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Jae Hak Park - One of the best experts on this subject based on the ideXlab platform.

John P Cooke - One of the best experts on this subject based on the ideXlab platform.

  • angiogenesis is impaired by Hypercholesterolemia role of asymmetric dimethylarginine
    Circulation, 2000
    Co-Authors: James J Jang, Helen H Kwan, Luis F Fajardo, Hoai Ky V Ho, John P Cooke
    Abstract:

    Background—Many angiogenic factors require endothelium-derived nitric oxide (NO) to exert their effects. Recently, an endogenous competitive antagonist of NO synthase has been characterized: asymmetric dimethylarginine (ADMA). Elevated plasma levels of ADMA reduce NO synthesis in Hypercholesterolemia. Accordingly, we hypothesized that Hypercholesterolemia impairs angiogenesis by an ADMA-dependent mechanism. Methods and Results—Angiogenesis was assessed with the use of a disk angiogenesis system implanted subcutaneously in normal (E+) mice or apolipoprotein (apo)E-deficient hypercholesterolemic (E−) mice. After 2 weeks, the disks were removed, and the fibrovascular growth area was used as an index of angiogenesis. Basal and fibroblast growth factor–stimulated angiogenesis was impaired in E− mice, associated with an elevation in plasma ADMA. Oral administration of l-arginine reversed the impairment of angiogenesis in E− mice. By contrast, oral administration of l-nitroarginine (an exogenous antagonist of NO...

  • asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans
    Arteriosclerosis Thrombosis and Vascular Biology, 2000
    Co-Authors: Jason R Chan, Rainer H Boger, Stefanie M Bodeboger, Oranee Tangphao, Philip S Tsao, Terrence F Blaschke, John P Cooke
    Abstract:

    Abstract —Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is elevated in Hypercholesterolemia. This study was designed to determine the role of ADMA in the increased mononuclear cell adhesiveness observed in human Hypercholesterolemia. In patient studies, plasma ADMA levels were determined by high-performance liquid chromatography. Functional mononuclear leukocyte adhesion assays were performed in parallel, and flow cytometry was used to characterize bound monocytes and T lymphocytes. Hypercholesterolemic patients were then placed on an oral l-arginine regimen of 14 or 21 g/d and studied over 12 weeks. In cell culture studies, bovine aortic endothelial cells were incubated with varied concentrations of ADMA. Monocytoid cells were cocultured with these bovine aortic endothelial cells, and their adhesiveness was assessed by use of a binding assay. Flow cytometry was used to quantify adhesion molecule expression. Plasma ADMA levels and adhesiveness of mononuclear cells (specifically, monocytes and T lymphocytes) were elevated in hypercholesterolemic patients. Adhesiveness was inversely correlated with the plasma l-arginine/ADMA ratio. Oral administration of l-arginine normalized plasma l-arginine/ADMA ratios and attenuated monocyte and T-lymphocyte adhesiveness. ADMA had no direct effect on the adhesiveness of mononuclear cells. However, monocytes became hyperadhesive when cocultured with ADMA-exposed endothelial cells. In human Hypercholesterolemia, the plasma l-arginine/ADMA ratio is inversely correlated with mononuclear cell adhesiveness. Restoration of the l-arginine/ADMA ratio to control levels normalizes mononuclear cell adhesiveness. Our studies suggest that the elaboration of endothelium-derived nitric oxide affects the behavior of circulating T lymphocytes and monocytes.

  • asymmetric dimethylarginine adma a novel risk factor for endothelial dysfunction its role in Hypercholesterolemia
    Circulation, 1998
    Co-Authors: Rainer H Boger, Jason R Chan, Stefanie M Bodeboger, Oranee Tangphao, Philip S Tsao, Terrence F Blaschke, Andrzej Szuba, John P Cooke
    Abstract:

    Background—Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. Because endothelial NO elaboration is impaired in Hypercholesterolemia, we investigated whether plasma concentrations of ADMA are elevated in young, clinically asymptomatic hypercholesterolemic adults. We further studied whether such elevation of ADMA levels was correlated with impaired endothelium-dependent, NO-mediated vasodilation and urinary nitrate excretion. In a randomized, double-blind, placebo-controlled study, we investigated whether these changes could be reversed with exogenous l-arginine. Methods and Results—We measured plasma levels of l-arginine, ADMA, and symmetrical dimethylarginine (SDMA) by high-performance liquid chromatography in 49 hypercholesterolemic (HC) and 31 normocholesterolemic (NC) humans. In 8 HC subjects, endothelium-dependent forearm vasodilation was assessed before and after an intravenous infusion of l-arginine or placebo and compared with 8 NC control subj...

  • l arginine improves endothelium dependent vasodilation in hypercholesterolemic humans
    Journal of Clinical Investigation, 1992
    Co-Authors: Mark A Creager, Shelly J Gallagher, X Girerd, Sharon M Coleman, Victor J Dzau, John P Cooke
    Abstract:

    Endothelium-dependent vasodilation is impaired in Hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with Hypercholesterolemia (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hypercholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor.

