotid intima-media thickness, a measure of subclinical atherosclerosis, was greater in the central obesity group compared to the control group (0.76 vs 0.71 mm, p = 0.009). In conclusion, these findings underscore the utility of the waist-to-height ratio in detecting central obesity and related adverse cardiovascular risk among normal weight younger adults.
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PMID:Utility of waist-to-height ratio in detecting central obesity and related adverse cardiovascular risk profile among normal weight younger adults (from the Bogalusa Heart Study). 1969 51

Cholesterol and sphingolipids are major lipid constituents of the plasma membrane and have been implicated in a number of human diseases, such as atherosclerosis, fatty liver, diabetes mellitus, coronary heart disease, and hypertension. However, the relationship between cholesterol and sphingolipid metabolism has not been investigated. The purpose of this study was to determine whether dietary cholesterol would induce the alteration of sphingolipid metabolism in hamsters. Hypercholesterolemia was induced in hamsters by placing them on an experimental diet containing 0.5% cholesterol plus 0.5% choline chloride for 8 and 12 weeks. The serum profile of the hamsters showed that the administration of cholesterol increased the levels of total cholesterol, LDL cholesterol, and triglycerides as well as the activities of GOT and GPT. The levels of ceramide and sphingosine-1-phosphate (So-1-P) were remarkably elevated by 6-fold, respectively, in the bile juice of cholesterol-fed hamsters. Interestingly, the levels of iNOS and GFAP were increased in the gallbladders of cholesterol-fed hamsters. In addition, the immunostaining of pSTAT3 was increased on the gallbladder epithelium after cholesterol feeding. These results suggest that sphingolipid metabolism may be regulated in the bile juice during cholesterol feeding and may be a potential target for the treatment of hypercholesterolemia-induced diseases.
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PMID:Alteration of sphingolipid metabolism and pSTAT3 expression by dietary cholesterol in the gallbladder of hamsters. 1978 70


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