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Biomedical subjects

Sridevi Devaraj

Publications and source records attributed to Sridevi Devaraj.

At least 19 recordsLinked to original sources
PubMed2003

C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis.

BACKGROUND: Inflammation plays a pivotal role in atherosclerosis. In addition to being a risk marker for cardiovascular disease, much recent data suggest that C-reactive protein (CRP) promotes atherogenesis via effects on monocytes and endothelial cells. The metabolic syndrome is associated with significantly elevated levels of CRP. Plasminogen activator inhibitor-1 (PAI-1), a marker of atherothrombosis, is also elevated in the metabolic syndrome and in diabetes, and endothelial cells are the major source of PAI-1. However, there are no studies examining the effect of CRP on PAI-1 in human aortic endothelial cells (HAECs). METHODS AND RESULTS: Incubation of HAECs with CRP results in a time- and dose-dependent increase in secreted PAI-1 antigen, PAI-1 activity, intracellular PAI-1 protein, and PAI-1 mRNA. CRP stabilizes PAI-1 mRNA. Inhibitors of endothelial NO synthase, blocking antibodies to interleukin-6 and an endothelin-1 receptor blocker, fail to attenuate the effect of CRP on PAI-1. CRP additionally increased PAI-1 under hyperglycemic conditions. CONCLUSIONS: This study makes the novel observation that CRP induces PAI-1 expression and activity in HAECs and thus has implications for both the metabolic syndrome and atherothrombosis.

Aorta↗
PubMed2003

Hyperhomocysteinemia in Asian Indians living in the United States.

Hyperhomocysteinemia has been reported in Asian Indians (people from Indian subcontinent) to be related to relatively low plasma levels of folate and vitamin B-12. However, a true ethnic-related characteristic has not been excluded. This study was done to determine whether Asian Indians have high plasma homocysteine compared with Caucasians in the United States in the era of folate fortification, and whether low vitamin B-12 or insulin resistance may account for possible interethnic differences in plasma homocysteine. A total of 227 Asian Indians (131 males and 96 females) and 155 Caucasians (66 males and 89 females) completed a questionnaire for medical, family, and personal history. They had height, weight, and blood pressure measured and fasting blood drawn for routine chemistry, TSH, plasma homocysteine, vitamin B-12, and folate. Oral glucose tolerance test and vitamin B-6 was measured in a subgroup of 66 Asian Indians (47 males and 19 females) and 63 Caucasians (33 males and 30 females). Asian Indians were found to have significantly higher plasma homocysteine than Caucasians (median of 12.6 and 8.0 micro mol/liter, P < 0.0001, respectively) and lower plasma concentrations of B-6 (median 49 vs. 70 nmol/liter; P = 0.05, respectively). Plasma folate was relatively high and similar in both ethnic groups. Plasma vitamin B-12 was significantly lower in Asian Indians than Caucasians (median of 204 vs. 320 pmol/liter, P < 0.0001, respectively). Vitamin B-12 correlated significantly with plasma homocysteine. When vitamin B-12 was between 150 and 379 pmol/liter, the regression curve between vitamin B-12 and homocysteine had significantly different slope in the two ethnic groups (P value < 0.05) and Asian Indians had significantly higher homocysteine for any level of vitamin B-12. Although insulin resistance, measured as insulin area under the curve by oral glucose tolerance test was higher in Asian Indians and correlated significantly with homocysteine, it did not explain inter-ethnic differences in plasma homocysteine in a multivariate analysis. We conclude that Asian Indians living in the United States have significant elevation of plasma homocysteine concentrations despite normal plasma folate. Lower plasma concentrations of vitamin B-12 and lower insulin sensitivity may contribute to this finding but only partially explained the ethnic-related hyperhomocysteinemia of the Asian Indians.

Adult↗
PubMed2003

Elevated plasma high-sensitivity C-reactive protein concentrations in Asian Indians living in the United States.

Proinflammatory state may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease observed in populations originating from the Indian subcontinent (Asian Indians). This study was conducted to evaluate whether nondiabetic Asian Indian men living in the United States manifest a proinflammatory state when compared with Caucasians of similar age and body fat content. We also compared the relationships between plasma high-sensitivity C-reactive protein (hs-CRP), a marker of low-grade inflammation, and various parameters of body composition and fat distribution and insulin sensitivity in Asian Indians and Caucasians. For this purpose, plasma hs-CRP, oral glucose tolerance test, and anthropometric measurements were conducted in 82 Asian Indian men and 55 Caucasian men of similar age. The two groups had similar body fat content and truncal skinfolds thickness. Asian Indians had higher insulin areas under the curve during oral glucose tolerance tests, indicating a greater insulin resistance. Asian Indians also manifested a significant elevation of plasma hs-CRP. We conclude that young, overtly healthy Asian Indian men have both greater insulin resistance and higher hs-CRP levels than do Caucasians. This difference cannot be explained by greater adiposity in Asian Indians and suggests that many Asian Indians have an underlying proinflammatory state that may contribute to their increased risk for both type 2 diabetes and cardiovascular disease.