Pitchairaj Geraldine - One of the best experts on this subject based on the ideXlab platform.

  • antihypercholesterolemic and antioxidative potential of an extract of the plant piper betle and its active constituent eugenol in triton wr 1339 induced Hypercholesterolemia in experimental rats
    Evidence-based Complementary and Alternative Medicine, 2014
    Co-Authors: Karuppasamy Venkadeswaran, Arumugam Ramachandran Muralidharan, Thangaraj Annadurai, Vasanthakumar Vasantha Ruban, Mahalingam Sundararajan, Ramalingam Anandhi, Philip A Thomas, Pitchairaj Geraldine
    Abstract:

    Hypercholesterolemia is a dominant risk factor for atherosclerosis and cardiovascular diseases. In the present study, the putative antihypercholesterolemic and antioxidative properties of an ethanolic extract of Piper betle and of its active constituent, eugenol, were evaluated in experimental Hypercholesterolemia induced by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg b.wt) in Wistar rats. Saline-treated hypercholesterolemic rats revealed significantly higher mean blood/serum levels of glucose, total cholesterol, triglycerides, low density and very low density lipoprotein cholesterol, and of serum hepatic marker enzymes; in addition, significantly lower mean serum levels of high density lipoprotein cholesterol and significantly lower mean activities of enzymatic antioxidants and nonenzymatic antioxidants were noted in hepatic tissue samples from saline-treated hypercholesterolemic rats, compared to controls. However, in hypercholesterolemic rats receiving the Piper betle extract (500 mg/kg b.wt) or eugenol (5 mg/kg b.wt) for seven days orally, all these parameters were significantly better than those in saline-treated hypercholesterolemic rats. The Hypercholesterolemia-ameliorating effect was better defined in eugenol-treated than in Piper betle extract-treated rats, being as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt). These results suggest that eugenol, an active constituent of the Piper betle extract, possesses antihypercholesterolemic and other activities in experimental hypercholesterolemic Wistar rats.

  • antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom pleurotus ostreatus and its major constituent chrysin in triton wr 1339 induced hypercholesterolemic rats
    Journal of Physiology and Biochemistry, 2013
    Co-Authors: Ramalingam Anandhi, Arumugam Ramachandran Muralidharan, Thangaraj Annadurai, Philip A Thomas, Thirugnanasambandhar Sivasubramanian Anitha, Kalifulla Najmunnisha, Vasanthi Nachiappan, Pitchairaj Geraldine
    Abstract:

    Hypercholesterolemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. In the present study, an attempt was made to evaluate the putative antihypercholesterolemic and antioxidative effects of an ethanolic extract of the oyster mushroom (Pleurotus ostreatus) and chrysin, one of its major components, in hypercholesterolemic rats. Hypercholesterolemia was induced in rats by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg body weight (b.wt.)), which resulted in persistently elevated blood/serum levels of glucose, lipid profile parameters (total cholesterol, triglycerides, low-density lipoprotein-, and very low-density lipoprotein-cholesterol), and of hepatic marker enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase). In addition, lowered mean activities of hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) and lowered mean levels of nonenzymatic antioxidants (reduced glutathione, vitamin C, and vitamin E) were observed. Oral administration of the mushroom extract (500 mg/kg b.wt.) and chrysin (200 mg/kg b.wt.) to hypercholesterolemic rats for 7 days resulted in a significant decrease in mean blood/serum levels of glucose, lipid profile parameters, and hepatic marker enzymes and a concomitant increase in enzymatic and nonenzymatic antioxidant parameters. The Hypercholesterolemia-ameliorating effect was more pronounced in chrysin-treated rats than in extract-treated rats, being almost as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt.). These results suggest that chrysin, a major component of the oyster mushroom extract, may protect against the Hypercholesterolemia and elevated serum hepatic marker enzyme levels induced in rats injected with Triton WR-1339.

Seung Hyeok Seok - One of the best experts on this subject based on the ideXlab platform.

Wulf Palinski - One of the best experts on this subject based on the ideXlab platform.

  • maternal c reactive protein and developmental programming of atherosclerosis
    American Journal of Obstetrics and Gynecology, 2008
    Co-Authors: Francesco P Darmiento, Antonio Palagiano, Wulf Palinski, Claudio Napoli
    Abstract:

    OBJECTIVE: Maternal Hypercholesterolemia during pregnancy enhances the susceptibility to atherosclerosis in their offspring by oxidation-dependent mechanisms. The present study investigated whether maternal C-reactive protein (CRP) level, which is an indicator of inflammation and cardiovascular risk, or smoking, which enhances oxidative stress, predict the in utero programming of atherosclerosis. STUDY DESIGN: Subsets of patients from the Fate of Early Lesions in Childhood study (156 normocholesterolemic children) were examined at autopsy, classified by maternal cholesterol levels during pregnancy. Maternal CRP level was correlated with maternal cholesterol and aortic atherosclerosis of children. RESULTS: CRP level was elevated in hypercholesterolemic mothers and showed significant correlation with atherogenesis in children in univariate and multivariate analysis. However, many hypercholesterolemic mothers did not have elevated CRP levels. Smoking only correlated in univariate analysis. CONCLUSION: CRP level during pregnancy is a predictor of increased atherogenesis in children of hypercholesterolemic mothers, albeit a weaker one than maternal cholesterol. In the presence of Hypercholesterolemia, maternal smoking does not further enhance atherogenic programming.