Adipose Tissue↗
PubMed2002

Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells.

BACKGROUND: C-reactive protein (CRP), the prototypic marker of inflammation, has been shown to be an independent predictor of cardiovascular events. Endothelial nitric oxide synthase (eNOS) deficiency is a pivotal event in atherogenesis. METHODS AND RESULTS: We tested the effect of CRP on eNOS expression and bioactivity in cultured human aortic endothelial cells (HAECs). CRP decreased eNOS mRNA, protein abundance, and enzyme activity in HAECs. Furthermore, eNOS bioactivity assayed by cyclic GMP levels was significantly reduced by CRP. Preincubation of cells with CRP also significantly increased the adhesion of monocytes to HAECs. CONCLUSION: CRP causes a direct reduction in eNOS expression and bioactivity in HAECs, further supporting its role in atherogenesis.

Aorta↗
PubMed2002

Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile.

Pycnogenol (PYC), an extract of French maritime pine bark (Pinus pinaster), is a potent antioxidant with potential health benefits. Its bioavailabilty has previously been shown by urinary excretion studies of constituents and metabolites of PYC. The aim of this study was to test the effect of PYC supplementation on measures of oxidative stress and the lipid profile in humans. Twenty-five healthy subjects received PYC (150 mg/d) for 6 wk. Fasting blood was collected at baseline, after 3 and 6 wk of supplementation, and again after a 4-wk washout period. After 6 wk of supplementation with PYC, a significant increase in plasma polyphenol levels was detectable, which was reversed after the 4-wk washout phase. The antioxidant effect of PYC was demonstrated by a significant increase in oxygen radical absorbance capacity (ORAC) in plasma throughout the supplementation period (P < 0.05). The ORAC value returned to baseline after the 4-wk washout period. Moreover, in addition to its antioxidant effects, PYC significantly reduced LDL-cholesterol levels and increased HDL-cholesterol levels in plasma of two-thirds of the subjects. While the LDL changes reversed during washout, the HDL increase did not. There was no significant difference in LDL oxidizability or plasma lipid peroxides following PYC supplementation. Hence, following oral supplementation in humans, PYC significantly increases antioxidant capacity of plasma, as determined by ORAC, and exerts favorable effects on the lipid profile.

Administration, Oral↗
PubMed2002

Oxidative stress, alpha-tocopherol therapy, and atherosclerosis.

Atherosclerosis is the leading cause of morbidity and mortality in the United States. Evidence suggests that antioxidants, especially alpha-tocopherol (AT), have potential benefits with respect to cardiovascular disease. AT has been shown to decrease lipid peroxidation, to inhibit platelet adhesion, aggregation, and smooth muscle cell proliferation, to exert anti-inflammatory effects on monocytes, and to improve endothelial function. Low levels of AT are related to a higher incidence of cardiovascular disease and increased intakes appear to afford protection against cardiovascular disease. Although clinical trials with AT supplementation to date have been conflicting, the majority of evidence supports a benefit for AT supplementation in patients with pre-existing cardiovascular disease. Clearly, more clinical trials are required in individuals with increased oxidative stress before a definitive recommendation can be made with respect to AT supplementation in atherosclerosis.

Arteriosclerosis↗
PubMed2002

Autoantibodies to oxidized low-density lipoprotein in patients with type 2 diabetes mellitus.

BACKGROUND: Oxidation of low-density lipoprotein (LDL) is a crucial step in atherogenesis. There is an urgent need for direct measures of in vivo oxidative stress. Autoantibodies against oxidized low-density lipoprotein (Ab against Ox-LDL) are a direct measure of oxidative stress and predict cardiovascular disease. Our aim was to evaluate an ELISA for Ab against Ox-LDL in Type 2 diabetes, a condition with increased oxidative stress. METHODS: Ab against Ox-LDL were measured by ELISA and expressed as a ratio of Ox-LDL to native LDL (N-LDL). Samples were obtained from 45 Type 2 diabetic patients and 25 matched controls before and after supplementation with alpha tocopherol (AT, 1200 IU/day). RESULTS: The assay had good precision. While there was no interference with bilirubin and hemolysis, triglycerides 500 mg/dl increased antibody titer, which was abrogated by airfuging. Compared to controls, significantly increased titers of Ab against Ox-LDL were found in diabetics (diabetes mellitus Type 2) with macrovascular disease (DM2-MV), but not without macrovascular disease (DM2) (DM2: 1.32+/-0.33; DM2-MV: 1.48+/-0.44 vs. controls, 1.21+/-0.28; p<0.05). AT supplementation significantly decreased titers of Ab against Ox-LDL in both diabetic groups (p<0.01). CONCLUSION: This assay may serve as a future test for the assessment of cardiovascular risk especially in patients with increased oxidative stress.