  • maternal Hypercholesterolemia and treatment during pregnancy influence the long term progression of atherosclerosis in offspring of rabbits
    Circulation Research, 2001
    Co-Authors: Wulf Palinski, Francesco P Darmiento, Filomena De Nigris, Joseph L Witztum, Florencia Casanada, M Condorelli, Mercedes Silvestre, Claudio Napoli
    Abstract:

    Maternal Hypercholesterolemia during pregnancy is associated with enhanced fatty streak formation in human fetuses and faster progression of atherosclerosis during childhood even under normocholesterolemic conditions. A causal role of maternal Hypercholesterolemia in lesion formation during fetal development has previously been established in rabbits. The same experimental model is now used to establish that maternal Hypercholesterolemia or ensuing pathogenic events in fetal arteries enhance atherogenesis later in life. Five groups of rabbit mothers were fed chow, cholesterol-enriched chow, or cholesterol-enriched chow plus 1000 IU vitamin E, 3% cholestyramine, or both during pregnancy. Offspring of all groups (n=136) were fed a mildly hypercholesterolemic diet for up to a year and had similar cholesterol levels. Aortic lesion sizes and lipid peroxidation products in plasma and lesions in offspring were determined at birth, 6 months, or 12 months. Lesion progression in offspring of hypercholesterolemic mothers was greater than in all other groups. At each time point, offspring of hypercholesterolemic mothers had 1.5- to 3-fold larger lesions than offspring of normocholesterolemic mothers (P<0.01), with the greatest absolute differences at 12 months. Maternal treatment reduced lesions by 19% to 53%, compared with offspring of untreated hypercholesterolemic mothers (P<0.01), with the greatest effect in the vitamin E groups. At 12 months, lesions in offspring of all vitamin E and cholestyramine-treated mothers were similar to those of normocholesterolemic mothers. Lipid peroxidation end-products in lesions and plasma showed analogous differences between groups as lesions (P<0.01). Thus, pathogenic programming in utero increases the susceptibility to atherogenic risk factors later in life and maternal intervention with cholesterol-lowering drugs or antioxidants reduce postnatal lipid peroxidation and atherosclerosis in their offspring.

  • intracranial arteries of human fetuses are more resistant to Hypercholesterolemia induced fatty streak formation than extracranial arteries
    Circulation, 1999
    Co-Authors: Claudio Napoli, Francesco P Darmiento, Giuseppe Palumbo, Filomena De Nigris, Joseph L Witztum, Wulf Palinski
    Abstract:

    Background —Atherosclerotic lesions in intracranial arteries occur later and are less extensive than in extracranial arteries. To investigate potential mechanisms responsible for this difference, in particular the atherogenic response to Hypercholesterolemia and LDL oxidation, we compared the extent of fatty streak formation and the composition of these very early lesions in intracranial arteries of human fetuses from normocholesterolemic and hypercholesterolemic mothers with those in extracranial arteries. Methods and Results —Lesions were quantified by computer-assisted image analysis of 30 oil red O–stained sections, each from the middle cerebral, basilar, and common carotid arteries and the abdominal aorta of human fetuses (spontaneous abortions and premature newborns who died within 12 hours of birth; both of fetal age 6.2±1.3 months) from 43 hypercholesterolemic mothers and 34 normocholesterolemic mothers. Macrophages, apolipoprotein B, and 2 epitopes of oxidized LDL in lesions were determined immunocytochemically. Activities of superoxide dismutase, catalase, and glutathione peroxidase in the arterial wall were also determined. Lesion numbers and sizes were dramatically greater in the abdominal aorta (area of the largest lesion per section: 66.5±10.9 ×10 3 μm 2 ) and the carotid (11.6±5.3 ×10 3 μm 2 ) than in the basilar and middle cerebral artery (0.4±0.1 and 0.8±0.2 ×10 3 μm 2 , respectively; P Conclusions —Exposure to Hypercholesterolemia during fetal development results in extensive formation of fatty streaks in extracranial but not intracranial arteries. The fact that such a difference in lesion formation occurs in the absence of many other atherogenic risk factors found later in life suggests that differences in the atherogenic response to Hypercholesterolemia are an important contributor to the slower onset of the disease in intracranial vessels in adults. Fetal arteries may allow elucidation of the mechanisms responsible, for example, better protection of intracranial arteries against free radical–mediated atherogenic processes.