Autoantibodies↗
PubMed2002

Comparison of the antioxidant effects of Concord grape juice flavonoids alpha-tocopherol on markers of oxidative stress in healthy adults.

BACKGROUND: Concord grape juice (CGJ) is a rich source of flavonoids, which have greater antioxidant efficacy in vitro than does alpha-tocopherol; however, the efficacies of flavonoids and alpha-tocopherol in vivo have not been compared. OBJECTIVE: We compared the in vivo antioxidant efficacy of CGJ with that of alpha-tocopherol in healthy adults. DESIGN: Subjects were randomly assigned to receive either 400 IU RRR-alpha-tocopherol/d (n = 17) or 10 mL CGJ. kg(-1). d(-1) (n = 15) for 2 wk. Serum oxygen radical absorbance capacity, plasma protein carbonyls, urinary F(2)-isoprostanes, and resistance of LDL to ex vivo oxidation were measured before and after supplementation as markers of antioxidant status and oxidative stress. RESULTS: After supplementation, plasma alpha-tocopherol increased 92% in subjects who received alpha-tocopherol (P < 0.001); plasma total and conjugated phenols increased 17% (P < 0.01) and 22% (P < 0.001), respectively, in subjects who received CGJ. There was a significant change in plasma triacylglycerols in both groups, but the concentrations were within the normal range. CGJ supplementation was associated with significantly higher triacylglycerols than was alpha-tocopherol supplementation. Both supplementation regimens significantly increased serum oxygen radical absorbance capacity (P < 0.001) and LDL lag time (P < 0.001) and significantly decreased the LDL oxidation rate (P < 0.01), with no significant difference in effectiveness. Protein carbonyl concentrations in native plasma decreased 20% after CGJ supplementation, which was a significantly different response than that after alpha-tocopherol supplementation (P < 0.05). CONCLUSIONS: In healthy adults, 10 mL CGJ. kg(-1). d(-1) increased serum antioxidant capacity and protected LDL against oxidation to an extent similar to that obtained with 400 IU alpha-tocopherol/d but decreased native plasma protein oxidation significantly more than did alpha-tocopherol. CGJ flavonoids are potent antioxidants that may protect against oxidative stress and reduce the risk of free radical damage and chronic diseases.

Adult↗
PubMed2002

Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans.

Flavonoids and related polyphenolics with antioxidant and anti-inflammatory activities may play a role in the prevention of cardiovascular disease by decreasing oxidative stress and inflammation. We wished to determine the effects of cocoa extract supplementation on markers of oxidative stress and inflammation. Healthy subjects (n = 25) were studied at baseline, after cocoa supplementation (36.9 g of dark chocolate bar and 30.95 g of cocoa powder drink) for 6 wk and after a 6-wk washout period. Fasting blood and early morning urine were collected at the three time points. Two indices of flavonoid intake, total phenols and oxygen radical absorbance capacity of plasma, were measured after an overnight fast. Neither was affected by supplementation. Measures of oxidative stress included copper-catalyzed LDL oxidation kinetics and urinary F(2) isoprostanes. LDL oxidizability was lower after chocolate supplementation as evidenced by a longer lag time (P < 0.05) of conjugated diene formation (101.0 +/- 20.7 min) compared with baseline (91.3 +/- 18.0 min) and washout (96.4 +/- 7.5 min) phases. There was no effect of chocolate on urinary F(2) isoprostane levels or on markers of inflammation including the whole-blood cytokines, interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha, high sensitivity C-reactive protein and P-selectin. In conclusion, cocoa products supplementation in humans affects LDL oxidizability, but not urinary F(2) isoprostanes or markers of inflammation.

Antioxidants↗
PubMed2002

Accelerated atherosclerosis, dyslipidemia, and oxidative stress in end-stage renal disease.

Premature atherosclerosis is a major cause of morbidity and mortality in end-stage renal disease patients. Dyslipidemia and increased oxidative stress contribute to premature atherogenesis in these patients. The dyslipidemia of end-stage renal disease consists of both quantitative and qualitative abnormalities in serum lipoproteins. Qualitative changes include hypertriglyceridemia (increased remnant lipoproteins), low high-density lipoprotein-cholesterol, and increased lipoprotein (a). In addition to quantitative changes, lipoproteins in end-stage renal disease undergo compositional and qualitative changes that make them pro-atherogenic, such as various modifications of apolipoprotein B, including oxidation, and modification by advanced glycation end-products. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and low-dose fibrates could be effective therapies for lipid disorders. The best evidence for increased oxidative stress in end-stage renal disease is the demonstration of increased plasma F2-isoprostanes. Confirmation of the positive findings with high-dose alpha-tocopherol in the Secondary Prevention with Antioxidants of Cardiovascular Disease in End-stage Renal Disease Study is urgently needed. Clinical trials with statins and other drugs that improve dyslipidemia also need to be undertaken. These therapies could clearly lead to a reduction in cardiovascular morbidity and mortality in these patients.

Arteriosclerosis↗
PubMed2002

Modulation of monocyte-macrophage function with alpha-tocopherol: implications for atherosclerosis.

Cardiovascular disease is the leading cause of morbidity and mortality in the Western world. Monocyte-macrophages are crucial cells in atherogenesis. Several lines of evidence suggest that antioxidants, especially alpha-tocopherol, have beneficial effects with regard to cardiovascular disease. Alpha-tocopherol has beneficial effects on cell functions that are pivotal in atherogenesis. Alpha-tocopherol inhibits platelet aggregation and proinflammatory activity of monocytes. In vitro data also support an effect of alpha-tocopherol on smooth muscle cell proliferation and endothelial function. Finally, recent data support an effect of alpha-tocopherol on macrophage function. The mounting evidence from in vitro and in vivo studies provides a sound scientific basis for alpha-tocopherol supplementation. Further clinical trials are required, however, before a definitive recommendation can be made for primary and secondary prevention of heart disease.

Antioxidants↗
PubMed2002

Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha.

Diabetes is a major risk factor for premature atherosclerosis, and oxidative stress appears to be an important mechanism. Previously, we showed that diabetic monocytes produce increased superoxide anion (O(2)(-)), and alpha-tocopherol (AT) supplementation decreases this. The aim of this study was to elucidate the mechanism(s) of O(2)(-) release and inhibition by AT under hyperglycemic (HG) conditions in monocytes. O(2)(-) release, protein kinase C (PKC) activity, and translocation of PKC-alpha and -betaII and p47phox were increased in THP-1 cells (human monocytic cell line) under HG (15 mmol/l glucose) conditions, whereas AT supplementation inhibited these changes. AT, NADPH oxidase inhibitors (apocynin and diphenyleneiodonium chloride [DPI]), and an inhibitor to PKC-alpha and other isoforms (2,2',3,3',4,4'-hexahydroxy-1,1'-biphenyl-6,6'-dimethanol dimethyl ether [HBDDE]) but not PKC-beta II (LY379196) decreased O(2)(-) release and p47phox translocation. Antisense oligodeoxynucleotides to PKC-alpha and p47phox but not to PKC-betaII inhibited HG-induced O(2)(-) release and p47phox translocation in THP-1 cells. Under HG conditions, reactive oxygen species release from monocytes was not inhibited by agents affecting mitochondrial metabolism but was inhibited in human endothelial cells. We conclude that under HG conditions, monocytic O(2)(-) release is dependent on NADPH oxidase activity but not the mitochondrial respiratory chain; HG-induced O(2)(-) release is triggered by PKC-alpha, and AT inhibits O(2)(-) release via inhibition of PKC-alpha.

Acetophenones↗
PubMed2002

alpha-Tocopherol supplementation decreases plasminogen activator inhibitor-1 and P-selectin levels in type 2 diabetic patients.

OBJECTIVE: Type 2 diabetic subjects have an increased propensity to premature atherothrombosis. alpha-Tocopherol (AT), a potent antioxidant, has anti-inflammatory properties at high doses. The aim of the study was to test the effect of natural (RRR)-AT supplementation (1,200 IU/day) on markers of thrombosis, plasminogen activator inhibitor-1 (PAI-1), and soluble P-selectin (sP-selectin) in type 2 diabetic patients with and without macrovascular complications (MVCs) compared with matched control subjects. RESEARCH DESIGN AND METHODS: The volunteers comprised type 2 diabetic patients with (n=23) and without (n=24) MVCs and matched control subjects (n=25). Plasma levels of PAI-1 and P-selectin were assayed at baseline, after 3 months of supplementation, and after a 2-month washout phase. RESULTS: Both diabetic groups had significantly increased levels of PAI-1 compared with control subjects (P < 0.025), whereas only type 2 diabetic patients with MVCs had significantly elevated levels of sP-selectin compared with control subjects. AT supplementation significantly lowered levels of PAI-1 and sP-selectin in all three groups. The reduction in PAI-1 levels with AT supplementation was significantly greater in type 2 diabetic patients with MVCs than in those without MVCs (P=0.005). CONCLUSIONS: Thus, AT therapy decreases markers of thrombosis in diabetic patients and control subjects and could be an adjunctive therapy in the prevention of atherosclerosis.

Antioxidants↗